Liver endoplasmic reticulum: target site of halocarbon metabolites.
Initial injury produced by exposure of rats to carbon tetrachloride, halothane, vinyl chloride or trichlorethylene appears to involve the endoplasmic reticulum. First, there is dispersion of the ergastoplasm, then vacuolization and degranulation of the rough endoplasmic reticulum with concomitant retraction of the smooth endoplasmic reticulum into tightly clumped tubular aggregates. In addition, membranes in these tubular aggregates seem to undergo supra-molecular disassembly. Along with this structural disorganization, functional capacity of the organelle diminishes. Activation of these halocarbons to toxic species by functional elements of the endoplasmic reticulum is indicated by the enhancement of their toxicity by pretreatment with chemicals which induce components of the mixed function oxidase system and by the formation of certain metabolites and/or covalently bound products. Insight into the molecular mechanisms of membrane injury brought about by these halocarbon hepatotoxins has been provided by the characterization of chemical changes produced, such as increased lipid diene conjugate content, and the patterns of enzyme deactivation.
D000818:Animals; D002251:Carbon Tetrachloride / Q000378:metabolism / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury; D002725:Chloroform / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D005609:Free Radicals; D006846:Hydrocarbons, Halogenated / Q000494:pharmacology*; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D010545:Peroxides / Q000378:metabolism; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism; D014752:Vinyl Chloride / Q000494:pharmacology
D005609:Free Radicals; D006846:Hydrocarbons, Halogenated; D010545:Peroxides; D002725:Chloroform; D002251:Carbon Tetrachloride; D014752:Vinyl Chloride