Zh. Almustafa et al., CIMETIDINE ENHANCES THE HEPATOPROTECTIVE ACTION OF N-ACETYLCYSTEINE IN MICE TREATED WITH TOXIC DOSES OF PARACETAMOL, Toxicology, 121(3), 1997, pp. 223-228
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.