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Peroxisome Proliferator-Activated Receptor-/ Protects Against Chemically Induced Liver Toxicity in Mice

Summary: Peroxisome Proliferator-Activated Receptor- / Protects
Against Chemically Induced Liver Toxicity in Mice
Weiwei Shan,1,2 Christopher J. Nicol,4 Shinji Ito,4 Moses T. Bility,1,3 Mary J. Kennett,1 Jerrold M. Ward,5
Frank J. Gonzalez,4 and Jeffrey M. Peters1-3
Potential functional roles for the peroxisome proliferator-activated receptor- /
(PPAR / ) in skeletal muscle fatty acid catabolism and epithelial carcinogenesis have re-
cently been described. Whereas PPAR / is expressed in liver, its function in this tissue is
less clear. To determine the role of PPAR / in chemically induced liver toxicity, wild-type
and PPAR / -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 PPAR / -null mice, and these
effects were not observed in similarly treated wild-type mice. Exacerbated carbon tetrachlo-
ride (CCl4) hepatoxicity was also observed in PPAR / -null as compared with wild-type
mice. No differences in messenger RNAs (mRNAs) encoding cytochrome2E1 required for
the metabolic activation of AOM and CCl4 were observed between wild-type or PPAR / -
null mice in response to CCl4. Significant differences in the expression of genes reflecting
enhanced nuclear factor kappa B (NF- B) activity were noted in PPAR / -null mice.
Conclusion: Results from these studies show that PPAR / is protective against liver toxicity
induced by AOM and CCl4, suggesting that this receptor is hepatoprotective against envi-
ronmental chemicals that are metabolized in this tissue. (HEPATOLOGY 2008;47:225-235.)


Source: Andrews, Anne M. - Huck Institutes of the Life Sciences, Pennsylvania State University


Collections: Biology and Medicine