Effects of vitamin E on the NF-κB pathway in rats treated with the peroxisome proliferator, ciprofibrate

Karen G. Calfee-Mason, Brett T. Spear, Howard P. Glauert

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Peroxisome proliferators (PPs) are a diverse group of nongenotoxic compounds, which induce hepatic tumors in rodents. The mechanisms leading to hepatic tumors have not been elucidated, but oxidative stress may play a role in the process. Previous studies in our laboratory have shown that peroxisome proliferators activate the transcription factor nuclear factor-kappa B (NF-κB) and that this activation is mediated at least in part by oxidative stress. We therefore hypothesized that increased dietary vitamin E would decrease NF-κB DNA binding in rodents treated with ciprofibrate (CIP). In this study, 36 male Sprague-Dawley rats were fed a purified diet containing varying levels of vitamin E (10, 50, 250 ppm α-tocopherol acetate). After 28 days on the purified diet, seven animals per vitamin E group received 0.01% CIP in the diet for 10 days. Electrophoretic mobility shift assays (EMSAs) showed that CIP treatment increased DNA binding of NF-κB. Increased dietary α-tocopherol acetate inhibited CIP-induced NF-κB DNA binding. Because NF-κB translocates to the nucleus upon the phosphorylation and degradation of inhibitor of IκB, we also used Western blots to measure cytosolic protein levels of IκBα and IκBβ, and the IκB kinases, IKKα and IKKβ. IκBα protein levels were decreased in all three CIP-treated groups, with the 10 ppm vitamin E diet also decreasing IκBα levels in control rats. No difference in IκBβ protein levels was observed among any of the groups. The CIP-treated rats generally had lower protein levels of IKKα and IKKβ. This study supports our working hypothesis that an increased antioxidant environment can inhibit CIP-mediated NF-κB induction.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalToxicology and Applied Pharmacology
Volume199
Issue number1
DOIs
StatePublished - Aug 15 2004

Bibliographical note

Funding Information:
The authors thank Job Tharappel, Dmitriy Kaganov, David Peyton, Karen Conon, and Amy Wilson-Ellis for their assistance with the animal study. This work was supported by National Cancer Institute Grants CA-74147 and CA-01688 and by the Kentucky Agricultural Experiment Station. K.C.M. was supported by a National Institutes of Health training grant (CA-09509).

Keywords

  • Antioxidant
  • CIP
  • Ciprofibrate
  • EMSA
  • FAO
  • IKK
  • IκB
  • IκB kinase
  • NF-κB
  • PPs
  • Peroxisome proliferators
  • Rats
  • Vitamin E
  • ciprofibrate
  • electrophoretic mobility shift assay
  • fatty acyl-CoA oxidase
  • inhibitor of κB
  • nuclear factor-kappa B

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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