ENZYMATIC CHANGES IN SNAKE ENVENOMATION- AN OBSERVATIONAL STUDY

Abstract

Sidharth Kapoor1

BACKGROUND
Snakes are the most feared and the most worshipped living creatures on the earth. Snakes are called venomous when envenomation or human fatalities after their bite are known. Snakebite is an acute medical emergency faced by temperate and tropical regions with heavy rainfall and humid climate. The specific therapy for snakebite in India is still polyvalent ASV and clinical practice ASV is not recommended until the victim of snakebite presents either with the evidence of bite by a poisonous snake such as definite fang marks, swelling or pain at the bite site or with clinical or laboratory evidence of envenomation such as local and systemic bleeding. In some cases, institution of ASV may also be initiated on the identification of offending snake brought by the patient or attendants, but most of these are subjective matters and subject to fallacies. Also, that out of polyvalent and monovalent ASV available, since it is monovalent ASV, which is desirable due to its less side effects and more effectiveness, but its use warrants the identification of snake, which is practically not possible in every case and/or on the objective evidence of peripheral neurological signs and symptoms and haematological alterations, which may not be dependable in many cases.
MATERIALS AND METHODS
Snake envenomation is in fact a multifactorial stress phenomenon, which produces altered physiological states including death and one of the consequences of the stress phenomenon is generation of several lysosomal enzymes and formation of free radicals. Extensive data search on Medline has failed to show study of this type in any part of the world, so this study being taken up as a preliminary attempt to evaluate the pattern of enzymatic changes in snake envenomation.
RESULTS
The patients included in the study were be those coming to the Emergency Department of Government Medical College, Jammu, bitten by poisonous snakes during the period May 2003 to April 2004. The case were worked up according to proforma. Both neurotoxic and haemotoxic snakebite cases were included and samples were taken on day 0 and day 4. For comparison, blood samples from healthy persons were be tested for the enzymes like ACP, ALP, AST, ALT, malondialdehyde, superoxide dismutase, serum bilirubin (conjugated and unconjugated) to establish a control group.
Haemotoxic Cases- Amongst 32 haemotoxic cases in which enzymatic assays were studied on day 0 and day 4 following conclusions were drawn- AST level was elevated significantly on day 0 and it registered a further rise on day 4 as compared to age-matched healthy control. Mean AST levels in 32 haemotoxic cases was 57 IU/L on day 0, but on day 4, the mean AST levels was 94 IU/L as against the control means of 25 IU/L. ALT level was significantly high on day 0. On day 4, a further rise in its level was found as compared to age-matched healthy control. Mean ALT levels on day 0 was 73 IU/L, and on day 4, it was 83 IU/L against the control mean of 23 IU/L. Acid phosphatase showed a rise of about two-fold on day 0, while on day 4, a four-fold rise was there as compared to age-matched healthy controls. Mean acid phosphatase levels on day 0 was showing two-fold increase (5.8 KA units), but on day 4, the mean levels rose further to 8.3 KA units; the control mean being 2.4 KA units. Alkaline phosphatase was elevated on day 0, but on day 4, its levels showed a downward trend, although normalisation was not achieved. Mean alkaline phosphatase level on day 0 was 920 IU/L, and on day 4, it was 360 IU/L against the control mean of 179 IU/L. Significant superoxide dismutase activity suppression was found on day 0, but on day 4, this activity were restored to some extent, but normalisation was not achieved. About 38% suppression in mean SOD activity on day 0 (22.37 IU/L), but on day 4, the levels increased and mean SOD activity suppression was only 8% (33.47 IU/L); the control mean being 36.99 IU/L. Significantly, higher levels of malondialdehyde, an in vivo marker of lipid peroxidation was achieved on day 0, but on day 4, the levels showed a downward trend, although control value could not be achieved.
In Neurotoxic Cases- Amongst 12 neurotoxic cases in which enzymatic assay was studied on day 0 and day 4, following conclusions were drawn. On day 0, both AST and ALT registered a rise of approximately three-fold, but on day 4, the levels showed a downward trend, although a two-fold rise was still found (on day 4) as compared to age-matched healthy controls. The mean serum AST levels on day 0 and day 4 were 57 IU/L and 73 IU/L respectively against a control mean of 23.5 IU/L. Mean serum ALT levels on day 0 and day 4 was found to be 73 IU/L and 57 IU/L respectively against control mean of 24.3 IU/L. ACP levels were elevated on day 0, but on day 4, a further rise in levels was found. Acid phosphatase on day 0 and day 4 was 4.08 KA units and 5.3 KA units, respectively against control mean of 2.58 KA units. The ALP levels were elevated on day 0 and no significant fall on day 4 was found. Mean alkaline phosphatase levels on day 0 and day 4 was 387 IU/L and 365 IU/L respectively against a control of 200 IU/L. The SOD activity suppression on day 0 and day 4 was found to be nonsignificant. The MDA activity rise was significant on day 0, but on day 4, the levels were considerably reduced to achieve the value similar to those in the control levels. There was two-fold mean rise (6.53 mmol/L) in 32 haemotoxic cases on day 0, but on day 4, the mean levels reduced to 4.71 mmol/L, which was still higher than the control mean (3.27 mmol/L). In all 12 neurotoxicity cases were studied, the SOD activity suppression on day 0 and on day 4 was found to be statistically nonsignificant. The MDA levelson day 0 showed a rise, which was less than two-fold (5.80 mmol/L), and on day 4, the mean levels were reduced to 3.27 mmol/L.
CONCLUSION
It was found that the mean rise in AST level was higher in neurotoxic cases than in haemotoxic cases on day 0, but on day 4, haemotoxic cases had still higher levels, but the value of AST had trend towards normalisation in neurotoxic cases. Since the mortality figures were too low to perform statistical analysis, the prognostic value of these changes could not be determined, hence, a larger study will be more informative. Since there is only one study available in literature in which effect of viperine venom enzymatic changes on male albino rats was studied, no definite conclusions could be drawn on the clinical studied, no definite conclusions could be drawn on the clinical implications of such changes in enzymatic assay after snake envenomation in human beings. Secondly, it is still not clear whether the oxidative stress after snake envenomation is because of effect on venom or is just on epiphenomenon, therefore, further work of similar nature is required before drawing definite conclusion.

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