Vitamin E inhibits hepatic NF-kappaB activation in rats administered the hepatic tumor promoter, phenobarbital.
Phenobarbital (PB) is an efficacious hepatic tumor promoter. Although the promoting activity of PB is likely related to altered cell proliferation or apoptosis, the induction of an oxidative stress environment may also be important. PB has been shown to activate the transcription factor nuclear factor-kappaB (NF-kappaB). In this study, we hypothesized that PB-induced NF-kappaB activation can be decreased by dietary vitamin E in rats. Male Sprague-Dawley rats (n = 39) were fed a purified diet with varying levels of dietary vitamin E (10, 50 or 250 mg/kg of dl-alpha-tocopherol acetate) for 28 d, at which time 8 rats per level of dietary vitamin E were fed the same diet with 500 mg/kg PB for 10 d. In the rats fed the low vitamin E diet, PB increased NF-kappaB DNA binding, but it did not affect NF-kappaB activation in rats fed higher levels of vitamin E (50 and 250 mg/kg). Vitamin E may decrease the oxidative stress created by PB by also enhancing other antioxidants; therefore, we also measured hepatic glutathione S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase and NAD(P)H:quinone reductase (DT-diaphorase) activities and glutathione and ascorbic acid concentrations. Increased dietary alpha-tocopherol did not affect the antioxidants and antioxidant enzymes altered by PB treatment. Thus, the effect of alpha-tocopherol acetate on NF-kappaB activation does not appear to be mediated by alterations in the antioxidant system. These results demonstrate that the activation of NF-kappaB, a transcription factor that affects cell proliferation- and apoptosis-related gene expression, can be inhibited by dietary vitamin E.
D000818:Animals; D000975:Antioxidants / Q000032:analysis / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010634:Phenobarbital / Q000633:toxicity*; D011401:Promoter Regions, Genetic; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000032:analysis / Q000494:pharmacology*
D000975:Antioxidants; D002273:Carcinogens; D016328:NF-kappa B; D014810:Vitamin E; D010634:Phenobarbital