HISTOCHEMICAL EVIDENCE THAT PLASMA AND MITOCHONDRIAL-MEMBRANES ARE PRIMARY FOCI OF HEPATOCELLULAR INJURY CAUSED BY 1,1-DICHLOROETHYLENE

  • 1 January 1982
    • journal article
    • research article
    • Vol. 46  (4) , 413-421
Abstract
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 g male Sprague-Dawley rats were sacrificed 1, 2, 4 or 6 h after an oral dose of 200 mg 1,1-DCE/kg (in mineral oil) and 6 h after 50, 100 or 150 mg 1,1-DCE/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. Early injury (2 h following the 200 mg/kg dose) and slight injury (6 h following the 50 mg/kg dose) were characterized by increased liver Na levels and decreases in the central area staining patterns of bile canaliculi membrane Mg2+-ATPase and 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. Only at later times (4 and 6 h) 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. These later appearing alterations were secondary consequences of the midzonal necrosis and sinusoidal congestion produced by 1,1-DCE; the plasma membranes and mitochondrial membranes were the primary foci of injury.

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