Peroxisomes and Hepatotoxicity |
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Authors: | N. Latruffe C. Pacot P. Passilly M. Petit O. Bardot F. Caira M. Cherkaoui Malki B. Jannin M. C. Clemencet P. Deslex |
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Affiliation: | (1) Laboratory of Molecular and Cellular Biology, University of Burgundy, Dijon Cedex, France;(2) Sanofi-Winthrop Recherche, Longvie-Dijon, France;(3) Laboratory of Molecular and Cellular Biology, University of Burgundy, BP 138, 21004 Dijon Cedex, France |
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Abstract: | Peroxisomes are ubiquitous organelles of eukaryotic cells and are present in significant amounts in hepatic liver cells. Peroxisomal enzymes contribute to several metabolic pathways including fatty acid, purine and amino acid catabolism or bile acid synthesis. The peroxisomal oxidative reactions produce hydrogen peroxide, mostly degraded by catalase which prevents oxidative stress. Moreover, peroxisomes are involved in arylderivative drug detoxification through its epoxide hydrolase activity.In rodents the exposure of cells to xenobiotic compounds such as fibrates, phthalates/adipates and chlorophenoxyacetic acid derivatives, which are used as hypolipaemic drugs, plasticizers and pesticides respectively, lead to a liver mass increase and to a high peroxisome proliferation. This latter event is due to a strong genetic activation triggered by the PPAR (peroxisome proliferator activated nuclear receptor).Human contrasts with rodent since there is no, or little, effect of the above cited compounds. In contrast, the defect of single or multiple peroxisomal functions caused by genetic disorders lead to an increase of very long chain fatty acid level, which is toxic, especially for brain and kidney. The liver response to xenobiotics of the peroxisome proliferator class may be modulated by auxiliary compounds such as hormones (e.g. thyroid hormone) or nutriments (e.g. retinoids).Originally presented at the Second European Comparative Clinical Pathology Conference, Dijon. |
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Keywords: | Cell lines Guinea pig Human Hypolipaemic agents Peroxisome proliferators Rat Species difference |
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