Elimination of thioethers following administration of naphthalene and diethylmaleate to the rhesus monkey

As a measure of glutathione (GSH) conjugation, urinary, fecal and biliary excretion of thioethers and hepatic GSH content were measured in rhesus monkeys following administration of single doses of naphthalene and diethylmaleate (DEM). Naphthalene had little or no effect on hepatic GSH content and the excretion of thioethers into urine, feces or bile of rhesus monkeys which is similar to that observed in chimpanzees and humans and is in contrast to results obtained from rats. Apparently, conjugation of naphthalene and/or its metabolites with GSH does not play a major role in the metabolism of naphthalene in primates, whereas it is one of the major pathways in rodents. Rhesus monkeys, like chimpanzees, excreted about 13% of the various doses of DEM (30, 75 and 200 mg/kg) as thioethers into urine which is half of that excreted by rats. Six hrs after administration of 200 mg/kg DEM, the hepatic GSH content was decreased by 90% in the rhesus monkey. During the first day after this dose (200 mg/kg), the increase in the excretion of thioethers into bile corresponded to about 15% of the dose of DEM administered. Since fecal excretion of thioethers corresponded to only 1% of the dose and urinary excretion represented 12% of the dose, it appears that biliary thioethers of DEM are reabsorbed from the intestine and then excreted into urine. It appears that the rhesus monkey as well as the chimpanzee is, whereas the rat is not, a good animal model to study GSH-related conjugation reactions with predictive value for man.