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Peroxisome proliferator‐activated receptor‐β/δ protects against chemically induced liver toxicity in mice
Author(s) -
Shan Weiwei,
Nicol Christopher J.,
Ito Shinji,
Bility Moses T.,
Kennett Mary J.,
Ward Jerrold M.,
Gonzalez Frank J.,
Peters Jeffrey M.
Publication year - 2008
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21925
Subject(s) - endocrinology , medicine , toxicity , azoxymethane , peroxisome proliferator activated receptor delta , chemistry , biology , nuclear receptor , receptor , biochemistry , carcinogenesis , transcription factor , gene
Potential functional roles for the peroxisome proliferator‐activated receptor‐β/δ (PPARβ/δ) in skeletal muscle fatty acid catabolism and epithelial carcinogenesis have recently been described. Whereas PPARβ/δ is expressed in liver, its function in this tissue is less clear. To determine the role of PPARβ/δ in chemically induced liver toxicity, wild‐type and PPARβ/δ‐null mice were treated with azoxymethane (AOM) and markers of liver toxicity examined. Bile duct hyperplasia, regenerative hyperplasia, and increased serum alanine aminotransferase (ALT) were found in AOM‐treated PPARβ/δ‐null mice, and these effects were not observed in similarly treated wild‐type mice. Exacerbated carbon tetrachloride (CCl 4 ) hepatoxicity was also observed in PPARβ/δ‐null as compared with wild‐type mice. No differences in messenger RNAs (mRNAs) encoding cytochrome2E1 required for the metabolic activation of AOM and CCl 4 were observed between wild‐type or PPARβ/δ‐null mice in response to CCl 4 . Significant differences in the expression of genes reflecting enhanced nuclear factor kappa B (NF‐κB) activity were noted in PPARβ/δ‐null mice. Conclusion: Results from these studies show that PPARβ/δ is protective against liver toxicity induced by AOM and CCl 4 , suggesting that this receptor is hepatoprotective against environmental chemicals that are metabolized in this tissue. (H EPATOLOGY 2007.)