Lipid peroxidation and alteration of membrane lipids in isolated hepatocytes exposed to carbon tetrachloride.
Lipid peroxidation, determined by malondialdehyde formation, occurs at a low, but detectable, rate in parenchymal cells isolated from livers of fasted rats. Pretreatment of rats with phenobarbital increased malondialdehyde formation about 2-fold, probably because of the increased amount of endoplasmic reticulum. Lipid peroxidation was increased in the cells by the addition of either NADPH or CCl4, and the effect of the two agents together was more than additive. Phenobarbital pretreatment increased peroxidation due to exposure of the cells to CCl4 but not that associated with NADPH addition. The amount of CCl4 producing a 50% increase in malondialdehyde formation was about 3-fold less for cells from phenobarbital-treated rats than for those from control rats. Decreased cytochrome P450 levels in isolated hepatocytes produced by prior treatment of rats with allylisopropylacetamide enhanced lipid peroxidation from endogenous substrates but did not affect lipid peroxidation caused by the addition of NADPH. Allylisopropylacetamide markedly lowered lipid peroxidation caused by CCl4 in proportion to the loss of cytochrome P450. Malondialdehyde production associated with metabolism of endogenous substrates in the cells, or resulting from incubation of the cells with NADPH was not accompanied by changes in the fatty acid or protein content of three membranous fractions (microsomal mitochondrial, and cell debris) isolated from homogenates of these cells. Exposure of liver cells to CCl4, however, caused major losses in all fatty acids and of protein from the microsomal fraction, but only polyunsaturated fatty acids were decreased in the cellular debris fraction. Incubation with NADPH and CCl4 together enhanced malondialdehyde formation, but caused no further decrease in fatty acid content in these two fractions. Mitochondrial fatty acids were not decreased by any treatments described.
D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D050356:Lipid Metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010545:Peroxides / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats
D010545:Peroxides; D008315:Malondialdehyde; D002251:Carbon Tetrachloride; D010634:Phenobarbital