Molecular Pharmacology, Vol 20, 685-693, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Correlations among the Changes in Hepatic Microsomal Components after Intoxication with Alkyl Halides and Other Hepatotoxins

¹ Department of Pathology, University of California School of Medicine, San Francisco, California 94143

Male rats were given a single dose of 1 of 13 alkyl halides [2 of which produced lipid peroxidation (carbon tetrachloride and bromotrichloromethane) and 11 of which did not (chloroform, bromoform, dichloromethane, dibromomethane, 1,2-dichloroethane, 1,2-dibromoethane, 1-bromo-2-chloroethane, 1,1,2-trichloroethane, 1,2,3-trichloropropane, 1,2-dibromo-3-chloropropane, and 1,2-epoxy-3-chloropropane] or 4 other hepatotoxins (dimethylnitrosamine, thioacetamide, ethionine, and cadmium acetate). Eighteen hours later, hepatic microsomes were isolated and their protein, RNA, phospholipid, cytochrome P-450, cytochrome b₅, NADPH cytochrome c reductase, and fatty acid contents were determined. The cytochrome P-450 content decreased significantly after 14 of the treatments, and cytochrome b₅ and NADPH cytochrome c reductase contents decreased significantly after five and four of the treatments, respectively. The majority of the treatments resulted in a shift of the microsomal fatty acid content, characterized by increases in the relative contents of linoleic (12 treatments), palmitic (11 treatments), and oleic acids (9 treatments), and decreases in the relative contents of arachidonic (14 treatments) and stearic acids (9 treatments). The decreases in cytochromes P-450 and b₅ showed high degrees of correlation with the decrease in arachidonic acid (r = 0.90 and 0.86, respectively) and the increase in linoleic acid (r = -0.80 and -0.65, respectively). These strong correlations were also found when values for the rats given the four hepatotoxins were considered alone. However, slightly lower correlations were determined when the data for the four other hepatotoxins and/or the data for the lipid peroxidation-positive alkyl halides were omitted from the calculations. The possible relationship between changes in microsomal cytochromes and polyunsaturated fatty acids is discussed.

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