Useful poison

Useful poison. TOXINS ACT ON THE NERVESRussian chemists will study the most unusual and poorly studied poisons. Why they need it and the benefit to mankind from the study of poisons?

Purple pusiste looks smooth, like droplets of liquid metal eyes. From the ground, covering the bottom of the terrarium, except for the eyes, stick dark hairy legs. Actually, this spider from the genus of Poecilotheria usually lives in the trees of Sri Lanka. It builds aerial nests in trees, and if a careless lover of bananas or coconuts will disturb his rest, the spider quickly swoops at the man, bites the skin and injects a few milligrams of venom. Man is still alive, but suffering agonizing cramps and long, sometimes for many weeks.

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— Currently, the spiders, the venom of which is a deadly danger to humans are relatively well understood, — says Antonina eagle, employee group, molecular tools for neuroscience, Institute of Bioorganic chemistry (IBCH). M. M. Shemyakin and Y. A. Ovchinnikov Russian Academy of Sciences. — We are interested in unusual poisons like the one that distinguish these spiders. It is interesting to study its composition and to understand which so long manifested toxicity.

It is on the study of unusual properties of the venoms and poisons of animals little studied received a grant from the RSF scientists from the Institute of Bioorganic chemistry under the direction of biochemist Alexander Vasilevsky. Centipedes, jellyfish, sea urchins, rays and leaf-beetles in various circumstances which rarely attracted the attention of scientists: someone who seemed not very dangerous, while others dwelt where long gone before the Europeans, and third at all for a long time considered non-toxic. The scientists will be to understand what substances respond to unknown poisons for toxicity, and determine the molecular mechanism of their action. In the future, with this knowledge, you will not only create the antidote, but also to develop, on the basis of the toxins of the drugs.

We thought that if in the known poisons discovered a lot of interesting from the point of view of application of substances, it is possible that we will find something like this from little-studied animals, — says Alexander Vasilevsky. — The selection we were guided by several criteria. Besides the fact that it has to be little studied, the animal should be available, that is dwell in the territory of Russia or to sell to kennels or pet stores. Well, there must be an indication of some unusual effects of toxins.

So much can kill a Brazilian wandering spider one portion of its poison.

Poisons animals for scientists who love to solve mysteries of nature, is a real Klondike. The phenomenon of toxicity — the most ancient form of defense and chemical communication — have generated a number of toxins and ways to protect them, to understand them for decades. For example, it is interesting to know why the solenodon is a mammal feisty character, is not immune to their own poison and die from minor scratches that are sometimes applied themselves during a fight? Or how is it that some species, for example, conventional pig, quietly takes the bite of a rattlesnake? Why are poisons spiders contain thousands of components, and the poison of a bee — just the two?

— It is known that in the southern part of Africa inhabited by bugs ciampedie, — said Petr Oparin, too, working in the group of molecular tools for neuroscience. Aboriginal produced from them toxic. It is, in all probability, one of the most poisonous natural toxins, as a poisoned arrow strikes adult elephants and giraffes. But what this substance is and how it works, nobody knows. As in Russia these beetles no one does, we decided to study their relatives — Colorado beetles. Their hemolymph also has a toxic effect on animals is selective.

Milk Paukov lab, where they study poisons, dangerous creatures, try not to hold. The only animal that lives here permanently — African clawed frog, whitish creature, like a large boiled dumpling c legs. It is not toxic at all, but with its help it is convenient to evaluate the toxicity of the poisons.

Scary hairy spiders with a leg span of 15 centimeters living in the Moscow zoo under the supervision of arachnology Daniil Osipov, from the biochemists, as a rule, receive a vial of poison. On the table is a vial with a transparent slightly viscous liquid is poison one of the most dangerous tarantulas. He lives in Africa and inspired there panic the locals for its aggressiveness and rapidity of movement. Scientists suggest that it is because of him humanity has developed arachnophobia. To extract the poison of this monster is a special art. Let's start with the fact that spider being milked. "Milking machine" is a special box for the insect, carbon dioxide, and two electrodes.

Milking a spider isn't a new technology, it was developed in the 50's. it's another thing to milk a sea urchin.

— Spider euthanized with carbon dioxide, then it is electrocuted, and it secretes poison. If the spider had not milked, milk yield may reach 4 milligrams of venom. The average milking the insect is two to three times a week, — says Antonina eagle. — Exercise is dangerous, so do wears rubber gloves and even sleeping spider holds a long tweezers — just in case.

With all of the exoticism of the process of milking a spider isn't a new technology. Various techniques began to make since as chemists in the 1950s, and seriously began studying the venom of spiders to search for antidotes. Their traditions of production of poison has developed in the Brazilian Butantan, the oldest Institute for the study of venoms and domestic scientists, for example, in the Department of molecular neurobiology the Institute of Bioorganic chemistry, headed by academician E. V. Grishin.

It's another thing to milk a sea urchin. Such a need, even in the scientific world people face often. For hedgehogs biochemists go to the pet store. However, usually fans of aquarium buying them one by one and to work in the lab requires a large number of echinoderms, so you have to call in advance and ask them to gather in the name of science big party.

25%Is the probability that a Viper bite will not lead to the development of intoxication and deterioration of General condition.

The difficulty is that the urchins venom not so much — explains the officer Group, molecular tools for neuroscience Maria Sachkov. — To get a few grams — a teaspoon — of liquid, you need to attract tens of hedgehogs.

A generally accepted method of taking away the poison doesn't exist here, so this process is continuous creativity. We tried, for example, to apply electrical stimulation: it is important to choose the right voltage to angry hedgehog, but not to ruin. The second way to extract the poison — trimming-venomous pedicellaria (skeletal special education) on the animal's body and then to extract the desired substance. But Jerzy of course, not survive.

Part obtained by scientists of the poison immediately goes to work, the remainder sent to storage: frozen material retains its properties for months and in dried for decades. To dry the poison is placed in a special device that pulls moisture. The dried venom is a scattering of crystals — yellow or white as the driven snow.

— In our Department there is a "magic box", where the poisons are stored in 70 years — reveals the local secrets Antonina eagle. Mainly the poison of Scorpions and snakes were caught in Central Asia. Sometimes we refer to these powders in order to restore the poison, enough to add a certain amount of water.

On the nose Magic chest with rare poisons in the hall of the Institute of Bioorganic chemistry. It's a big fridge, a flashing figure of -70°C. it is packaged in glass jars and plastic boxes, are the poisons of Scorpions and snakes. They were collected when the study of bioazul has experienced a real boom. In the USSR, for example, constantly worked nine serpentarii that for the year collected 5-7 pounds of dry snake venom.

7 times.In so much poison sea snakes toxine poison the most venomous land snakes.

Having the opportunity to study matter at the molecular level, scientists have determined that the waste is a complex cocktail of dozens, and sometimes hundreds of thousands of different toxins. A significant part of them are neurotoxins, that is, substances acting on the nervous cells. Externally their effect is very similar: a person paralysis of muscles, and he's dying either from cardiac arrest or respiratory arrest. But despite the similarity of symptoms, the structure of the toxins and their mechanism of action was different. It is significant that the keen interest of biologists and chemists to neurotoxins allowed to make one of the most important discoveries of the twentieth century: to describe the molecular system, the nervous cells.

With the help of the neurotoxins of snakes and Scorpions, scientists have studied the structure, they affect sodium and calcium channels in the cell membranes, — says Alexander Vasilevsky. In the body they are responsible for conducting nerve impulses and muscle contraction. Toxins are attached to a certain type channels, block their work or, conversely, activates it and thereby imbalance in the cells.

Over time it became clear that the membranes of nerve cells like especially "stuffed" with a huge number of different types of receptors that can interact with a huge number of toxins. That is, the neurotoxins is a highly accurate molecular tool to influence the human nervous system. Knowing the structure of ion channels, it is possible to artificially create substances that can regulate the nerve cells, for example, to block the passage of nerve impulses.

Man enough to nanograms of botulinum toxin and he dies.

One of the interesting from this point of view, substances — latrotoxin, named in honor of Latrodectus spider (Latrodectus, or black widow). This is one of the few solenoidality arthropods inhabiting the territory of Russia, — it is found in sagebrush-covered steppes of Astrakhan, the black sea and sea of Azov. However, in hot years, some desperate individuals get to the suburbs. Particularly dangerous to humans, the venom of this small spider does exactly latrotoxin different from other toxins structure and action.

— Typically, the neurotoxins are small proteins, peptides that have their own target in the body of the victim — ion channels, — says biochemist Petr Oparin. — Latrotoxin, in contrast, the large protein, which, as it turned out, he forms a protein complex and of them "makes" their own channel, embedding in the cell membrane. How exactly this occurs is still unknown. As a result of the nerve endings EN masse to throw the neurotransmitters, which leads to a depletion of nerve endings and, as a result, total paralysis. We study exactly how to construct latrotoxin because it is unique exogenous extracellular ion channel that is stunningly complex transport system. Interestingly, in the venom of the black widow contains similar toxins are harmless to humans but deadly for insects. This effect can then be used to create a new kind of insecticides that affect insect pests. In the environment where the pests have learned to adapt to existing drugs, in this direction lay great hopes.

Nervous rabota.ochenj dealing with poisons all the time asking which of them is the strongest. And they all the time say different, because different organisms react to the same poison in different ways. Some call palytoxin, which is contained in the coral and is produced by virus-symbiota. It actively affects the coronary arteries and stops the heart. Others will remember the tetrodotoxin, which is stuffed inside a Japanese delicacy — puffer fish. Still from the venom of the fish of this family killed a few people a year that they do not have time to drive from the restaurant to the hospital. But still the most powerful toxins — bacterial. Their produce Clostridium botulinum bacteria — the tiny organisms that love to settle in my grandmother's mushrooms, and canned meat. To be poisoned to death, a person need to obtain several hundred thousand molecules of this substance, that's millionths of a gram.

However, in some cases, the worst toxin can cure. No wonder the original word "Pharmakon" in Greek means both medicine and poison.

For example, chlorotoxin is seen today as the agent for the treatment of cancer. It is contained in the venom of the Palestinian yellow Scorpion. From his injections in North Africa every year, killing dozens of people, mostly children. Nevertheless, it is chlorotoxin in small quantities interacts with cells of the glioma — brain tumors and blocks their mobility, that is, stops the development of metastases.

— It is significant that a close homologue of chlorotoxin first identified by scientists of the Institute of Bioorganic chemistry in the 70-ies, — says Maria Sachkov. But then, just determined that it is non-toxic to mammals. When we saw publications, showing anticancer activity of chlorotoxin, then decided to check in this direction our toxin and got similar results. We are now working with cell cultures and preparing materials for publication.

Interesting results are obtained and the work of biochemists with the venoms of other Scorpions. It turned out that the toxins can be used for the treatment of autoimmune diseases — multiple sclerosis, rheumatoid arthritis and type I diabetes.

— Although the cause of many of these diseases are still unknown, the mechanism of their development are similar in many ways — tells the employee group, molecular tools for neuroscience Alexei Kuzmenkov. For example, it is proved that for autoimmunity to respond to certain T-lymphocytes, and if you block in these cells potassium channels, the disease stops. This effect was shown in the early 2000's, and today several drugs are undergoing clinical trials. And the doctors are constantly looking for new formulas: as until now an effective therapy for some autoimmune diseases, pharmaceutical companies are investing in this area of huge funds.

Toxins triumphal burst into medicine, but I must admit, to specific pharmacological preparations on the basis of biotoxins yet comes infrequently. One of the clearest examples of such success — analgesic-based conotoxin isolated from the venom of the mollusk cone. It went on sale in 2004 and is considered stronger than morphine. Other painkillers toxins that are in preclinical testing or are already past their allocated staff IBCH.

— The main difficulties in developing such drugs is their toxicity and low efficiency, explains Alexander Vasilevsky. — When we estimate the effect of the substance on the isolated cell culture, all is going well, and when the substance enters the body, it is influenced by dozens of other factors that inhibit its action. As a result of the potential of thousands of compounds suitable is one.To find the "magic" molecule that requires months of work and the most modern equipment. Once scientists select a few promising from the point of view of the impact of substances, specifics of their toxicity test on the oocytes of clawed frogs — they are big, and they hardly have their own ion channels. If we are talking about a drug for humans, the oocyte pre-injected human mRNA that encodes interesting to scientists ion channels. If the toxin is effective, the researchers determined its structure and for further work to recreate his methods genetic engineering — gene cloned in bacteria. Otherwise, no spiders will not save enough.

The puffer fish. Most scientists are inclined to believe that the poison is tetrodotoxin is that it generates itself. His breed bacteria living in symbiosis with fish

How to get to the library?

On the one hand, to detect the desired toxin is like finding a needle in a haystack. On the other hand, are encouraged by the fact that needles can be a huge amount, and the haystack is truly a universal size.

— The amount of toxins almost indefinitely— says Wasilewski. — Imagine if in the venom of one spider of a thousand toxins, and the spiders 40 000 species, we get millions of substances. Before us is a huge library created by nature. We check the ambitious idea that in the nervous system, you can choose any receptor and to find him his "key". Interestingly, while she confirmed.

Highly dangerous and poisonous: the black widow and yellow Scorpion



P. S. And remember, only by changing their consumption — together we change the world! ©

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Source: kot.sh/statya/213/poleznaya-otrava