Possible role of endogenous toxigenic lipids in the carbon tetrachloride poisoned hepatocyte.
Work reviewed in this paper indicates the potential importance of endogenous toxigenic lipids in amplifying the pathological consequences of lipid peroxidation in CCl4 poisoning. Formation of trichloromethane free radicals and the mixed function oxidase locus in the smooth endoplasmic reticulum of the hepatocyte and subsequent initiation of lipid peroxidation at this site are the first of a complex series of events that lead to the expression of CCl4 toxicity. Since lipid peroxidation is highly focal, it has been proposed that toxic products of lipid peroxidation could be released from the endoplasmic reticulum and that such substances might be responsible for the proliferation of intracellular damage. At least two classes of toxigenic substances are generated by microsomes undergoing NADPH-dependent lipid peroxidation. One group is a mixture of phospholipids of about 750 daltons to which are attached peroxidized fatty acids. A second group is a collection of low-molecular-weight compounds, which are decomposition products of peroxidized fatty acids. Both groups may act as intracellular toxigenic agents. Furthermore, fatty acids cleaved from peroxidized membrane phospholipids possess pharmacological activity resembling the activity of prostaglandins and these compounds also may contribute to cellular injury.
D001711:Biotransformation; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury; D005609:Free Radicals; D008563:Membrane Lipids / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D010545:Peroxides
D005609:Free Radicals; D008563:Membrane Lipids; D010545:Peroxides; D009249:NADP