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Snake Venom

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Introduction

Summary Videos

History

Evolution of Venom

Interesting Venom/Snake Facts

There are 8000 venomous snake bites are reported in USA every year, out of which, only five bites are fatal (Nielson, n.d). Copperhead snake accounts for the majority of the venomous snake bites in USA.India is the most affected by venomous snake bites and has 35000-50000 deaths every year from snake bites. Pakistan ranks second in terms of fatalities with 8200 reported annually. Snakes are known to consume their prey much larger than their own size and this is known as jaw-walking. Their jaws are only loosely attached to their skull and are unconnected, implying that they work independently. Snakes have curved teeth which allow them to pull and swallow the animal further. Snakes are also known to play a vital role in the environment by maintaining populations of rodents and allow high crop yields in farms (Nielson, n.d). Snakes normally prey small animals including fish, frogs, snails, lizards, chickens, mice, rats or sometimes, they even attack other snakes (Kang et al., 2011). Venom is their primary offensive weapon and is used to incapacitate and immobilize the prey. The secondary function is to use it in a defense mechanism against the predator and also to aid in digestion (Kang et al., 2011).

Source: http://www.venomoussnakes.net/

How To Identify Venomous Snakes

Methods of Venom Injection

Chemistry

Venom gland is a modified version of a salivary gland and in a snake, it is located behind and under the eye (Johnson, 2012). Sea snakes, cobra and krait contain neurotoxins, which are the most powerful, resulting in muscle paralysis in victim and resulting in death (Tu, 1996). Rattlesnake venoms have tissue damaging toxins like myonecrotic and hemorrhagic toxins. This produces muscle damage in tissues and organs along with dysfunctioning or loss of body part. Although neurotoxins are most powerful, there are other dangerous toxins such as cardiotoxins, myotoxins and cytotoxins (Tu, 1996). Different snake species have different toxins in their venom (Casewell et al., 2014). This is due to different toxin-encoding genes in the snake’s venom gland or the genome. The primary constituents of snake venom include proteins and peptides also known as toxins and they are encoded by approximately 5-10 multilocus gene families (Casewell et al., 2014). These different venoms have evolved over a long time to become a complex mix of pharmacologically active peptides, aiding them in prey capture (Kang et al., 2011). Snake venoms contain 30 to more than 100 protein toxins exhibiting enzymatic and non-enzymatic activities. Some common enzymes identified in snake venom include phospholipase A2s (PLA2s), serine proteinases, metalloproteinases, acetylcholinesterases (AChEs), l-amino acid oxidases, nucleotidases (5¢-nucleotidases, ATPases, phosphodiesterases and DNases) and hyaluronidases. AChE is largely found in venomous snakes that belong to family Elapidae. L amino acid oxidase inhibit aggregation of platelets. Some studies performed in 1990s demonstrated that snake venom induces apoptosis in endothelial cells and this is probably due to an increase in H2O2 concentrations (Kang et al., 2011). Spla2S types 1 and 2 are found in snake venoms, particularly in those of elapids and sea snakes (Harris & Scott-Davey, 2013). Alongside proteases, phospholipases, neurotoxins are shown to immobilize the prey, haemotoxins are shown to inhibit coagulation and allow circulation of incoagulable blood (Harris & Scott-Davey, 2013). Nucleotidases found in snake venoms generate purines, mostly adenosine, and liberate adenosine to aid in prey immobilization(Dhananjaya & D’Souza, 2010) . The quantity of venom in the venom gland is directly correlated to the snake’s size and increases exponentially with the snake’s size (Johnson, 2012). Venom quantity can range from 1 mg to 850 mg, with the largest amount of venom in an Eastern Diamondback rattlesnake. It is also interesting to note that the delivery of venom is a voluntary action and all venomous snakes are equally capable of delivering dry bites (Johnson, 2012).

A snake first accurately assesses the target on three levels before it injects venom (Young, Lee, & Daley, 2002). The situation of the encounter such as defensive or predatory, the size of the target and the type of target. A snake uses various cues to initiate its predatory behaviour such as chemosensory, visual and thermal. Rattlesnakes are shown to increase the quantity of venom injected based on the size of the target and inject more venom when they bite a larger target. They were shown to inject twice the amount of venom into large mice, 25g to 44g, than in medium sized mice, 7g to 11g (Young et al., 2002).

Classification

Mechanisms of Actions of Toxins

Determining Venom Toxicity

To determine the toxicity of a specific sample of venom, a LD-50 (also known as median lethal dose) test can be done. This test was developed in 1927 originally used for biological standardization of dangerous drugs (Zbeinden and Flury-Roversi, 1981). Eventually the test was used to also test toxicological properties of other chemical compounds (Zbeinden and Flury-Roversi, 1981). This test involves finding out the required dose of a substance to kill half the members of a population of tested species over a specific duration of time. The value that is obtained from the test is considered to not be a biological constant as the results are influenced by many factors of the animals and the more animals the accurate (Zbeinden and Flury-Roversi, 1981). By performing this test, you can determine how toxic the venom from a specific species is. You can determine how much is required in order for a human or any other specie to die.

Physiological Effects

Depending on the species that bites you, you may experience different symptoms. Generally, an individual will have two puncture wounds from the fangs of the snake. Around the bite there will be some swelling and redness that begins to form (HealthLine). Around this area, pain will also be felt by the individual (HealthLine). They will experience some difficulty breathing, vomiting, nausea, blurred vision, sweating, salivating and numbness in the face and limbs (HealthLine). These are the symptoms felt from most snake bites, the common symptoms. Other various symptoms will be experienced by other species of snake, for example, rattlesnakes, coral snakes, copperheads, etc (HealthLine). Many species of snake contain venom that will interfere platelet aggregation which is an important process in thrombosis (blood coagulation) and hemostasis (a process that stops bleeding after an injury) (Kini and Evans, 1990).

Use of Snake Venom To Treat Disease

Snake venoms consist of a complex mixture of several biologically active proteins, peptides, enzymes, organic compounds and inorganic compounds (Vyas et al., 2013). One use of venom that has been studied to see for future use is in the area of cancer. It has been discovered that snake venom can inhibit cell proliferation and also promoting cell death in regards to cancer cells (Vyas et al., 2013). These processes occur due to increased calcium ion influx, decreasing or increasing the expression of proteins that control the cell cycle resulting in damage to the cell membrane, apoptosis induced cancer cells, promoting cytochrome C release, etc (Vyas et al., 2013). Certain proteins from snake venom have also been used to create drugs that help thrombin inhibition, blood thin, fibrinogen inhibition for strokes, help with high blood pressure, etc. (Koh et al., 2006).

Immunity

Traditional Venom Treatments

Colonial remedies were quite different from the current treatment for venomous snake bites. A case in 1868 revealed some of these methods when a man was bitten by a venomous snake (Hobbins, 2017). The surgeon was tied a ligature around the patient’s arm to cut the site of bite. He then poured ammonia on the wound site in an attempt to neutralize the venom and then made the patient drink six ounces of brandy to rouse his circulation. The surgeon next proceeded by waving a powerful smelling salt under the patient’s nose and subsequently applied a mustard poultice to his abdomen, hands and feet to ease internal congestion. Another medical professor then injected ammonia into one of his veins in the bitten arm and surprisingly, saved the patient’s life. In addition to this scenario, traditional venom treatments commonly included suction or ligature to expel the venom and limit further circulation in the bloodstream (Hobbins, 2017). Furthermore, medicinal plants are also commonly used to treat venomous snake bites, as they are safe, effective, inexpensive and attainable from neighbouring forests (Gupta & Peshin, 2012). For example, Vitis vinifera L. seeds are extracted and used due to their neutralization effects of edema, from viperine snake bites (Gupta & Peshin, 2012).

Current and Future Studies

Conclusion

References

Casewell, N. R., Wagstaff, S. C., Wüster, W., Cook, D. A. N., Bolton, F. M. S., King, S. I., … Harrison, R. A. (2014). Medically important differences in snake venom composition are dictated by distinct postgenomic mechanisms. Proceedings of the National Academy of Sciences, 111(25), 9205–9210. https://doi.org/10.1073/pnas.1405484111

Dhananjaya, B. L., & D’Souza, C. J. M. (2010). The pharmacological role of nucleotidases in snake venoms. Cell Biochemistry and Function, 28(3), 171–177. https://doi.org/10.1002/cbf.1637

Gupta, Y. K., & Peshin, S. S. (2012). Do Herbal Medicines Have Potential for Managing Snake Bite Envenomation? Toxicology International, 19(2), 89–99. https://doi.org/10.4103/0971-6580.97194

Harris, J. B., & Scott-Davey, T. (2013). Secreted Phospholipases A2 of Snake Venoms: Effects on the Peripheral Neuromuscular System with Comments on the Role of Phospholipases A2 in Disorders of the CNS and Their Uses in Industry. Toxins, 5(12), 2533–2571. https://doi.org/10.3390/toxins5122533

Hobbins, P. (n.d.). Hissstory: how the science of snake bite treatments has changed. Retrieved November 25, 2017, from http://theconversation.com/hissstory-how-the-science-of-snake-bite-treatments-has-changed-71408

Johnson, s. (2012). Venomous Snake FAQs. Ufwildlife.ifas.ufl.edu. Retrieved 25 November 2017, from http://ufwildlife.ifas.ufl.edu/venomous_snake_faqs.shtml

Kang, T. S., Georgieva, D., Genov, N., Murakami, M. T., Sinha, M., Kumar, R. P., … Kini, R. M. (2011). Enzymatic toxins from snake venom: structural characterization and mechanism of catalysis. FEBS Journal, 278(23), 4544–4576. https://doi.org/10.1111/j.1742-4658.2011.08115.x

Nielsen, A. Venomous Snakes - facts, species, bites and natural history. Venomoussnakes.net. Retrieved 24 November 2017, from http://www.venomoussnakes.net/

Tu, A. T. (1996). Overview of snake venom chemistry. Advances in Experimental Medicine and Biology, 391, 37–62.

Young, B. A., Lee, C. E., & Daley, K. M. (2002). Do Snakes Meter Venom? BioScience, 52(12), 1121–1126. https://doi.org/10.1641/0006-3568(2002)052[1121:DSMV]2.0.CO;2

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