Toad poisoning in dogs is quite common. Dogs are predators, they often bite toads, getting poisoned by the poison that the toads secrete. This highly toxic substance is usually absorbed through the gingival membranes, but can also enter the animal's body through the eyes, causing vision problems. In the absence of urgent medical care, the outcome can be fatal.
The toads that most commonly affect domestic animals are the Colorado river toad (Bufo alvarius) and the cane toad (Bufo marinus). Most cases of poisoning occur during the warmest and wettest months, when toads are most active. Usually animals come into contact with toads in the early morning or evening. These varieties of toads are omnivorous, they feed on living things (insects and small rodents) and can also eat food left outside for pets. In this regard, pets often encounter these amphibians while eating. That is why food is not recommended to be left outside in places where poisonous toads live.
Symptoms and types
Symptoms usually appear within seconds of contact with the toad and may include the following:
- whining or other sounds;
- the dog rubs its mouth and/or eyes with its paw;
- severe salivation;
- discoloration of the gums (may become inflamed or fade);
- labored breathing;
- instability;
- convulsive seizures;
- elevated temperature;
- collapse.
Causes
life in the habitat of poisonous toads and coming into contact with them;
more common in dogs that spend a lot of time outdoors.
Diagnostics
Toad poisoning is an emergency situation that can lead to death. This poisoning requires immediate medical attention. You will need to contact the veterinarian on duty, provide him with a detailed medical history, describe the symptoms, and let him know how likely the dog was to have been exposed to the poisonous toad.
The doctor will conduct a complete physical examination of the animal, take a blood and urine test. The results of these tests are usually normal, with the exception of high potassium levels (hyperkalemia). The dog may also experience irregular heartbeats. If the veterinarian has time to do an electrocardiogram (ECG), this usually confirms an irregular heart rhythm due to toad venom poisoning.
Treatment
Poisoning with toad venom is very often fatal. Time plays a vital role in the survival of an animal. If you suspect that your animal is suffering from toad poisoning, take it to the nearest veterinary clinic immediately for emergency medical attention.
The first step in treatment is to rinse the dog's mouth with water for 5-10 minutes to prevent further absorption of the venom through the gingival membranes. To maintain a normal body temperature, it may be necessary to place the animal in a cool bath. Irregular heart rhythm is a common symptom, so the veterinarian will monitor the heart's ability to function normally and its response to treatment with an ECG. To control the heart rate, as well as in order to reduce the amount of saliva secreted by the body in response to intoxication, the doctor may apply certain medications. If the dog is clearly in severe pain, the veterinarian may administer anesthesia to relieve the symptoms.
Further observation
The condition of the dog will need to be monitored until complete recovery. Your veterinarian will continuously monitor your heart rate with an ECG. If treatment was started before a large amount of the toxin entered the body (within 30 minutes of exposure to the poison), the animal would have a good chance of survival.
Amphibian toxicity
Since ancient times, the poisonousness of some species of toads and frogs has been known. The symptoms of poisoning with toad venom and the possibility of using it to treat certain diseases have been described. In ancient Rome, toads were also used for poisoning, although not always successfully. Forestus described the story of a woman in Rome who decided to poison her husband who was suffering from edema. To do this, she sprinkled powder of dried and crushed toads into his food, but instead of dying, her husband soon cured from swelling.
Not all amphibians are venomous and not all equally venomous. The most poisonous are Dart frogs And leaf climbers, whose poison kills large mammals on the spot. Amphibian venoms have a wide spectrum of biological activity, and some of them, such as toad venom, are of medical interest.
Amphibians belong to unarmed actively poisonous animals, since their poisonous apparatus is devoid of the injuring devices necessary for the active introduction of poison into the body of the enemy. The diet of amphibians is dominated by small invertebrates, so they have no need for fangs or spines. The secret of the mucous glands of amphibians has not only a strong toxic effect, but also protects moist skin of amphibians from colonization by microorganisms. The poison is produced by the skin through parotids, which probably formed from poisonous alveolar glands. In amphibians, toxic steroidal alkaloids, which are not destroyed in the body of the victim by digestive enzymes when ingested through the mouth, and, therefore, are capable of exerting a toxic effect.
Toads(Bombina) . The mucus secreted by the skin glands contains a poisonous secret. frinolecin which causes acute burning sensation when it comes into contact with the oral mucosa. The secret secreted by their skin, getting on the mucous membranes, causes severe irritation, and sometimes poisoning. Ordinary frogs, planted in the same jar with toads, die after a few hours. Young individuals, having got used to new conditions, do not emit poisonous mucus, even if they are picked up.
For humans, the poison of the toads is not very dangerous. When it comes into contact with the mucous membranes, pain, burning sensation is felt, in some cases - chills and headache. In animals, short-term excitation and increased respiration are observed, followed by long-term, up to the onset of death, depression.
common spadefoot(Pelobatesfuscus Laurenti). The poisonous secretion is toxic to small animals. In humans, it causes irritation of the mucous membranes. Chemical composition and mechanisms of action practically not studied.
toads(Bufonidae, Bufo). Many toads have large parotid venom glands behind their eyes on the dorsal side of their heads. parotids, and along the entire back and top of the head there are many small poisonous glands. Each parotid contains up to 0.07 g of poisonous secretion. When a predator attacks, small poisonous glands are the first to work, reflexively secreting a secret with a sharp specific smell, a bitter taste that causes burning and vomiting. The secret of the parotids, irritating the mucous membrane, forces the predator that has seized the toad to spit it out. The most powerful poison is possessed by a toad, aha - Bufo marinus, whose poison power is so great that a dog that grabs a toad quickly dies.
In the evening, before going hunting, the toads carefully rub their backs with their paws, squeezing out the poison in order, apparently, to insure themselves against possible attacks in advance. When the gland is squeezed, the epithelial plug is pushed out and the toxic secret can with force thrown out, sometimes at a distance of up to 1 m.
Toad venom is obtained by squeezing out parotids with soft-jawed tweezers, or by passing a glass plate over the toad's back. Freshly obtained toad venom is viscous white liquid with a characteristic odour. When dried, it turns into yellowish-brown plates, which retain their toxicity and physiological activity for many years. IN venom composition include tryptamine, serotonin, bufotenin, catecholamine (in particular adrenaline), etc. In non-toxic doses, toad venom has anthelmintic, anti-shock, radioprotective and antitumor effects. The cardiotropic properties of the poison allow us to consider it as a promising source of new drugs.
On the skin South American toad species Bufo marinus ( toad, yeah, sea toad) stands out hallucinogenic enzyme. Theoretically, if you lick a toad, you can get an effect close to the effects of the drug LSD. The glands of the toad do indeed contain bufotenin, a hallucinogen that causes intoxication, short-term euphoria. According to some evidence, Mayan and Aztec priests could use Bufo marinus in their rituals, but historical documents have preserved very little evidence of how such an effect is achieved. Toad venom was used by the Choco Indians of western Colombia to lubricate arrowheads, by the Chinese, who condensed the poison into ballet flats and used it as a medicine as a medicine, as well as a poison in the political sphere.
Poisoning of animals, most often dogs, is characterized by profuse salivation, tachycardia, arrhythmias, pulmonary edema, convulsions, and, in severe cases, death. In humans, contact with poison on the mucous membranes, especially the eyes, causes severe irritation, pain, conjunctivitis and keratitis. Remove the poisonous secret by copious washing.
Salamander(Salamandra). fire salamander has long been considered a mystical and dangerous animal. In addition to the widespread belief that she could live in fire without harm to herself, her extreme poisonousness was also known. Pliny the Elder (23-79 AD) wrote: "The most terrible of all animals is the salamander. Others bite at least individual people and do not kill many at once ... but the salamander can destroy an entire people no one will notice where the misfortune came from. If a salamander climbs a tree, all the fruits on it become poisonous ... If a salamander touches a leaf on which bread is baked, then the bread becomes poisonous; falling into a stream, it poisons the water. If it touches any part of the body, even the tip of the finger, then all the hair on the body falls out. However, some animals, such as pigs, eat this terrible creature, because everyone has enemies. "
Back in 1860, it was found that the active principle of salamander venom is alkaloids, and in 1930 their steroid structure was determined. Fortunately for researchers and salamanders, comparatively large amounts of alkaloids could be obtained from the parotid glands of these amphibians, unlike, for example, dart frogs (Dendrobates). The main alkaloid was named samandarine, and a total of 9 alkaloids with similar structures were isolated. Characteristic of most samandarine alkaloids is the presence of an oxazolidine ring.
Salamander venom for humans poses no danger, except for special cases (obtaining poison, etc.). In animals poisoned by salamander venom, anxiety, mydriasis, and the development of periodic convulsive seizures are observed. Under the influence of poison in animals, reflexes progressively weaken, up to complete disappearance, breathing becomes weak, cardiac arrhythmias are observed. In the terminal phase, paralysis occurs, especially of the hind limbs. As a rule, death occurs within 5 hours of respiratory arrest. At autopsy, hemorrhages are noted in the lungs, heart, and brain.
Poison is very active absorbed through intact mucous membranes and with this method of administration causes mammals. The convulsive syndrome characteristic of salamander venom is effectively prevented and relieved by drugs of the benzodiazepine series (seduxen, etc.).
Chemical composition and mechanism of action of the poison. The composition of the poison includes steroidal alkaloids: samandarin, samandaron, cycloneosamandaron, etc., as well as serotonin and hemolytic proteins.
Samandarin quite toxic, its lethal dose for mice is about 70 mcg. He belongs to the group neurotoxins and causes convulsions, respiratory distress, cardiac arrhythmias, and partial paralysis. From a pharmacological point of view, samandarines are considered as potential local anesthetics. In addition, they have antimicrobial activity. Salamanders placed in an aquarium with guppies or carps cause their death. A nimble lizard that has bitten a salamander in the region of parotid dies after 30 seconds, and an ordinary viper after 4 minutes.
salamanders themselves sensitive to their alkaloids (when they enter the bloodstream). Samandarine alkaloids have been found in only two species of salamander - the European spotted salamander (Salamandra salamandra) and the alpine Salamandra atra. Alkaloids similar in structure to those of these amphibians have not been found anywhere else in nature. Salamanders synthesize alkaloids on their own and their content does not decrease in amphibians in the terrarium for at least three generations.
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The planet Earth is inhabited by a wide variety of poisonous creatures. Among them, a special place is occupied by tailless amphibians - frogs and toads. These are primary poisonous animals, that is, their poison-producing glands are given to them by nature and poisonousness is their protection. At the same time, these are passive-poisonous animals, since they do not have a device that actively injures the victim - teeth, spikes, etc.
How is the poisonous apparatus of amphibians arranged?
In the process of evolution, amphibians developed glands that secrete skin secretions. In toads, the suprascapular areas of the skin are especially important, having the shape of ovals and protruding above the general surface of the skin. These are suprascapular, or parotid glands, located on the sides of the head and secreting a poisonous secret.
The suprascapular skin glands of toads have a structure typical of all amphibians - cellular, alveolar. Each such gland on average consists of 30-35 alveolar lobules. Alveolar lobule - a section of the gland containing a group of alveoli. The alveoli have their own excretory duct that goes to the surface of the skin. When the toad is calm, it is usually closed with a plug of epithelial cells. The surface of the alveoli of the poisonous gland is lined from above with glandular cells that produce a poisonous secret, which from them enters the cavity of the alveolar vesicle, where it remains until the moment when there is a need for defense. Fully formed poisonous glands of an amphibian contain up to 70 mg of poisonous secretion.
Unlike the suprascapular glands, ordinary small skin glands that secrete mucus have open excretory ducts. Through them, the mucous secretion enters the surface of the skin, and, on the one hand, moisturizes it, and on the other, is a deterrent.
The work of the suprascapular glands is simple. If, for example, a poisonous toad is seized by a dog, it will immediately spit it out, and it is good if it remains alive. When the gland is squeezed by the jaws, the poisonous secret pushes the epithelial plugs out of the alveolar ducts and enters the dog's oral cavity, and from there into the pharynx. In the end, general severe poisoning may occur.
The well-known biologist-naturalist F. Talyzin described a case when a live toad was thrown into a cage with a hungry hawk. Naturally, the bird immediately grabbed it and began to peck. However, she suddenly recoiled sharply away, huddled in the corner of the cage, where for some time she sat ruffled, and died a few minutes later.
For the toads themselves, the poison is not dangerous, on the contrary, it is a reliable means of protection. No one dares to feast on such prey, except perhaps a ringed snake or a gigantic salamander - for them the poison of a toad is not dangerous.
Poisonous tailless amphibians of Russia
In the European part of Russia and in the south, up to the Black Sea, as well as in the Crimea, you can meet amphibians from the spadefoot family (Pelobatidae). The pungent smell of the poisonous secretion of these amphibians resembles the smell of garlic. The venom of the spadefoot is more toxic than that of, say, the green or gray toad.
Common spadefoot (Pelobates fuscus)The habitat of the green toad (Bufo viridis) extends from North Africa to Asia and Siberia, running through almost the entire territory of Europe. It is found everywhere at the southern borders of the European part of Russia and in Western Siberia. The skin of the green toad has poisonous glands, but this is dangerous only for its enemies. For other animals and humans, the poison is not dangerous.
Green toad (Bufo viridis) In addition to the green toad, the gray or common toad (Bufo bufo) is widespread in Russia. It is dangerous for pets - dogs, cats, and to a lesser extent for humans. The poison of this amphibian, accidentally caught on the mucous membrane of the eye or mouth, causes inflammation and severe pain.
Common toad (Bufo bufo) In the European part of Russia, another amphibian lives - the red-bellied toad. It is also distributed in Denmark and from southern Sweden to Austria, Hungary, Bulgaria, and Romania. From above it is dark gray, and the belly is bluish-black, with large bright orange spots (the so-called deterrent coloration). Bright spots sharply distinguish the toad against a green background of grass and, as it were, warn that this frog is poisonous and should not be touched. In case of danger, if the toad does not have time to hide in the pond, it takes a characteristic pose: it arches its head up, puts its front legs behind its back and puts forward its brightly colored spotted belly, thereby demonstrating its immunity. And oddly enough, it usually works! But if this does not scare away a particularly stubborn predator, the fireball emits a poisonous secret that is more poisonous than the secret of the spadefoot. Toad venom, like garlic venom, has a pungent odor, causing watery eyes, sneezing, and pain if it comes into contact with the skin. You can learn more about this amphibian from the article.
Fans of keeping red-bellied toads at home need to know that they should never be placed in an aquarium with other amphibians, such as newts - tailed amphibians or other frogs. From the proximity to the toad they can die.
Red-bellied fire-bellied toad (Bombina bombina) Dart frogs - especially poisonous frogs
But not only toads have poisonous skin glands. The most dangerous for humans are the frogs of the tree frog family (Dendrobatidae). The family includes about 120 species and almost all of them have poisonous glands that produce highly toxic substances.
Exotic lovers grow poison dart frogs in terrariums. After all, these tiny amphibians (their body length does not exceed 3 cm) are unusually beautiful, and their color can be very diverse - blue, red, green, golden, polka dot, striped ...
But how are these terribly poisonous frogs kept in terrariums, you ask? The thing is that the toxicity of these creatures, as a rule, is due to their diet: in nature, they eat small ants and termites and accumulate their poison. In the conditions of a terrarium, devoid of "poisonous nourishment", the frogs soon become practically safe.
Reticulated dart frog (Ranitomeya reticulata) The family of poison dart frogs includes 9 genera, among which the genus of leaf climbing frogs is distinguished.
In the jungles of South America and Colombia, a tiny frog lives only 2-3 cm long and weighs 1 gram. She can climb trees, sit on leaves. It is called the terrible leaf climber (Phyllobates terribilis), or "kokoe" (this name was given to her by the locals). Kokoe is brightly colored and quite attractive, but it is better not to touch it. The skin glands of the leaf climber secrete poison, which is a mortal danger for both large animals and humans. A tiny scratch on the skin is enough for the poison to get there to cause a quick death. The terrible leaf climber, as if knowing that he has nothing to fear, does not hide, like his relatives, but calmly moves in broad daylight in the tropical forests of Guiana and Brazil. These tiny frogs don't need large bodies of water. They have enough water accumulated on the plants after the rain. Their tadpoles also develop here.
Terrible leaf climber (Phyllobates terribilis) The poison secreted by the skin glands of leaf climbers has long been used by the Indians to lubricate arrowheads. A small scratch inflicted by such an arrow is enough for the victim to die. Before touching such a frog, the Indians will definitely wrap their hands in leaves.
Since the “kokoe” frog is very small, it is almost impossible to find it among the dense greenery of the rainforest. In order to catch her, the Indians, who are able to perfectly imitate the inhabitants of the tropical forests, lure her out by imitating the cry of this frog. They long and patiently make sounds familiar to her, and listen for an answering cry. When the catchers determine the place where the amphibian is located, they catch it.
It has been estimated that the poison of one frog is enough to turn at least 50 arrowheads into deadly weapons.
The symptoms of poisoning with the poison of a terrible leaf climber resemble the symptoms when the juice of one of the plants growing in the tropical forests of the same regions gets into the wound. This plant is called curare, and the effect of the poison on the body is curariform due to its similarity with the action of the juice of this plant. The poison used to treat arrows is called "deadly poison". It acts very quickly, paralyzing the respiratory muscles, as a result, the victim dies from respiratory arrest.
Golden leaf climber (Phyllobates aurotaenia) Anuran amphibian venom
In general, the poison of frogs and toads is primarily a protein, which includes highly active compounds, enzymes, catalysts, etc. It contains chemicals that act on the nervous system, mainly the peripheral one, as well as proteins that cause the destruction of erythrocytes - red blood cells. The composition of the poison contains substances that selectively act on the heart.
Interestingly, these toxins have a special biological significance for the amphibians themselves. In "cocoe", which has a bright, defiant color that repels predators, the poison is exceptionally strong in its action. Frogs, on the other hand, are quite close in kinship to cocoe, but have a calm, inconspicuous color, and are generally devoid of a poisonous secret.
Etc the absence, or, conversely, the absence of certain substances in the skin of frogs depends on the place and conditions of their habitat. For example, amphibians that spend a lot of time on land have chemical components that can protect them in a terrestrial environment, unlike animals that prefer a longer aquatic lifestyle. It is interesting that the suprascapular glands of toads contain components in the poison that have a cardiotoxic orientation, i.e. acting primarily on the heart. Apparently, this feature of their poison is due to the terrestrial way of life and serves as a defense against predators attacking them. Even snakes will not eat a brightly colored toad, and if they grab it, they will try to throw it back. And this is despite the fact that many snakes have their own venom glands and have a certain natural immunity to poison.
The poison of tiny leaf climbers is sometimes dangerous for the frogs themselves. It is so strong in its action that, accidentally hitting a scratch on their skin, it can kill the frog itself. Apparently, the frogs that produce it are not affected by the poison under normal conditions of life. This is due to the fact that the cells producing the poison are well isolated from other tissues and the toxin cannot spread throughout the body “cocoe”.
There are practically no antidotes against leaf climber venom. The skin of an adult frog less than 50 mm long contains a very toxic substance - batrachotoxin, first isolated from the venom of the Colombian frog. Batrachotoxin is a chemical compound found in the skin venom of five frog species found in southern Central America and northwestern South America. At present, scientists have been able to artificially obtain this substance in the laboratory, and it is not inferior to natural in terms of toxic properties.
What happens when frogs and toads are poisoned?
The venom of tailless amphibians acts mainly on the circulatory and nervous systems and the heart. Of course, in order to be poisoned, say, with the poison of a toad, it must be taken into the mouth. Naturally, not a single normal person will do this, but poisoning with the poison of a terrible leaf climber is known. It is enough to take an amphibian with bare hands, and if there are cuts, abrasions and cracks on the skin, this can lead to severe poisoning and even death. Just imagine the state of a person when, as a result of the action of poison on the neuromuscular system, breathing begins to weaken. Inhalation becomes shallow, superficial. Gradually there is a lack of oxygen, the victim begins to suffocate. The heart and brain are also catastrophically lacking oxygen, convulsions occur, and then death from respiratory arrest.
The mechanism of action of leaf climber poison is as follows. On the border of the nerve and muscle there is a small special plate that has the properties of both nervous tissue and muscle, so it was called the neuromuscular synapse, or connection. Intercostal muscles also have such plates, which, together with the diaphragm, move air when inhaling into the lungs and when exhaling outward, i.e. carry out the process of respiration. It is on these plates that the action of the poison “cocoe” is directed. Turning them off from work, the poison thereby stops the transmission of a signal from the nerve to the muscle. Naturally, the signal cannot pass through the disconnected plate; as a result, the muscles do not receive a signal from the nervous system about the beginning of the contraction and also stop working, i.e. breathing stops.
There are isolated cases of human death from toad venom. One of these cases occurred through the fault of a healer, who advised the patient to get rid of a toothache in a very peculiar way: take a dried toad skin into his mouth and press it to the gum. This advice cost a man his life. Experts are well aware that in the dried skin of a toad, poison can persist for up to ten years, practically without losing its properties.
In contact with
Medicinal amphibians
It has now been established that among amphibians, toads can be attributed to medicinal animals. Wet warty skin, large mouth, bulging eyes have always evoked superstitious fear and disgust for these animals among the people. Since ancient times, they have been companions of witches and sorcerers and have served as a means of magic healers. The most studied representative of these ugly warty animals was named by C. Linnaeus Bufo bufo L.
Three types of toads live in the European part of the USSR: terrestrial, reed and gray (common). The latter is the most common and is larger than the green and reed.
It has long been observed that the skin secretion of toads is a poison to animals. Since the introduction of toads from South America to protect crops from pests in Australia, dingoes have often been observed dying after eating them. The same thing happened with Australian snakes. Academician P.S. Pallas wrote that his “hunting dog, after biting a toad, became seriously ill and died. Before that, after hunting for toads, she had swollen lips. In dogs that do not hunt, the smell of the skin of toads is disgusting. So, for example, A. Bram wrote: “One has only to hold a toad in front of the nose of well-bred dogs, as one wrinkles its nose and forehead skin and turns its head away, the other tucks its tail and nothing can force it to come closer again.”
There are descriptions of poisoning with toad venom in humans. The famous French physician Ambroise Pare wrote in 1575: “Not far from Toulouse, two merchants, while walking in the garden, picked sage leaves and put them in wine. After drinking the wine, they soon felt dizzy and fainted; vomiting and cold sweat appeared, the pulse disappeared, and death quickly occurred. The judicial investigation established that in the place of the garden where the sage grew, there were a lot of toads; hence it was concluded that the poisoning followed from the poison of the toads that fell on the indicated plant. There have been cases of poisoning of people in Argentina when they put the skin of a toad behind their cheeks to treat a toothache. After the pain subsided, the patient fell asleep, and by morning he was dead.
For medicinal purposes, toad venom has been used for a long time. Powder obtained from toad skins in the form of smooth round dark brown scales was used in China under the name "Chang-Su", and in Japan - "Sen-Co". Inside it was used for dropsy, to improve cardiac activity, and externally in the form of cakes as a remedy for toothache, inflammation of the paranasal sinuses and bleeding gums.
In the Hutsulshchyna, in order to get rid of the "pasnitsa" (it is not known what disease was meant by this name), the green toad was insisted in water, and it was recommended to drink the infusion in small portions. On the
They rubbed the legs of the Boykovshchina with a toad, believing that they would never get sick.
For therapeutic purposes, not only toad poison is used, but also meat. At the Institute of Oriental Medicine of the Socialist Republic of Vietnam, it is prescribed to children with dystrophy in the form of Com Cae tablets, which also include yolk and dried banana. Chinese doctors recommend using toad meat in the treatment of bronchial asthma and as a tonic.
At present, a preparation from the poison of Chinese toads called "mapin" (according to the Japanese pharmacopoeia of 1951) is used for therapeutic purposes in many countries of the East. In 1965, Japanese scientists Iwatsuki, Yusa, and Kataoka reported the successful clinical use of components isolated from toad venom.
S. V. Pigulevsky cites the information of researchers Growth and Paul, according to which toad venom was widely used in the treatment of dropsy before the introduction of foxglove. It was also used to poison arrows. One of the first researchers of the nature of toad venom, the famous French physiologist Claude Bernard wrote over 400 years ago that "the poison resists the action of heat, it is soluble in alcohol and that, in a word, it is as resistant as the poison of arrows." “Here, for example, are the arrows given to me by Mr. Busengo - they are from South America. I don't know at all what the nature of the poison they contain is. It is not curare, as was supposed, because its toxic effect is on the muscles, not on the nerves. I am inclined to think that it is the poison of the toads, which abounds in the country where these arrows are made; the venom of toads is indeed a very energetic effect on the muscle fiber.
Subsequent researchers found that the natives of South America extract the poison of the skin glands of toads by boiling, adding poisonous plants to the boiling solution to enhance its toxic effect.
The mass of dried poison from one toad is 16 mg in males and 27 mg in females. In the form of white foam, it flows freely from the skin glands to the surface of the body. From the parotid glands (parotid), it can be sprayed with force at a distance of up to a meter. According to V. I. Zakharov, toad venom in dilutions of 1: 100 and 1: 1000 after 20 minutes causes paralysis of the limbs and death of ticks. Toad venom, injected into the blood of small birds and lizards, kills them in a few minutes. Rabbits, guinea pigs and dogs die in less than an hour.
In 1935, the Soviet researcher F. Talyzin caught 16 green toads in Kyrgyzstan, removed their skin, dried it and stored it until 1965, after which he studied its toxic properties. It was found that after 30 years of storage in relatively unfavorable conditions of humidity and temperature, toad venom almost does not lose its characteristic toxic properties.
Currently, the most studied compound isolated from toad venom is bufotoxin, an ester of the steroid bufogenin with the dipeptide suberylarginine,
Bufotoxin |
Like many other animal poisons, toad toxin contains phospholipase A.
In 1978, B.N. Orlov and V.N. Krylov compiled a table in which the physiologically active substances of toad venom are represented by two groups of chemical compounds
Toad venom contains up to 5 - 7% of adrenaline. It should be noted that in the human adrenal glands, its concentration is four times less. The high content of this compound, which has a vasoconstrictive effect, can explain the use of the Chinese drug "Chang-Su" as an external hemostatic agent.
It should be noted that the composition of the venom of different species of toads has certain quantitative fluctuations, and the isolated bufotoxins differ, as a rule, in the radicals of the steroid part of the molecules.
Like other steroids, toad venom is synthesized in the body from cholesterol.
Steroids |
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| Catecholamines | indole derivatives | Cardiotonic substances | Sterols | |||
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Adrenalin |
Serotonin, tryptamine |
Bufotenins | Bufogenins (free genins) | Bufotoxins (related genins) |
Cholesterol, ergosterol, sitosterol, etc. |
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Bufotenin, bufotenidine, bufothionine, etc. |
Bufadienolides | Cardenolides |
Bufotoxin, gamabufotoxin, cinobufotoxin, etc. |
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Bufalin, bufotalin, gamabufotalin, cynobufagin, etc. |
Oleandrigenin, etc. |
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In official medicine, reports of its medicinal properties appeared at the end of the last century, when a woman addressed the Italian doctor S. Staderini with complaints of pain in her eye. She said that she grabbed a toad with her fireplace tongs, which got into the room. At that moment, the toad violently sprayed poison from the parotid glands, a drop of which fell into the eye. At first, the woman felt pain, then there was a loss of sensitivity. This case forced Staderini to conduct animal studies and study the analgesic properties of toad venom. A 1% solution, unlike a concentrated solution, did not cause severe eye irritation, while at the same time providing long-term anesthesia. After animal studies, he applied the new anesthetic to humans and published his observations in 1888. According to Staderini, an aqueous solution of toad venom is capable of displacing cocaine from practice, which at that time was often used for local anesthesia, in terms of the effectiveness of anesthesia.
The cardiotropic effect of toad venom was studied by N. P. Kravkov, F. F. Talyzin, V. I. Zakharov and the Japanese scientist Okada. The effect of various doses of the poison of common toads on the heart of warm-blooded animals was studied in 1974 by B. N. Orlov and V. N. Krylov. These authors found that toad venom had a pronounced stimulating effect on the isolated heart of a cat. At the same time, the effect was manifested in a wide range of dilutions - from 1: 5000 to 1: 1000000 g/ml. The same stimulating effect was observed when the poison was introduced into the body - there was an increase in the strength and frequency of heart contractions, an increase in pulse pressure, a decrease in the systological index, etc. Probably, the effect of the poison is associated with the stimulation of tissue metabolism in the heart muscle, since this effect was also observed on isolated heart and blockade of nerve endings with chemicals. In addition, the poison, apparently, has a direct effect on the conduction system of the heart and the nodes of automatism. This can be judged, but the fact that the administration of poison in large doses caused atrioventricular blockade and the appearance of a ventricular rhythm, arrhythmias were observed. This scientifically confirmed the use of toad venom in folk medicine for heart failure. After the systematic introduction of toad venom, an increase in blood pressure is observed due to an increase in heart contractions, as well as a decrease in the rhythm of cardiac activity. Its action is close to the action of strophanthin "K".
It was also found that toad venom stimulates breathing, restores it even after a complete stop.
V. I. Zakharov used the poison of toads in the experimental therapy of radiation injuries. The introduction of toad venom to rats immediately after irradiation had a powerful stimulating effect on hematopoiesis, accompanied by an increase in the production of leukocytes and platelets, as well as an increase in the phagocytic activity of leukocytes. An increase in animal survival was observed. The introduction of poison after irradiation also prevented the development of vascular damage and the occurrence of hemorrhages.
According to V. I. Zakharov, toad venom at a dilution of 1: 1000, 1: 2000 and 1: 4000 kills helminths of humans and animals in vitro: liver fluke within 30 minutes, pumpkin tapeworm - 37 - 48 minutes, unarmed tapeworm - 15 – 45 min. He also made experiments on the deworming of dogs and mares. After the application of the poison, a laxative effect was observed due to a sharp irritation of the intestines and a laxative was not prescribed. However, the author notes: "The emetic action of toad venom limits its use as an antihelminthic." It was also possible to establish that toad venom accelerates the healing process of wounds in experimental animals. There is a description of another property of toad venom, which is given by the American professor of homeopathy E. A. Farrington. In his lectures given at the Hahnemann Medical College in Philadelphia, he points out that one of the representatives of the toads of South America secretes on the surface of the body "an oily substance, considered poisonous. Local women, when they are too bothered by their husbands, mix this secretion into their drink to cause impotence. In experiments with bufo, it was found that it actually produces a number of disgusting symptoms. Causes a kind of dementia, and the person loses all modesty.
Modern research has confirmed the correctness of the described symptoms. Indole derivatives, bufotenin and bufotenidine, have been isolated from toad venom. The appointment of bufotenin in large doses leads to the development of psychosis, similar in clinical picture to those that occur after the well-known hallucinogen - lysergic acid diethylamide (LSD). In small doses, bufotenin has a tonic effect. After the introduction of 1-2 mg of bufotenin to healthy people, there was a feeling of pressure in the chest, tingling of the face, and nausea. Doses of 4-8 mg caused a feeling of calm and visual hallucinations. After the introduction of even larger doses, symptoms of violation of time and space were added, the expression of thought was difficult, and errors in the calculation were observed. The disturbances described lasted for about an hour.
It should be noted that this substance was also found in the seeds of the South American plant Mimosacee piptadenja. The smelling powder from the seeds (or drink) was used by the warriors of the Indian tribes as a psychostimulant before the battle. Bufotenin is found in large quantities in the venom of Bufo alvaris.
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Bufotenin |
Another property of toad venom was discovered by G. A. Bulbuk in 1975, when the administration of stimulating doses of toxin to rats increased the average life span of animals after implantation of tumor cells. Complete resorption of tumors was observed in 18 - 20%.
All of the above gives the right to talk about the possibility of widespread introduction of the components of toad venoms into public health practice.
It should be noted that the poison of toads is used not only by people. For a long time, biologists have been struck by the strange behavior of hedgehogs. These animals have been observed to wet their needles with their saliva. This phenomenon was studied in detail by the American zoologist from the University of Adelphia Edmund Brodie. Hedgehogs are not common in the United States, the researcher acquired African animals. He discovered that when a hedgehog kills a toad, he first of all looks for glands in it that are behind the eyes, chews them, then “sprinkles” his spines with saliva with particles of the glands, and only after that he begins to eat the toad. “When I first saw it,” Brody recalled, “it seemed to me that the animal was dying. A stream of foam came out of the mouth, which, wriggling, diverged along the thorns. Interestingly, in the laboratory, the hedgehog began to salivate in response to even substrates such as tobacco, soap, or the smell of perfume. It was concluded that all substances that act on the nasopharyngeal region lead to a similar reaction. Numerous observations have led to the conclusion that the hedgehog seeks to increase the protective power of the spines. He uses someone else's poison to strengthen his own defenses. The fact that injections with "treated" needles are much more painful than injections with ordinary needles is confirmed by the experiments of Brody and his students.
A fairly large number of biologically active substances were found in frogs, the medicinal properties of which have been studied, however, much worse than in toads.
Frog meat is used in Chinese medicine to treat dysentery. In the II century. n. e. K. S. Samonik recommended for colds:
“If you boil a frog in oil, then, discarding the meat,
Let's warm up the limbs ... "
Since ancient times, there has been a belief: in order for milk not to turn sour, a frog must be placed in it. It was possible to establish that the mucus that wets the body of the frog has antimicrobial properties and prevents the development of lactic acid bacteria in milk.
In the American magazine Time, a report was published that scientist Michael Zasloff, working at the National Institute of Child Health and Human Development (USA), managed to isolate a peptide from the skin of an African toothed frog that can have a detrimental effect on a wide range of microorganisms.
At the Universities of Rostock and Greifswald (GDR), by irritating the skin of a clawed frog with electricity, mucus was obtained and its effect was tested on various bacteria and fungal spores. It turned out that it inhibits the growth of colonies of staphylococci and many other microorganisms. Heating the secret to 20° for 20 minutes did not affect its bactericidal properties, which indicates the stability of the active principle. The test substance had no noticeable effect on streptomycetes and fungal spores.
In the old days in Japan, there was a belief that sore eyes can be treated by applying frog muscle to them, and in Russian medical books, the healing properties of frog caviar were indicated.
Pai Sum in the book "Source of Health" gives the following recommendations: "Fresh frog roe wrapped in a rag is rubbed on the face several times a day to remove freckles. The frog skin collected in a bag is squeezed out and dried. If you burn part of the contents and the ashes, crushed into powder, taken orally (5 - 6 drachmas), it helps against kidney and uterine bleeding. If applied to a wound, it has a hemostatic effect. "For bloody urine, a plaster of frog roe, alum, lead sugar, and a small amount of camphor is applied to the pubis."
About the use of frog caviar by healers, V. Deriker can find the following lines: “In Poland, for rheumatism, frog caviar is applied to canvas, dried in the shade and applied to suffering places ...”. "In Estland, they rub their face with frog caviar to get rid of freckles." “Bloody urine in cows, caused by horsetail and wolfberry, is treated with an infusion of frog caviar. Infuse two glasses of caviar in one glass of alcohol and give 1/2 glass. V. Deriker also wrote that “from the sting of a snake to the wound, live frogs are applied with their belly to the wound. The frogs die one after another, at first quite quickly, then more slowly, until they are cured. Baron Iskul, in the Orel Provincial Gazette, reports that a snake stung a peasant woman on the foot, near the ankle; the whole leg up to the thigh was swollen, the patient complained of terrible pain not only in the leg, but also in the stomach; she was sweating profusely, feeling nauseous and unspeakably afraid. A passing peasant cured her in this way (Dr. Zdr., 1840, 287).”
The wound healing and bactericidal properties of frog caviar have now received scientific justification. In the shell of frog eggs, the substance ranidone was found, which kills microbes better than many well-known antiseptics.
Biologically active substances with different chemical structures were isolated from the skin of various frog species. The content of biogenic amines in them reaches 100 mg/g of skin (the most typical representative is serotonin and its N-methyl derivatives). The main groups of peptides are bradykinins, tachykinins and opioids. The first two cause vasodilation and a drop in blood pressure. Currently, the most studied peptides isolated from different types of frogs are physalanin, uperolein, cerulein, bombesin, and others.
The peptide cerulein was first isolated from the skin of the Australian white tree frog, and US Pat. No. 4,552,865 describes the preparation of a drug from the skin of this frog for the treatment of certain mental illnesses. In 1971, the Australian zoologist R. Endin published a report in the journal Science et Avenir, who isolated cerulein from the skin of a small green tree frog common in Australia. This substance reduced pressure, contracted the gallbladder, stimulated the secretion of gastric juice.
Bombesin peptide was isolated from the skin of toads, which has a pronounced effect on bile secretion and gastric secretion. Interestingly, bombesin is found in the mammalian brain, where it acts as a regulator of the functional activity of the stomach. In 1979, in the journal Chemical and Engineering News (No. 47), a report was published that bombesin, isolated from the skin of frogs, has the ability to reduce appetite, for example, in rats.
Of particular interest are opioid peptides - dermorphins, isolated from the skin of one of the frog species and having analgesic activity, 11 times higher than morphine. Dermorphs exceed the biological effect of endogenous human and animal opiate-like peptides - leu- and met-enkephalin.
It is known that all proteins and peptides of the world around us consist of amino acids, which are represented by levorotatory isomers. A unique feature of permorphine is the presence of a dextrorotatory isomer of the amino acid alanine in its polypeptide chain. This phenomenon is very rare in nature. Replacement of a dextrorotatory isomer with a levorotatory one leads to a loss of activity.
Spiropiperidine alkaloid, hystrionicotoxin, was isolated from the skin of one of the species of the Colombian frog, which acts on neuromuscular transmission in skeletal muscles, blocking the action of acetylcholine on muscle H-cholinergic receptors, and also blocking the ion channel of the subsynaptic membrane, allosterically associated with these receptors. Another alkaloid, gefirotoxin, blocks M-cholinergic receptors of smooth muscles, and pumiliotoxins A, B, and C alkaloids facilitate the passage of calcium ions through cell membranes and enhance the coupling of excitation processes with muscle contraction and the secretion of mediators. They cause the development of convulsions of the skeletal and respiratory muscles and death.
From the skin of Panamanian frogs, the substance cetecitoxin, which has the ability to lower blood pressure, has been isolated. This effect is not associated with an effect on the nerve ganglia.
The described compounds are not used in medicine, and the possibility of their introduction into the practice of treatment is currently being investigated.
Speaking about the medicinal properties of biologically active substances isolated from the skin of toads and frogs, it is impossible not to talk about the Colombian coca frog, from the skin of which the most powerful of the currently known non-protein poisons, batrachotoxin, has been isolated. Back in 1860, the Spanish doctor Posado Arancho, while visiting Colombian Indians, observed how hunters were preparing poisoned arrows with the poison of coca frogs. The technique has survived to this day, as the American traveler Martha Latham wrote about. The poison of coca frogs is used by the Choco Indians to poison arrows. It is almost impossible to find animals in impenetrable thickets. Therefore, the Indians make sounds that imitate the voice of a frog. Hearing an answering whistle, they go to the place where the frog is hiding. Protecting their hand with leaves, hunters collect frogs and carry them to the village. Coca poison does not work through the skin, but with the slightest scratch, the poison can enter the bloodstream and cause poisoning. Having strung a live frog on a thin bamboo stick, the Indians hold it over the flame of a fire. Under the influence of high temperature, a poisonous milky liquid is released on the skin. The ends of the arrows are moistened with this liquid and dried in the shade; The poison from one frog is enough to poison about fifty arrows. In addition, to keep the poison better, the Indians make notches on their arrows. An animal wounded by such an arrow becomes paralyzed and dies. After cutting a piece of meat with an arrow and throwing it away, the animals are then eaten.
The American chemist and biochemist B. Witkop managed to reveal the structure of coca poison. Martha Latham, in her memoirs of an expedition to the jungles of Colombia, cites the words of Dr. Witkop, told to her: “It is possible that a good medicinal preparation can be obtained from coca poison. Similar poisons are already being used as cardiac stimulants. Nothing can be known in advance. In any case, this is a very interesting substance, it deserves serious attention.
Difficulties in studying it arose primarily due to the fact that frogs are very small. An adult animal a little over one gram reaches a length of 2 - 3 cm and can fit in a teaspoon. From 100 frogs, 275 mg of crude extract can be obtained and then about 1 mg of purified poison can be isolated. M. Latham managed to collect thousands of coca frogs. However, when they were sent to Washington, they died, and the poison collapsed in the skin of a dead frog. Then M. Latham developed a method of extracting the poison on the spot, and the finished extract was sent to the laboratory of B. Witkop for research. To finally solve the problem of raw materials, a special terrarium was built in Witkop's laboratory for breeding coca. The difficulty was also that the poison turned out to be an unstable compound and quickly collapsed during storage. It was possible to isolate four main components of the active principle of the poison: batrachotoxin, homobatrachotoxin, pseudobatrachotoxin and batrachotoxin A. The most stable compound is batrachotoxin A. It was obtained in crystalline form, studied using modern physical methods. Its structure was deciphered. Then the structure of batrachotoxin was established. This poison has a steroidal structure with several substituents and is an ester of batrachotoxin A with 2,4-dimethylpyrrole-3-carboxylic acid; Batrachotoxin is a derivative of the steroid pregnin.
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Batrachotoxin |
At present, it has been possible to synthesize batrachotoxin and create its analogue, twice the toxicity of natural poison. A pharmacological study showed that the mechanism of action of the poison is similar to that of curare. Different sensitivity of animals to this poison was found. Rabbits and dogs are 100 times more sensitive to it than mice. Lethal doses for frogs and toads are thousands of times higher than for mice.
Batrachotoxin is the most toxic poison among amphibian steroidal alkaloids. Dose causing
The 50% mortality in mice (LD50), expressed in µg/kg, is: batrachotoxin - 2, homobatrachotoxin - 3, samandarin - 300, batrachotoxin A - 1000, pumiliotoxin A - 1500, pumiliotoxin B - 2500. These data are given in book "Zootoxinology" by B. N. Orlov and D. B. Gelashvili (1985).
To compare the toxicity of batrachotoxin with known poisons, we provide a table from which it can be seen that it is the most powerful non-protein poison. The high toxicity of the poison makes it difficult to use it for medicinal purposes. An effective antidote has not yet been found, except for tetrodotoxin (poison from puffer fish), which is an antagonist of batrachotoxin and is also highly toxic.
The pharmacological properties of biologically active substances in other amphibians have been studied much worse than in toads and frogs.
Of the caudate amphibians, salamander skin secretion may be of interest for medical practice, which contains a number of alkaloid-like substances: samandarin, samandaron, O-acetylsamandarin, samandaridine, etc. They have pronounced antimicrobial activity. From frogtooths - tailed amphibians that live in the rivers of the Dzungarian Ala-Tau in Kazakhstan - Chinese healers prepared a remedy for restoring youth and sold it for a lot of money.
It should be noted that the most expensive Vietnamese medicine of animal origin is the gecko lizard, preparations from which have a tonic and aphrodisiac effect and are used in the treatment of tuberculosis and asthma.
It is impossible not to say what a huge role frogs played in the knowledge of wildlife and its laws. If we evaluate the quantitative participation of animals in various scientific experiments, then one of the first places will belong to them. “... I will flatten the frog and see what is happening inside it; and since you and I are the same frogs, we only walk on our feet, I will know what is happening inside us, ”said Bazarov, the hero of Turgenev’s work Fathers and Sons.
For many centuries, frogs have served and now serve zoologists, anatomists, physiologists, doctors and pharmacologists. More recently (before the development of methods for radioimmunological determination of chorionic gonadotropin in the urine, an increase in the content of which is a sign of pregnancy), male frogs were used to diagnose pregnancy. A timely reaction to these animals saved more than one woman with an ectopic pregnancy. At one time, the frog served as an invaluable service to the Italian scientists Luigi Galvani and Alexander Volta in conducting experiments that led to the discovery of galvanic current and "magnetic electricity". Galvani's experiments on frogs marked the beginning of an important science - electrophysiology.
A large number of experiments on frogs were carried out by the Russian physiologist I. M. Sechenov. The results of the research were summarized by him in the famous monograph "Reflexes of the Brain". This book dealt a blow to idealism, and a lawsuit was initiated against Sechenov. “Why do I need a lawyer? I will take a frog with me to court and do all my experiments in front of the judges: then let the prosecutor refute me? Such was the answer of the scientist to the accusations of obscurantists.
When the number of frogs that died in the experiments reached 100,000, medical students in the city of Tokyo erected a monument to the frog. The same monument to the inglorious assistant was opened at the end of the 19th century. at the Sorbonne-University of Paris.
3
Neptune's Pharmacy .................................................. .........................................6
Medicinal amphibians .................................................................. ......................... 31
Healing Snake .............................................................. ................................. 46
Pharmaceutical Insects .................................................................. ........................... 55
Weapons of spiders and scorpions ............................................... ................... 82
The worm helps the patient ............................................... ....................... 91
Odorous molecules of animals .............................................. ................... 98
Medicines from the horn ............................................... ............................................... 108
Healing properties of waste products ............................................... 117
Healing organs .................................................................. ...................................... 134
Paradoxes of the animal world .............................................................. ...................... 168
Literature ................................................. ................................................. 184
It is currently established that among amphibians, toads can be attributed to medicinal animals. Wet warty skin, large mouth, bulging eyes have always evoked superstitious fear and disgust for these animals among the people. Since ancient times, they have been companions of witches and sorcerers and have served as a means of magic healers. The most studied representative of these ugly warty animals was named by C. Linnaeus Bufo bufo L.
Three types of toads live in the European part of the USSR: terrestrial, reed and gray (common). The latter is the most common and is larger than the green and reed.
It has long been observed that the skin secretion of toads is a poison to animals. Since the introduction of toads from South America to protect crops from pests in Australia, dingoes have often been observed dying after eating them. The same thing happened with Australian snakes. Academician P.S. Pallas wrote that his “hunting dog, after biting a toad, became seriously ill and died. Before that, after hunting for toads, she had swollen lips. In dogs that do not hunt, the smell of the skin of toads is disgusting. So, for example, A. Bram wrote: “One has only to hold a toad in front of the nose of well-bred dogs, as one wrinkles its nose and forehead skin and turns its head away, the other tucks its tail and nothing can force it to come closer again.”
There are descriptions of poisoning with toad venom in humans. The famous French physician Ambroise Pare wrote in 1575: “Not far from Toulouse, two merchants, while walking in the garden, picked sage leaves and put them in wine. After drinking the wine, they soon felt dizzy and fainted; vomiting and cold sweat appeared, the pulse disappeared, and death quickly occurred. The judicial investigation established that in the place of the garden where the sage grew, there were a lot of toads; hence it was concluded that the poisoning followed from the poison of the toads that fell on the indicated plant. There have been cases of poisoning of people in Argentina when they put the skin of a toad behind their cheeks to treat a toothache. After the pain subsided, the patient fell asleep, and by morning he was dead.
For medicinal purposes toad poison has been used for a long time. Powder obtained from toad skins in the form of smooth round dark brown scales was used in China under the name "Chang-Su", and in Japan - "Sen-Co". Inside it was used for dropsy, to improve cardiac activity, and externally in the form of cakes as a remedy for toothache, inflammation of the paranasal sinuses and bleeding gums.
In the Hutsulshchyna, in order to get rid of the “pasnitsa” (it is not known what disease was meant by this name), the green toad was insisted in water, and it was recommended to drink the infusion in small portions. In Boykovshchina, they rubbed their feet with a toad, believing that they would never get sick.
For therapeutic purposes, not only toad poison is used, but also meat. At the Institute of Oriental Medicine of the Socialist Republic of Vietnam, it is prescribed to children with dystrophy in the form of Com Cae tablets, which also include yolk and dried banana. Chinese doctors recommend using toad meat in the treatment of bronchial asthma and as a tonic.
At present, a preparation from the poison of Chinese toads called "mapin" (according to the Japanese pharmacopoeia of 1951) is used for therapeutic purposes in many countries of the East. In 1965, Japanese scientists Iwatsuki, Yusa, and Kataoka reported the successful clinical use of components isolated from toad venom.
S. V. Pigulevsky cites the information of researchers Growth and Paul, according to which toad venom was widely used in the treatment of dropsy before the introduction of foxglove. It was also used to poison arrows. One of the first researchers of the nature of toad venom, the famous French physiologist Claude Bernard wrote over 400 years ago that "the poison resists the action of heat, it is soluble in alcohol and that, in a word, it is as resistant as the poison of arrows." “Here, for example, are the arrows given to me by Mr. Busengo - they are from South America. I don't know at all what the nature of the poison they contain is. It is not curare, as was supposed, because its toxic effect is on the muscles, not on the nerves. I am inclined to think that it is the poison of the toads, which abounds in the country where these arrows are made; the venom of toads is indeed a very energetic effect on the muscle fiber.
Subsequent researchers found that the natives of South America extract the poison of the skin glands of toads by boiling, adding poisonous plants to the boiling solution to enhance its toxic effect.
The mass of dried poison from one toad is 16 mg in males and 27 mg in females. In the form of white foam, it flows freely from the skin glands to the surface of the body. From the parotid glands (parotid), it can be sprayed with force at a distance of up to a meter. According to V. I. Zakharov, toad venom in dilutions of 1: 100 and 1: 1000 after 20 minutes causes paralysis of the limbs and death of ticks. Toad venom, injected into the blood of small birds and lizards, kills them in a few minutes. Rabbits, guinea pigs and dogs die in less than an hour.
In 1935, the Soviet researcher F. Talyzin caught 16 green toads in Kyrgyzstan, removed their skin, dried it and stored it until 1965, after which he studied its toxic properties. It was found that after 30 years of storage in relatively unfavorable conditions of humidity and temperature, toad venom almost does not lose its characteristic toxic properties.
Currently, the most studied compound isolated from toad venom is bufotoxin, an ester of the steroid bufogenin with the dipeptide suberylarginine,
Like many other animal poisons, toad toxin contains phospholipase A.
In 1978, B. N. Orlov and V. N. Krylov compiled a table in which the physiologically active substances of toad venom are represented by two groups of chemical compounds (see p. 35).
Toad venom contains up to 5 - 7% of adrenaline. It should be noted that in the human adrenal glands, its concentration is four times less. The high content of this compound, which has a vasoconstrictive effect, can explain the use of the Chinese drug "Chang-Su" as an external hemostatic agent.
It should be noted that the composition of the venom of different species of toads has certain quantitative fluctuations, and the isolated bufotoxins differ, as a rule, in the radicals of the steroid part of the molecules.
Like other steroids, toad venom is synthesized in the body from cholesterol.
In official medicine, messages about its medicinal properties appeared at the end of the last century, when a woman addressed the Italian doctor S. Staderini with complaints of pain in her eye. She said that she grabbed a toad with her fireplace tongs, which got into the room. At that moment, the toad violently sprayed poison from the parotid glands, a drop of which fell into the eye. At first, the woman felt pain, then there was a loss of sensitivity. This case forced Staderini to conduct animal studies and study the analgesic properties of toad venom. A 1% solution, unlike a concentrated solution, did not cause severe eye irritation, while at the same time providing long-term anesthesia. After animal studies, he applied the new anesthetic to humans and published his observations in 1888. According to Staderini, an aqueous solution of toad venom is capable of displacing cocaine from practice, which at that time was often used for local anesthesia, in terms of the effectiveness of anesthesia.
Cardiotropic action of toad venom was studied by N. P. Kravkov, F. F. Talyzin, V. I. Zakharov and the Japanese scientist Okada. The effect of various doses of the poison of common toads on the heart of warm-blooded animals was studied in 1974 by B. N. Orlov and V. N. Krylov. These authors found that toad venom had a pronounced stimulating effect on the isolated heart of a cat. At the same time, the effect was manifested in a wide range of dilutions - from 1: 5000 to 1: 1000000 g/ml. The same stimulating effect was observed when the poison was introduced into the body - there was an increase in the strength and frequency of heart contractions, an increase in pulse pressure, a decrease in the systological index, etc. Probably, the effect of the poison is associated with the stimulation of tissue metabolism in the heart muscle, since this effect was also observed on isolated heart and blockade of nerve endings with chemicals. In addition, the poison, apparently, has a direct effect on the conduction system of the heart and the nodes of automatism. This can be judged, but the fact that the administration of poison in large doses caused atrioventricular blockade and the appearance of a ventricular rhythm, arrhythmias were observed. This scientifically confirmed the use of toad venom in folk medicine for heart failure. After the systematic introduction of toad venom, an increase in blood pressure is observed due to an increase in heart contractions, as well as a decrease in the rhythm of cardiac activity. Its action is close to the action of strophanthin "K".
It was also found that toad venom stimulates breathing, restores it even after a complete stop.
V. I. Zakharov used the poison of toads in the experimental therapy of radiation injuries. The introduction of toad venom to rats immediately after irradiation had a powerful stimulating effect on hematopoiesis, accompanied by an increase in the production of leukocytes and platelets, as well as an increase in the phagocytic activity of leukocytes. An increase in animal survival was observed. The introduction of poison after irradiation also prevented the development of vascular damage and the occurrence of hemorrhages.
According to V.I. Zakharov, toad venom at a dilution of 1: 1000, 1: 2000 and 1: 4000 kills helminths of humans and animals in vitro: liver fluke within 30 minutes, pumpkin tapeworm - 37 - 48 minutes, unarmed tapeworm - 15 – 45 min. He also made experiments on the deworming of dogs and mares. After the application of the poison, a laxative effect was observed due to a sharp irritation of the intestines and a laxative was not prescribed. However, the author notes: "The emetic action of toad venom limits its use as an antihelminthic." It was also possible to establish that toad venom accelerates the healing process of wounds in experimental animals. There is a description of another property of toad venom, which is given by the American professor of homeopathy E. A. Farrington. In his lectures given at the Hahnemann Medical College in Philadelphia, he points out that one of the representatives of the toads of South America secretes on the surface of the body "an oily substance, considered poisonous. Local women, when they are too bothered by their husbands, mix this secretion into their drink to cause impotence. In experiments with bufo, it was found that it actually produces a number of disgusting symptoms. Causes a kind of dementia, and the person loses all modesty.
Modern research has confirmed the correctness of the described symptoms. Indole derivatives, bufotenin and bufotenidine, have been isolated from toad venom. The appointment of bufotenin in large doses leads to the development of psychosis, similar in clinical picture to those that occur after the well-known hallucinogen - lysergic acid diethylamide (LSD). In small doses, bufotenin has a tonic effect. After the introduction of 1-2 mg of bufotenin to healthy people, there was a feeling of pressure in the chest, tingling of the face, and nausea. Doses of 4-8 mg caused a feeling of calm and visual hallucinations. After the introduction of even larger doses, symptoms of violation of time and space were added, the expression of thought was difficult, and errors in the calculation were observed. The disturbances described lasted for about an hour.
It should be noted that this substance was also found in the seeds of the South American plant Mimosacee piptadenja. The smelling powder from the seeds (or drink) was used by the warriors of the Indian tribes as a psychostimulant before the battle. Bufotenin is found in large quantities in the venom of Bufo alvaris.
Another property of toad venom was discovered by G. A. Bulbuk in 1975, when the administration of stimulating doses of toxin to rats increased the average life span of animals after implantation of tumor cells. Complete resorption of tumors was observed in 18 - 20%.
All of the above gives the right to talk about the possibility of widespread introduction of the components of toad venoms into public health practice.
It should be noted that the poison of toads is used not only by people. For a long time, biologists have been struck by the strange behavior of hedgehogs. These animals have been observed to wet their needles with their saliva. This phenomenon was studied in detail by the American zoologist from the University of Adelphia Edmund Brodie. Hedgehogs are not common in the United States, the researcher acquired African animals. He discovered that when a hedgehog kills a toad, he first of all looks for glands in it that are behind the eyes, chews them, then “sprinkles” his spines with saliva with particles of the glands, and only after that he begins to eat the toad. “When I first saw it,” Brody recalled, “it seemed to me that the animal was dying. A stream of foam came out of the mouth, which, wriggling, diverged along the thorns. Interestingly, in the laboratory, the hedgehog began to salivate in response to even substrates such as tobacco, soap, or the smell of perfume. It was concluded that all substances that act on the nasopharyngeal region lead to a similar reaction. Numerous observations have led to the conclusion that the hedgehog seeks to increase the protective power of the spines. He uses someone else's poison to strengthen his own defenses. The fact that injections with "treated" needles are much more painful than injections with ordinary needles is confirmed by the experiments of Brody and his students.
A fairly large number of biologically active substances were found in frogs, the medicinal properties of which have been studied, however, much worse than in toads.
Frog meat is used in Chinese medicine to treat dysentery. In the II century. n. e. K. S. Samonik recommended for colds:
“If you boil a frog in oil, then, discarding the meat,
Let's warm up the limbs ... "
Since ancient times, there has been a belief: in order for milk not to turn sour, a frog must be placed in it. It was possible to establish that the mucus that wets the body of the frog has antimicrobial properties and prevents the development of lactic acid bacteria in milk.
In the American magazine Time, a report was published that scientist Michael Zasloff, working at the National Institute of Child Health and Human Development (USA), managed to isolate a peptide from the skin of an African toothed frog that can have a detrimental effect on a wide range of microorganisms.
At the Universities of Rostock and Greifswald (GDR), by irritating the skin of a clawed frog with electricity, mucus was obtained and its effect was tested on various bacteria and fungal spores. It turned out that it inhibits the growth of colonies of staphylococci and many other microorganisms. Heating the secret to 20° for 20 minutes did not affect its bactericidal properties, which indicates the stability of the active principle. The test substance had no noticeable effect on streptomycetes and fungal spores.
In the old days in Japan there was a belief that sore eyes can be treated by applying frog muscle to them, and in Russian medical books, the healing properties of frog caviar were indicated.
Pai Sum in the book "Source of Health" gives the following recommendations: "Fresh frog roe wrapped in a rag is rubbed on the face several times a day to remove freckles. The frog skin collected in a bag is squeezed out and dried. If you burn part of the contents and the ashes, crushed into powder, taken orally (5 - 6 drachmas), it helps against kidney and uterine bleeding. If applied to a wound, it has a hemostatic effect. "For bloody urine, a plaster of frog roe, alum, lead sugar and a small amount of camphor is applied to the pubis."
About the use of frog caviar by healers, V. Deriker can find the following lines: “In Poland, for rheumatism, frog caviar is applied to canvas, dried in the shade and applied to suffering places ...”. "In Estland, they rub their face with frog caviar to get rid of freckles." “Bloody urine in cows, caused by horsetail and wolfberry, is treated with an infusion of frog caviar. Infuse two glasses of caviar in one glass of alcohol and give 1/2 glass. V. Deriker also wrote that “from the sting of a snake to the wound, live frogs are applied with their belly to the wound. The frogs die one after another, at first quite quickly, then more slowly, until they are cured. Baron Iskul, in the Oryol Provincial Gazette, reports that a snake stung a peasant woman on the foot, near the ankle; the whole leg up to the thigh was swollen, the patient complained of terrible pain not only in the leg, but also in the stomach; she was sweating profusely, feeling nauseous and unspeakably afraid. A passing peasant cured her in this way (Dr. Zdr., 1840, 287).”
The wound healing and bactericidal properties of frog caviar have now received scientific justification. In the shell of frog eggs, the substance ranidone was found, which kills microbes better than many well-known antiseptics.
Biologically active substances with different chemical structures were isolated from the skin of various frog species. The content of biogenic amines in them reaches 100 mg/g of skin (the most typical representative is serotonin and its N-methyl derivatives). The main groups of peptides are bradykinins, tachykinins and opioids. The first two cause vasodilation and a drop in blood pressure. Currently, the most studied peptides isolated from different types of frogs are physalanin, uperolein, cerulein, bombesin, and others.
The peptide cerulein was first isolated from the skin of the Australian white tree frog, and US Pat. No. 4,552,865 describes the preparation of a drug from the skin of this frog for the treatment of certain mental illnesses. In 1971, the Australian zoologist R. Endin published a report in the journal Science et Avenir, who isolated cerulein from the skin of a small green tree frog common in Australia. This substance reduced pressure, contracted the gallbladder, stimulated the secretion of gastric juice.
The bombesin peptide, which has a pronounced effect on bile secretion and gastric secretion, was isolated from the skin of toads. Interestingly, bombesin is found in the mammalian brain, where it acts as a regulator of the functional activity of the stomach. In 1979, in the journal Chemical and Engineering News (No. 47), a report was published that bombesin, isolated from the skin of frogs, has the ability to reduce appetite, for example, in rats.
It is known that all proteins and peptides of the world around us consist of amino acids, which are represented by levorotatory isomers. A unique feature of permorphine is the presence of a dextrorotatory isomer of the amino acid alanine in its polypeptide chain. This phenomenon is very rare in nature. Replacement of a dextrorotatory isomer with a levorotatory one leads to a loss of activity.
Spiropiperidine alkaloid, histrionicotoxin, was isolated from the skin of one of the species of the Colombian frog, which acts on neuromuscular transmission in skeletal muscles, blocking the action of acetylcholine on muscle H-cholinergic receptors, and also blocking the ion channel of the subsynaptic membrane, allosterically associated with these receptors. Another alkaloid, gefirotoxin, blocks M-cholinergic receptors of smooth muscles, and pumiliotoxins A, B, and C alkaloids facilitate the passage of calcium ions through cell membranes and enhance the coupling of excitation processes with muscle contraction and the secretion of mediators. They cause the development of convulsions of the skeletal and respiratory muscles and death.
From the skin of Panamanian frogs, the substance cetecitoxin, which has the ability to lower blood pressure, has been isolated. This effect is not associated with an effect on the nerve ganglia.
The described compounds are not used in medicine, and the possibility of their introduction into the practice of treatment is currently being investigated.
Speaking of medicinal properties of biologically active substances isolated from the skin of toads and frogs, It is impossible not to talk about the Colombian coca frog, from the skin of which the most powerful of the currently known non-protein poisons, batrachotoxin, has been isolated. Back in 1860, the Spanish doctor Posado Arancho, while visiting Colombian Indians, observed how hunters were preparing poisoned arrows with the poison of coca frogs. The technique has survived to this day, as the American traveler Martha Latham wrote about.
The poison of coca frogs is used by the Choco Indians to poison arrows. It is almost impossible to find animals in impenetrable thickets. Therefore, the Indians make sounds that imitate the voice of a frog. Hearing an answering whistle, they go to the place where the frog is hiding. Protecting their hand with leaves, hunters collect frogs and carry them to the village. Coca poison does not work through the skin, but with the slightest scratch, the poison can enter the bloodstream and cause poisoning. Having strung a live frog on a thin bamboo stick, the Indians hold it over the flame of a fire. Under the influence of high temperature, a poisonous milky liquid is released on the skin. The ends of the arrows are moistened with this liquid and dried in the shade; The poison from one frog is enough to poison about fifty arrows. In addition, to keep the poison better, the Indians make notches on their arrows. An animal wounded by such an arrow becomes paralyzed and dies. After cutting a piece of meat with an arrow and throwing it away, the animals are then eaten.
The American chemist and biochemist B. Witkop managed to reveal the structure of coca poison. Martha Latham, in her memoirs of an expedition to the jungles of Colombia, cites the words of Dr. Witkop, told to her: “It is possible that a good medicinal preparation can be obtained from coca poison. Similar poisons are already being used as cardiac stimulants. Nothing can be known in advance. In any case, this is a very interesting substance, it deserves serious attention.
Difficulties in studying it arose primarily due to the fact that frogs are very small. An adult animal a little over one gram reaches a length of 2 - 3 cm and can fit in a teaspoon. From 100 frogs, 275 mg of crude extract can be obtained and then about 1 mg of purified poison can be isolated. M. Latham managed to collect thousands of coca frogs. However, when they were sent to Washington, they died, and the poison collapsed in the skin of a dead frog. Then M. Latham developed a method of extracting the poison on the spot, and the finished extract was sent to the laboratory of B. Witkop for research. To finally solve the problem of raw materials, a special terrarium was built in Witkop's laboratory for breeding coca. The difficulty was also that the poison turned out to be an unstable compound and quickly collapsed during storage. It was possible to isolate four main components of the active principle of the poison: batrachotoxin, homobatrachotoxin, pseudobatrachotoxin and batrachotoxin A. The most stable compound is batrachotoxin A. It was obtained in crystalline form, studied using modern physical methods. Its structure was deciphered. Then the structure of batrachotoxin was established. This poison has a steroidal structure with several substituents and is an ester of batrachotoxin A with 2,4-dimethylpyrrole-3-carboxylic acid; Batrachotoxin is a derivative of the steroid pregnin.
At present, it has been possible to synthesize batrachotoxin and create its analogue, twice the toxicity of natural poison. A pharmacological study showed that the mechanism of action of the poison is similar to that of curare. Different sensitivity of animals to this poison was found. Rabbits and dogs are 100 times more sensitive to it than mice. Lethal doses for frogs and toads are thousands of times higher than for mice.
Batrachotoxin is the most toxic poison among amphibian steroidal alkaloids. The dose that causes 50% mortality in mice (LD50), expressed in μg / kg, is: batrachotoxin - 2, homobatrachotoxin - 3, samandarin - 300, batrachotoxin A - 1000, pumiliotoxin A - 1500, pumiliotoxin B - 2500. These information is given in the book "Zootoxinology" by B. N. Orlov and D. B. Gelashvili (1985).
To compare the toxicity of batrachotoxin with known poisons, we provide a table from which it can be seen that it is the most powerful non-protein poison.
With prolonged administration, batrachotoxin has a strong cardiotoxic effect, accompanied by a violation of the rhythm of cardiac activity, myocardial fibrillation and death. The poison has a strong neurotropic effect. It has the property of causing depolarization of the muscle membrane by increasing its permeability to sodium ions. With the help of batrachotoxin, the function of sodium channels, excitable cell membranes, is currently being studied.
In nature, batrachotoxin was found in four more species of frogs (except coca) of the genus Phyllobates living in South America.
The high toxicity of the poison makes it difficult to use it for medicinal purposes. An effective antidote has not yet been found, except for tetrodotoxin (poison from puffer fish), which is an antagonist of batrachotoxin and is also highly toxic.
The pharmacological properties of biologically active substances in other amphibians have been studied much worse than in toads and frogs.
Of the caudate amphibians, salamander skin secretion may be of interest for medical practice, which contains a number of alkaloid-like substances: samandarin, samandaron, O-acetylsamandarin, samandaridine, etc. They have pronounced antimicrobial activity. From frogtooths - tailed amphibians that live in the rivers of the Dzungarian Ala-Tau in Kazakhstan - Chinese healers prepared a remedy for restoring youth and sold it for a lot of money.
It should be noted that the most expensive Vietnamese medicine of animal origin is the gecko lizard, preparations from which have a tonic and aphrodisiac effect and are used in the treatment of tuberculosis and asthma.
It is impossible not to say what a huge role frogs played in the knowledge of wildlife and its laws. If we evaluate the quantitative participation of animals in various scientific experiments, then one of the first places will belong to them. “... I will flatten the frog and see what is happening inside it; and since you and I are the same frogs, we only walk on our feet, I will know what is going on inside us, ”said Bazarov, the hero of Turgenev’s work Fathers and Sons.
For many centuries, frogs have served and now serve zoologists, anatomists, physiologists, doctors and pharmacologists. More recently (before the development of methods for radioimmunological determination of chorionic gonadotropin in the urine, an increase in the content of which is a sign of pregnancy), male frogs were used to diagnose pregnancy. A timely reaction to these animals saved more than one woman with an ectopic pregnancy. At one time, the frog served as an invaluable service to the Italian scientists Luigi Galvani and Alexander Volta in conducting experiments that led to the discovery of galvanic current and "magnetic electricity". Galvani's experiments on frogs marked the beginning of an important science - electrophysiology.
A large number of experiments on frogs were carried out by the Russian physiologist I. M. Sechenov. The results of the research were summarized by him in the famous monograph "Reflexes of the Brain". This book dealt a blow to idealism, and a lawsuit was initiated against Sechenov. “Why do I need a lawyer? I will take a frog with me to court and do all my experiments in front of the judges: then let the prosecutor refute me? Such was the answer of the scientist to the accusations of obscurantists.
When the number of frogs that died in the experiments reached 100,000, medical students in the city of Tokyo erected a monument to the frog. The same monument to the inglorious assistant was opened at the end of the 19th century. at the Sorbonne-University of Paris.
