Histochemical evidence that plasma and mitochondrial membranes are primary foci of hepatocellular injury caused by 1,1-dichloroethylene.
Functional integrity of liver cell organelles in rats given the model abrupt cytotoxin 1,1-dichloroethylene (1,1-DCE) was examined by enzymatic histochemistry. Fasted 200-gm. male Sprague-Dawley rats were sacrificed 1, 2, 4, or 6 hours after an oral dose of 200 mg. of 1,1-DCE per kg. (in mineral oil) and 6 hours after 50, 100, or 150 mg. of 1,1-DCE per kg. Cubes of liver were quick frozen for histochemistry. Stage or degree of liver injury was assessed by histology and by measuring serum transaminase activities and liver ion levels. We found both early injury (2 hours following the 200-mg. per kg. dose) and slight injury (6 hours following the 50-mg. per kg. dose) characterized by: increases in liver sodium levels and striking decreases in the central area staining patterns of bile canaliculi membrane Mg++-ATPase, as well as of outer mitochondrial membrane monoamine oxidase and inner mitochondrial membrane succinate dehydrogenase and cytochrome oxidase. As injury progressed with time or increased in severity with dose, aberrations in the levels of other liver cell ions occurred, serum transaminase activities rose, and decreased staining of plasma membrane and mitochondrial membrane components were evident in progressively wider areas around the central vein. Glutathione depletion was panlobular. In contrast, only at later times (4 and 6 hours) and after the larger doses did alterations to functional components of the mitochondrial matrix, endoplasmic reticulum, lysosomes, and cytosol become evident in a narrow area around the central vein, which became necrotic. We consider these later appearing alterations secondary consequences of the midzonal necrosis and sinusoidal congestion produced by 1,1-DCE, whereas the plasma membranes and mitochondrial membranes appear to be primary foci of injury.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004000:Dichloroethylenes / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D006651:Histocytochemistry; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D007425:Intracellular Membranes / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D051381:Rats; D013997:Time Factors
D004000:Dichloroethylenes; D006843:Hydrocarbons, Chlorinated; D000251:Adenosine Triphosphatases