Plasma, urine and kidney aminopeptidases of mice induced by Crotalus durissus terrificus venom

Abstract

Envenoming by Crotalus snakes is an important public health problem, because it is responsible for high incidence of morbidity and mortality. The most common complication in accidents evoked by this snake genera is acute renal failure (IRA), which is characterized by a rapid decrease of renal functions. In Crotalus snakebite, IRA is related to rhabdomyolysis and also to direct nephrotoxic effect. Acid (APA), basic (APB), neutral (APN), cystyl (CAP), prolyl imino (PIP), pyroglutamyl (PAP) and prolyl dipeptidyl IV (DPPIV) aminopeptidases present high activity levels in renal tissue. Recently, our group demonstrated that renal damage caused by cyclosporin treatment promotes significant changes on these renal enzyme activities. The oxidative stress is known to occur in this kind of renal damage, which has been reported to be reduced by agents such as lipoic acid and simvastatin. The aim of this study is to investigate whether the venom of one of the terrestrial snake responsible for a high rate of snakebite accidents in Brazil, the rattlesnake Crotalus durissus terrificus, at an effective dose to cause IRA, elicite changes: (I) on the aforementioned plasma, urinary and renal cortical and medullar aminopeptidase activities, and (II) promote oxidative stress; as well as (III) if these changes can be reduced by lipoic acid and/or simvastatin administration. The results of this study may help the understanding about mechanisms and consequences of nephrotoxic effects of this venom, mainly on renal peptidergic systems, as well as to evaluate the possibilities that any of the plasma and/or urinary aminopeptidase activities under study are nephrotoxicity markers, and whether lipoic acid and simvastatin could be a new coadjuvant agents to be introduced within the antivenom therapy.