Plasma, urinary and renal aminopeptidases in mice injected with Bothrops jararaca and Crotalus durissus terrificus venoms

Abstract

Envenoming by Bothrops and Crotalus snakes is an important public health problem, because is responsible for high incidence of morbidity and mortality. The most common complication in accidents evoked by both snake genera is acute renal failure (IRA), which is characterized by a rapid decrease of renal functions. In Bothrops snakebite, IRA is related to renal ischaemia, coagulation disorders and direct nephrotoxic effect, while 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 lipoic acid and simvastatin. The aim of this study is to investigate whether the venoms of the two terrestrial snakes responsible for the majority of snakebite accidents in Brazil, the pit viper Bothrops jararaca and 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 or simvastatin administration. The results of this study may help the understanding about mechanisms and consequences of nephrotoxic effects of these venoms, mainly on renal peptidergic systems, as well as to evaluate the possibilities that any of plasma and/or urinary aminopeptidase activities under study are nephrotoxicity markers, and that lipoic acid and simvastatin could be new coadjuvant agents to be introduced within the antivenom therapy. (AU)