CIMETIDINE ENHANCES THE HEPATOPROTECTIVE ACTION OF N-ACETYLCYSTEINE IN MICE TREATED WITH TOXIC DOSES OF PARACETAMOL

Paracetamol, in toxic doses, is associated with extensive liver damage . This represents one of the common causes of morbidity and mortality in drug poisoning cases. This study was undertaken to investigate the possible potentiation of the hepatoprotective action of N-acetylcystei ne (NAC) by cimetidine (CMD), an inhibitor of hepatic microsomal oxida tive enzymes. The effects of NAC, cimetidine and the two in combinatio n, administered 2 h post-paracetamol dose, on mortality, plasma glutam ic oxaloacetic (GOT) and glutamic pyruvic (GPT) transaminase activitie s and hepatic reduced glutathione (GSH) levels were investigated in mi ce 24 h after treatment with a single oral dose of paracetamol (400 mg /kg). Both NAC and cimetidine caused a partial improvement of survival rate, plasma GOT and GPT activities. In addition, they prevented the depletion of hepatic GSH contents. However, concomitant administration of NAC and cimetidine produced a 100% survival rate and a marked redu ction in plasma GOT and GPT activities to within the normal range, whi le significantly raising hepatic GSH concentrations to values close to those measured in saline-treated control animals. It is therefore con cluded that cimetidine and N-acetylcysteine may have an additive hepat oprotective action in the treatment of paracetamol overdose. (C) 1997 Elsevier Science Ireland Ltd.