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Response of genetically obese Zucker rats to ciprofibrate, a hypolipidemic agent, with peroxisome proliferation activity as compared to Zucker lean and Sprague‐Dawley rats
Author(s) -
Pacot Corinne,
Petit Michel,
Caira Françoise,
Rollin Michel,
Behechti Niloufar,
Grégoire Stéphane,
Malki Mustapha Cherkaoui,
Cavatz Chantal,
Moisant Maryvonne,
Moreau Christine,
Thomas Corinne,
Descotes Gérard,
Gallas JeanFrançois,
Deslex Paul,
Althoff Jürgen,
Zahnd JeanPierre,
Lhuguenot JeanClaude,
Latruffe Norbert
Publication year - 1993
Publication title -
biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 85
eISSN - 1768-322X
pISSN - 0248-4900
DOI - 10.1016/s0248-4900(05)80171-6
Subject(s) - endocrinology , medicine , peroxisome , catalase , biology , phenotype , cytochrome p450 , clofibrate , inbred strain , pharmacology , receptor , metabolism , biochemistry , oxidative stress , gene
Summary— Genetically obese Zucker (fa/fa) rats were used as an experimental model to study the effects of hypolipidemic agents on peroxisome proliferation; comparison was made with Zucker lean phenotype (Fa/−) and Sprague‐Dawley strain/phenotype. The pharmacokinetics of a single administration of ciprofibrate (1 or 3 mg/kg), appeared to be similar in all strains/phenotypes. After a 2‐week oral administration at the same dosages, there were dosage‐related increases in hepatocellular peroxisomal yield and in the hepatic enzymes' cyanide‐insensitive acyl‐CoA oxidase and catalase. The peroxisomal yield was less increased in Zucker than in Sprague‐Dawley rats, while the enzyme activities were similarly increased. Although the absolute specific activity of microsomal ω‐lauryl hydroxylase (cytochrome P4504A1) was lower in Zucker rats, it was increased more in this strain than in Sprague‐Dawley rats in response to drug exposure. The hypolipidemic effect (cholesterol and triglyceride reduction) was more pronounced in Zucker obese rats. Based on biochemical and morphological results, no major differences between strains/phenotypes in terms of peroxisome proliferation were observed following a 2‐week administration of ciprofibrate.