THERAPEUTIC APPLICATIONS OF ANIMAL VENOM
Poison, Toxin, Venom
• Poison - Any substance which - if ingested or absorbed by the body even in the smallest quantity - can cause harm by means of chemical reaction. Causation of this harmful chemical reaction is termed as "poisoning". For example - food poisoning. Poisons are often labeled as "harmful" or "hazardous". [1]
• Toxin - Any natural or artificial substance that causes a poisonous reaction inside the body can be termed as a "toxin". Toxins are a sub-category within poisons. In other words, all toxins are poisons, but all poisons are not toxins. Toxins can comprise of peptides, proteins, small molecules, etc. Toxins are capable of producing diseases in living organisms. For example, tetanus is caused by toxins produced by the microorganism Clostridium tetani. [2]
• Venom - Those toxins which are produced in a specialized gland within the body and delivered specifically by means of a bite or a sting are termed as "venoms". Production and release of venom is a defense mechanism adapted by various animals. A venom causes harm only IF it is "injected" into the bloodstream, whereas a poison causes harm if it is merely "ingested" or "absorbed" by the body. [3]
Sources of Animal Venom
The main sources of animal venom are as follows - [4]
• Invertebrates - Black widow spider, scorpions, wasps, centipedes, bees, some varieties of caterpillars, ants, jellyfish, etc.
• Aquatic organisms - Stingrays and other fishes
• Reptiles - Snakes, certain varieties of lizards, salamanders and monitor lizards
• Mammals - Male platypus, shrews, slow loris, etc.
Animal Venom as Therapy - How and Why?
Animal venom is the source for a large variety of therapeutic drugs despite its potent lethality.
Venoms are toxic in nature as a large number of toxins present in the venom act in a synergistic manner, and produce the desired effect. However, the toxins by themselves may not be necessarily harmful in an individual capacity. When these toxins are individually injected into the body at small doses, they have the potential to display therapeutic effects such as action against pain and heart dysfunction.
Animal venoms are a hugely untapped source of potential therapies against a wide variety of pathological conditions such as cancer, diabetes, cardiovascular disorders, etc. Another advantage of using venom as therapy is that venoms possess extremely high specificity. This property enables venom to be used as therapeutic drugs with high target efficacy and high target selectivity. [5]
Animal venom has also been found to be extremely successful and precise with regards to regulating certain bodily functions. Certain components in animal venom can either be individually harvested or altered such that the venom can be used for therapeutic purposes. [6]
Medical science and healthcare have made great strides with regards to drug development and drug therapy. However, in the current scenario, there are plenty of "unmet" medical needs, and newer therapies are required to counter conditions such as cancer, diabetes, etc. Drug safety and rising research costs are major issues within the pharmaceutical industry even today. Under such circumstances, it is necessary to explore novel, innovative, and unique methods of drug therapy so as to meet growing medical needs.
Use of animal venom as therapy is one such method which needs to be explored to a great extent.
European scientists have started a programme called "Venomics", whose main aim is to analyze the potential applications of animal venom in the medical field. Only about 3500 animal toxins have been studied out of the existing 43 million animal toxins in nature. [5]
Animal Venom - Therapeutic Applications
• Antivenom- This is the most common application of animal venom with regards to drug therapy. Antivenom is used for treating snake bites or insect stings. Antivenom is produced by extracting venom from an animal, diluting it, and injecting it into a sheep, horse, or a goat. Antibodies are produced against this injected venom due to immune response. These antibodies are then harvested and used as therapy against venom, thus called "antivenom". The principle of the functioning of antivenom is the same as the principle of functioning of vaccines. [7]
• Anti-Cancer - Toxins extracted from certain animals contain compounds which possess anti-cancer activity. If these compounds are isolated and individually harvested, animal venom can prove to be a great source of anti-cancer drugs.
The deathstalker scorpion is venomous in nature - the venom extracted is neurotoxic in nature, and causes death by pulmonary oedema. However, the toxin extracted from the deathstalker scorpion has a chemical known as chlorotoxin (it is non-toxic despite its name). Chlorotoxin has been found to an extremely effective therapy for treating brain cancer. [8]
Halichondrin B is a toxin isolated from the sponge Halichondria okadai and appears to interfere with the functioning of the microtubules in cancerous cells in the case of melanoma and leukaemia cells. [9]
The venom extracted from copperhead snakes contains a protein called contortrostatin, whose properties are currently being studied for its viability against cancer cells, preventing the spread of breast cancer, and inhibition of ovarian cancer in humans. [10]
A protein called eristostatin is present in the venom of the Asian sand viper, which when extracted enhances the immune system to fight against malignant melanoma. It has been found that eristostatin prevents metastasis of cancer cells into the liver and lungs. [11]
Toxins extracted from bees are known as apitoxins. A protein present in apitoxin is called melittin which causes inflammation after bee stings. However, melittin can be altered such that functional changes would render it to be used as an effective anti-cancer agent. Melittin can also be used to anti-cancer drugs to the affected cells, while not harming normal cells. Research is currently underway to study the effectiveness of melittin as a cytotoxic, antitumour, and apoptotic agent. [12]
Bee venom has also been found to display lethality against human T-cell lymphoblastic leukaemia cell line. Therefore, bee venom has great potential to be used as a potent anti-cancer therapy against T-cell leukaemia, either singularly or in a combination with other chemotherapeutic drugs. [13]
The venom extracted from the scorpion Buthus martensii Karsch has been found to contain a component which inhibits proliferation of human leukaemia cells. [14]
Venom harvested from scorpions can be combined with a fluorescent biomarker Cy5.5, which when injected possesses the ability to distinguish between a normal cell and a cancerous cell. This development has the potential to increase the efficacy and specificity of cancer chemotherapy to a great extent. [15]
Nanoparticles of gold, silver, iron, etc. have been studied for their potential use as a means of venom drug delivery machinery. Bombesin is a toxin present on the skin of the European fire-bellied toad. When Bombesin is embedded on the surface of gold nanoparticles, it affixes itself to cancers of the prostate, breast, and lung. As a result, the tumour shrivels and dies. [16]
• Therapy for muscular dystrophy - Venom extracted from the Chilean rose tarantula contains a peptide called GsMtx-4. This peptide has been found to turn off ion channels in muscular cells, which decreases muscular stress. One of the reasons for occurrence of muscular dystrophy is increased mechanical pressure on muscles. A synthetic version of GsMtx-4 has been prepared which improves muscular activity in patients suffering from muscular dystrophy. [17]
• Painkiller- A synthetic compound called Prialt has been produced which is identical to the toxins found in cone snail venom. Prialt has been much more effective at fighting pain than morphine, and it does not possess the addictive properties of morphine. [18]
Mamabalginsare proteins isolated from the venom of the black mamba snake. These proteins are as effective as morphine for blocking pain, and produce lesser side-effects. [19]
• Anti-diabetic- The Gila monster is a highly venomous lizard. The saliva of the Gila monster contains a component that can regulate insulin production in the case of diabetics. This component (extracted from the saliva of the Gila monster) is used in a drug called Byetta, which helps regulate insulin levels in diabetics. [20]
• Anti-hypertensive - Venom extracted from the Brazilian arrowhead viper contains bradykinins, which is related to a group of drugs called ACE inhibitors, for treating hypertension and heart failure. [21]
• Blood coagulation and anticoagulation - Toxins extracted from the venoms of various snakes possess both procoagulant and anticoagulant action, which are highly useful for treatment of clotting disorders as well as removal of blood clots within vascular tissues present in the body. [22]
References
1. http://en.wikipedia.org/wiki/Poison
2. http://www.omg-facts.com/Science/Poison-Toxin-And-Venom-Are-Three-Complet/52899
3. http://en.wikipedia.org/wiki/Venom
4. http://en.wikipedia.org/wiki/Venom#Diversity
5. http://www.venomics.eu/articles/VENOMICS_press_kit.pdf
6. http://ngm.nationalgeographic.com/2013/02/125-venom/holland-text
7. http://en.wikipedia.org/wiki/Antivenom
8. http://prezi.com/1eduhhaji8j7/ap-chemistry-chlorotoxin/
9. http://www.jbc.org/content/266/24/15882.long
10. http://www.cancerdefeated.com/newsletters/Snake-Venom-New%20Hope-For-Cancer-Treatment.html
11. http://www.economist.com/news/science-and-technology/21569015-snake-venom-being-used-cure-rather-kill-toxic-medicine
12. http://www.ncbi.nlm.nih.gov/pubmed/22109081
13. http://www.jvat.org/content/19/1/25
14. http://www.mskcc.org/cancer-care/herb/scorpion-venom
15. http://www.independent.co.uk/news/science/scorpion-venom-offers-improved-cancer-surgery-457443.html
16. http://www.npep.co.za/index.php?option=com_content&view=article&id=108:from-devils-to-darlings-how-we-use-venoms-toxins-and-nanotechnology-to-save-lives&catid=2:newnano&Itemid=18
17. http://www.buffalo.edu/content/shared/university/news/news-center-releases/2012/12/005.html
18. http://news.discovery.com/human/snail-venom-painkiller.htm
19. https://www.sciencenews.org/article/black-mamba-bite-packs-potent-painkiller
20. http://www.sciencedaily.com/releases/2007/07/070709175815.htm
21. http://www.oncologynews.biz/pdf/sep_oct_13/123_ONSO13_Amphibian.pdf
22. http://www.ncbi.nlm.nih.gov/pubmed/20685219
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Therapeutic Applications of Animal Venom
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