Nafenopin, a peroxisome proliferator, depletes hepatic vitamin E content and elevates plasma oxidised glutathione levels in rats.

Male Sprague-Dawley rats were given oral doses of nafenopin (80 mg/kg/d) for up to 28 d. Nafenopin administration resulted in liver enlargement and induction of peroxisomal fatty acid beta-oxidation enzymes (which generate hydrogen peroxide), but little effect was observed on catalase and cytosolic GSH peroxidase was decreased. Hepatic vitamin E levels were depleted to around 50% of control. A small increase in hepatic oxidised glutathione (GSSG) content was paralleled in a time-dependent increase in plasma GSSG. These changes in vitamin E and GSSG levels may represent early indicators of oxidative stress produced in rat hepatocytes by nafenopin and other peroxisome proliferators as a consequence of the increased production of hydrogen peroxide.