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Effects of the PPARα Agonist and Widely Used Antihyperlipidemic Drug Gemfibrozil on Hepatic Toxicity and Lipid Metabolism
Joint Authors
Stout, Matthew D.
Travlos, Gregory S.
Herbert, Ronald A.
Hejtmancik, Milton R.
Cunningham, Michael L.
Collins, Bradley J.
Vallant, Molly K.
Source
Issue
Vol. 2010, Issue 2010 (31 Dec. 2010), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2010-10-04
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Natural & Life Sciences (Multidisciplinary)
Biology
Abstract EN
Gemfibrozil is a widely prescribed hypolipidemic agent in humans and a peroxisome proliferator and liver carcinogen in rats.
Three-month feed studies of gemfibrozil were conducted by the National Toxicology Program (NTP) in male Harlan Sprague-Dawley rats, B6C3F1 mice, and Syrian hamsters, primarily to examine mechanisms of hepatocarcinogenicity.
There was morphologic evidence of peroxisome proliferation in rats and mice.
Increased hepatocyte proliferation was observed in rats, primarily at the earliest time point.
Increases in peroxisomal enzyme activities were greatest in rats, intermediate in mice, and least in hamsters.
These studies demonstrate that rats are most responsive while hamsters are least responsive.
These events are causally related to hepatotoxicity and hepatocarcinogenicity of gemfibrozil in rodents via peroxisome proliferator activated receptor-α (PPARα) activation; however, there is widespread evidence that activation of PPARα in humans results in expression of genes involved in lipid metabolism, but not in hepatocellular proliferation.
American Psychological Association (APA)
Cunningham, Michael L.& Collins, Bradley J.& Hejtmancik, Milton R.& Herbert, Ronald A.& Travlos, Gregory S.& Vallant, Molly K.…[et al.]. 2010. Effects of the PPARα Agonist and Widely Used Antihyperlipidemic Drug Gemfibrozil on Hepatic Toxicity and Lipid Metabolism. PPAR Research،Vol. 2010, no. 2010, pp.1-14.
https://search.emarefa.net/detail/BIM-490120
Modern Language Association (MLA)
Cunningham, Michael L.…[et al.]. Effects of the PPARα Agonist and Widely Used Antihyperlipidemic Drug Gemfibrozil on Hepatic Toxicity and Lipid Metabolism. PPAR Research No. 2010 (2010), pp.1-14.
https://search.emarefa.net/detail/BIM-490120
American Medical Association (AMA)
Cunningham, Michael L.& Collins, Bradley J.& Hejtmancik, Milton R.& Herbert, Ronald A.& Travlos, Gregory S.& Vallant, Molly K.…[et al.]. Effects of the PPARα Agonist and Widely Used Antihyperlipidemic Drug Gemfibrozil on Hepatic Toxicity and Lipid Metabolism. PPAR Research. 2010. Vol. 2010, no. 2010, pp.1-14.
https://search.emarefa.net/detail/BIM-490120
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-490120