Response of genetically obese Zucker rats to ciprofibrate,a hypolipidemic agent,with peroxisome proliferation activity as compared to Zucker lean and Sprague-Dawley rats |
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Authors: | Corinne Pacot Michel Petit Franoise Caira Michel Rollin Niloufar Behechti Stphane Grgoire Mustapha Cherkaoui Malki Chantal Cavatz Maryvonne Moisant Christine Moreau Corinne Thomas Grard Descotes Jean-Franois Gallas Paul Deslex Jürgen Althoff Jean-Pierre Zahnd Jean-Claude Lhuguenot Norbert Latruffe |
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Institution: | Corinne Pacot,Michel Petit,Françoise Caira,Michel Rollin,Niloufar Behechti,Stéphane Grégoire,Mustapha Cherkaoui Malki,Chantal Cavatz,Maryvonne Moisant,Christine Moreau,Corinne Thomas,Gérard Descotes,Jean-François Gallas,Paul Deslex,Jürgen Althoff,Jean-Pierre Zahnd,Jean-Claude Lhuguenot,Norbert Latruffe |
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Abstract: | 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. |
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Keywords: | ciprofibrate Zucker rats peroxisomes enzyme induction liver |
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