SUMMARY
Sarin is a potent inhibitor of acetylcholinesterase (AChE). It is known as an agent of chemical warfare and is one of a number of nerve agents misused for chemical terrorism, e.g. on the Tokyo subway attacks. Though effect of sarin on the cholinergic system is well-known, long-term adverse effects and the role of oxidative stress in sarin toxicity remain unknown. The experiment reported here was carried out on laboratory Wistar rats intramuscularly exposed to 0.5-50% of sarin LD50 for one hour. A complex biochemical examination of plasma samples and an assessment of oxidative stress in the liver, kidney, spleen, cerebellum and frontal lobe were performed after euthanasia of the animals. By means of these biochemical markers, we were able to observe the induction of hyperglycaemia in a dose-dependent manner. Other biochemical markers such as transaminases were influenced in a non-standard manner as sarin probably acted as an inhibitor of these markers. Oxidative stress markers and an assessment of AChE activity showed an unequal impact of sarin on different tissues. Significant inhibition of AChE was found in the cerebellum and frontal lobe. Besides this, alterations in reduced glutathione, ferric reducing antioxidant power (FRAP) and thiobarbituric acid reactive substances (TBARS) were proven. In particular, an accumulation occurred of reduced glutathione in the frontal lobe, whereas depletion of FRAP was found in the kidney and spleen, and a strong increase in TBARS occurred in the spleen in a dose-dependent manner. We infer that sarin extensively influences oxidative homeostasis. Surprisingly, the central nervous system seems to be more resistant than the other organs.
KEY WORDS
sarin; nerve agents; chemical warfare; acetylcholinesterase; oxidative stress; antioxidant; biochemistry
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