Lipid accumulation in the livers of chlorpromazine-treated rats does not induce peroxisome proliferation.
Treatment of rats with 25 mg/kg/day of the neuroleptic drug chlorpromazine for periods of 7, 28 or 90 days causes a slow accumulation of lipid in large droplets in centrilobular hepatocytes. There is little or no damage to hepatocytes as assessed by changes in glucose-6-phosphatase activity and by electron microscopy. Furthermore there is no indication of a change in peroxisomal beta-oxidation of fatty acids or in microsomal omega-oxidation of fatty acids. It is, therefore, clear that lipid accumulation in the liver does not automatically induce peroxisomal and microsomal fatty acid oxidising enzymes.
Price
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Hinton
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D000818:Animals; D002374:Catalase / Q000378:metabolism; D002746:Chlorpromazine / Q000633:toxicity*; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005234:Fatty Liver / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D008830:Microbodies / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D002374:Catalase; D042926:Cytochrome P-450 CYP4A; C028427:palmitoyl CoA oxidase; D005952:Glucose-6-Phosphatase; D002746:Chlorpromazine