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.
Lake
B G
BG
British Industrial Biological Research Association (BIBRA), Carshalton, Surrey, U.K.
Gray
T J
TJ
Körösi
S A
SA
Walters
D G
DG
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D005978:Glutathione / Q000097:blood*; D008099:Liver / Q000032:analysis / Q000187:drug effects*; D008297:Male; D008830:Microbodies / Q000187:drug effects*; D009255:Nafenopin / Q000633:toxicity*; D010084:Oxidation-Reduction; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D014810:Vitamin E / Q000032:analysis*
D011422:Propionates; D009255:Nafenopin; D014810:Vitamin E; D005978:Glutathione