Induction of drug-metabolizing enzymes and toxicity of trans-stilbene oxide in rat liver and kidney

The effect of trans-stilbene oxide (TSO) on organ function and morphology and on drug-metabolizing enzymes was determined in male Sprague-Dawley rats. TSO (300 or 600 mg/kg) was administered i.p., once daily for 5 consecutive days. At a dose of 300 mg/kg, TSO did not alter body weight, but increased liver weight. The higher dose (600 mg/kg) markedly decrease body weight. TSO treatment (300 mg/kg) induced several drug-metabolizing enzymes. Epoxide hydrolase actity was enhanced in the liver, kidney and lung. In contrast, arylhydrocarbon hydroxylase activity was not significantly altered. Glutathione S-transferase, with 1-chloro-2,4-dinitrobenzene as substrate, and uridine diphosphoglucuronyl transferase activity, with p-nitrophenol as substrate, were also increased in the liver and kidney after TSO treatment. It appears that TSO induces hepatic and renal enzyme activities in a similar manner. Treatment with the higher dose of TSO depressed accumulation p-amino-hippurate by renal cortical slices and increased blood urea nitrogen concentration. Histological examination of kidney sections after treatment with TSO revealed no abnormality. The lower dose led to negligible alteration in liver and the higher dose resulted in mild to moderate hepatic cellular changes. Thus, 5 days of treatment with TSO at a dose of 300 mg/kg/day appears to induce drug-metabolizing enzyme activities without altering functional and histological integrity of the liver and kidneys, suggesting that like phenobarbital and 3-methylcholanthrene, TSO may be a useful tool in elucidating the functional role of drug metabolizing enzymes in these organs.