Pathological mechanisms in carbon tetrachloride hepatotoxicity.
Liver cell injury induced by carbon tetrachloride involves initially the metabolism of carbon tetrachloride to trichloromethyl free-radical by the mixed function oxidase system of the endoplasmic reticulum. It is postulated that secondary mechanisms link carbon tetrachloride metabolism to the widespread disturbances in hepatocyte function. These secondary mechanisms could involve the generation of toxic products arising directly from carbon tetrachloride metabolism or from peroxidative degeneration of membrane lipids. The possible involvement of radical species such as trichloromethyl (.CCl3), trichloromethylperoxy (.OOCCl3), and chlorine (.Cl) free radicals, as well as phosgene and aldehydic products of lipid peroxidation, as toxic intermediates is discussed. Data do not support the view that an increase in cytosolic free calcium is important in the toxic action of carbon tetrachloride or bromotrichloromethane. In addition, carbon tetrachloride-induced inhibition of very low density lipoprotein secretion by hepatocytes is not a result of elevated levels of cytosolic free calcium.
D000818:Animals; D001975:Bromotrichloromethane / Q000633:toxicity; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000378:metabolism / Q000633:toxicity*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D003593:Cytoplasm / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004789:Enzyme Activation; D005609:Free Radicals; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D010705:Phosgene / Q000378:metabolism; D010741:Phospholipases A / Q000032:analysis; D010738:Type C Phospholipases / Q000032:analysis
D005609:Free Radicals; D008054:Lipid Peroxides; D008079:Lipoproteins, VLDL; D010705:Phosgene; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride; D010741:Phospholipases A; D010738:Type C Phospholipases; D001975:Bromotrichloromethane; D002118:Calcium