Chlordecone-induced hepatic dysfunction.
Chlordecone (Kepone) is a decachloroketone analog of the dodecachlorohydrocarbon mirex and is used as a stomach poison insecticide. Despite the structural similarity to mirex, chlordecone is unlike mirex in general organ-specific toxic properties. Chlordecone is primarily accumulated in the liver, where it causes a variety of morphological and biochemical alterations. Although less effective than mirex as a hepatotoxin, it causes liver enlargement, focal necrosis, mitochondrial changes, fatty infiltration of hepatocytes, and proliferation of endoplasmic reticulum. Chlordecone accumulation and morphological alterations in the liver were also observed in occupationally exposed human patients. Induction of hepatic microsomal mixed-function oxidases (MFOs) and impaired production and utilization of hepatocellular energy are the principal biochemical aberrations produced by chlordecone. Chronic exposure causes carcinogenesis in mice and rats. Hyperplastic nodules, which progress to hepatocellular carcinomas, are the principal pathological lesions. Acute and chronic exposures to chlordecone result in hepatobiliary dysfunction manifested as impaired excretion of anionic compounds accompanied by choleresis. Exposure to chlordecone results of greatly potentiated haloalkane hepatotoxicity, representing a most potent toxic interaction at otherwise individually nontoxic levels. In view of the demonstrated carcinogenic effect of chlordecone, such interactions at very low levels assume extraordinary significance in terms of chronic toxicological and pathological manifestations induced by combinations of toxic chemicals.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D001646:Bile / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury; D007631:Chlordecone / Q000378:metabolism / Q000633:toxicity*; D002725:Chloroform / Q000633:toxicity; D004357:Drug Synergism; D004734:Energy Metabolism / Q000187:drug effects; D004790:Enzyme Induction; D005260:Female; D007306:Insecticides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced; D008297:Male; D051379:Mice; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D051381:Rats
D007306:Insecticides; D002725:Chloroform; D002251:Carbon Tetrachloride; D006899:Mixed Function Oxygenases; D000251:Adenosine Triphosphatases; D007631:Chlordecone