Effects of Antidotes on the Hepato- and Nephrotoxicity of Paracetamol in the Rat

Abstract

During intoxications with paracetamol hepatic and renal failure may develop, the latter also in the absence of liver damage (Boyer et al., 1971; Prescott et al., 1971; Cobden et al., 1982). Several antidotes are available for the treatment of severe paracetamol poisoning, these include mainly precursors of GSH-synthesis like methionine or N-acetylcysteine (Crome et al,. 1976; Prescott et al., 1977). In animal experiments diethyldithiocarbamate (dithiocarb) was shown to be an effective antidote against paracetamol-induced hepatotoxicity, due to its strong inhibitory influence on microsomal monooxygenases (Strubelt et al., 1974; Siegers et al., 1982). No experimental or clinical data, however, are available proving the efficacy of these antidotes in preventing paracetamol-induced renal damage. Moreover, it is still unclear, whether the metabolic pathways leading to hepatotoxic intermediates of paracetamol are the same for exerting nephrotoxic response.