Lipoic acid effects on renal function, aminopeptidase activities and oxidative stress in Crotalus durissus terrificus envenomation in mice

Abstract

Crotalus durissus terrificus envenomation has been associated with direct nephrotoxicity, rhabdomyolysis, hyperuricemia, urinary hypoosmolality, alterations in aminopeptidase activities (AP) and oxidative stress. This study evaluated the effects of lipoic acid (LA) on renal function, lethality, AP and GSSG/GSH in mice injected with C. d. terrificus venom (vCdt). The doses and routes of administration of LA and vCdt promoted no systemic myotoxicity. LA did not alter significantly the lethality of vCdt. In nonenvenomed, LA induced hypercreatinemia, urinary hyperosmolality, decrease of urinary urea and creatinine, increase of protein in plasma and in soluble fraction (SF) and decrease in membrane-bound fraction (MF) of cortex and medulla. Decreased levels of all AP (except neutral-AP in MF-medulla) were also induced by LA in nonenvenomed. LA associated with vCdt decreased plasma osmolality, hematocrit, urinary uric acid, but increased urinary and SF-medullar protein. LA mitigated the increase of protein in SF-cortex and corrected hyperuricemia, GSSG/GSH and protein in MF-cortex and MF-medulla, as well as decreased plasma neutral AP and acid AP in MF-medulla of envenomed mice. Data suggest that LA contributes to the solubilization/remotion of proteins in MF with impairment of most AP, but it could be beneficial for the treatment of the direct nephrotoxicity of vCdt.