Phenobarbital increases rat hepatic prostaglandin F2 alpha, glutathione S-transferase activity and oxidative stress.
Eight-week-old female F344/N rats were fed 3.0 or 6.0% of calories (kcal%) as linoleate with or without 0.05% phenobarbital (PB) for 35 days. PB treatment increased glutathione S-transferase (GST) activity by 80% and prostaglandin (PG) F2 alpha levels 4-fold (p less than 0.05). PB decreased hepatic alpha-tocopherol significantly. Hepatic linoleate was decreased by PB in rats fed 6 kcal% but not 3 kcal% linoleate. Increased dietary linoleate had no significant effect on hepatic PGF2 alpha or alpha-tocopherol levels or GST activity. This study suggests that PB hepatotoxicity and tumor-promoting ability may be mediated, at least in part, by PGF2 alpha. PB's effect on PGF2 alpha could be a result of both GST-mediated prostaglandin synthesis and oxidative stress. The removal of significant amounts of hepatic alpha-tocopherol during oxidative stress induced by PB might diminish endogenous inhibition of hepatic PG synthesis by a-tocopherol.
Hendrich
S
S
Department of Food Science and Human Nutrition, Iowa State University, Ames 50011.
Krueger
S K
SK
Chen
H W
HW
Cook
L
L
D000818:Animals; D000975:Antioxidants; D015237:Dinoprost / Q000378:metabolism*; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism*; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009929:Organ Size; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D014810:Vitamin E / Q000378:metabolism*
D000975:Antioxidants; D008041:Linoleic Acids; D014810:Vitamin E; D019787:Linoleic Acid; D015237:Dinoprost; D005982:Glutathione Transferase; D010634:Phenobarbital