Biochemical alterations in livers of rats exposed to vinyl chloride

Abstract

Sprague‐Dawley rats were exposed to vinyl chloride to determine the earliest sequential biochemical changes occurring with liver injury before angiosarcoma development. Activity of glucose‐6‐phosphatase, a key gluconeogenic enzyme in the liver microsomal fraction, decreased 25% with respect to controls after 70 h of exposure. Glucose‐6‐phosphate dehydrogenase activity increased twofold after more than 100 h of exposure. Nonprotein sulfhydryl levels (glutathione and/or cysteine) showed a slight but progressive elevation, whereas glutathione reductase activity increased 50–60% during exposure to vinyl chloride. NADPH‐cytochrome c reductase and mixed function oxidase were unchanged in the same microsomal fraction. There were no changes in seven conventional clinical biochemical liver tests or in four other markers of liver mitochondrial, cytosol, and microsomal function. No significant histological changes were found on light microscopic examination during this exposure period. However, with electron microscopy, dilation of rough endoplasmic reticulum was seen in the animals exposed for more than 137 h. These enzymatic changes are considered to reflect early hepatocellular adaptation to vinyl chloride exposure with very mild or limited hepatocellular injury in its earliest stage.