Effect of potassium ethylxanthogenate on the acetaminophen hepatotoxicity in mice.

The effects of potassium ethylxanthogenate (PEX), acetaminophen (AAP) and their combination on the activity of serum transaminases, liver glutathione level and the activity of some drug metabolizing enzyme systems in male albino mice are studied. PEX (80 mg/kg p. o.), applied one hour before AAP (737.5 mg/kg p. o.) or simultaneously with it, prevents the AAP-induced rise in transaminases. PEX reduces significantly the AAP-induced depletion of the liver glutathione. Eighteen hours after the administration of a hepatotoxic dose of AAP, there is a statistically significant decrease of the activity of aniline hydroxylase, ethylmorphine demethylase, uridine diphosphoglucuronyl transferase, glutathione-S-transferase, NADPH-cytochrome-c-reductase, the P-450 content and a 5-fold increase of TBA-reactive products. PEX, introduced one hour before AAP or simultaneously with it, prevents these changes. The basic mechanism through which PEX reduces the liver toxicity of AAP is assumed to be the decrease in the amount of toxic metabolite formed.