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Hepatocellular biomembrane peroxidation in copper-induced injury
xiii, 159 leaves : illustrations ; 29 cm
The pathogenesis of copper-induced hepatocellular biomembrane peroxidation was studied in male Fischer rats by analyzing hepatic morphologic alterations, measuring the activity of hepatic free radical scavenger enzymes, and determining the distribution of hepatic cytosolic copper bound to high and low molecular weight proteins. Seventy-five weanling rats were divided into 3 groups of 25 each and injected once daily with either 6.25 mg/kg or 12.5 mg/kg cupric chloride, or 0.2 ml/100 gm saline. Five rats from each group were killed after 3, 14, 28, 42, and 70 consecutive days of injections. The level of malondialdehyde was elevated after 3 days of copper injections and continued to increase until it peaked in the high-dose group after 28 days and in the low-dose group after 42 days. There was good correlation between the concentration of total copper and the level of malondialdehyde. The density of catalase-containing peroxisomes was reduced in copper-treated rats, correlating with a reduced activity of hepatic catalase. Catalase activity in copper-treated rats was reduced after 3 days, and always remained less than or equal to the activity in control rats. The activity of glutathione peroxidase in high-dose rats always was less than or equal to the level in control rats, while the activity in control rats always was less than or equal to the level in low-dose rats. Meanwhile, the activity of superoxide dismutase increased in copper-treated rats after 28 days. Thus, the rather complex pathogenesis of copper-induced hepatocellular biomembrane peroxidation included the selective inhibition of certain free radical scavenger enzymes. The concentration of cytosolic low molecular weight protein-bound copper was elevated after 3 days in both copper-treated groups and continued to increase, leveling off or peaking after 42 days. Regression analysis and in vitro studies, involving the peroxidation of erythrocyte ghost membranes, demonstrated that copper bound to low molecular weight proteins was less likely to induce lipoperoxidation than copper bound to high molecular weight proteins. There was good correlation between the accumulation of stainable copper-associated protein and the concentration of low molecular weight protein-bound copper supporting the contention that copper-associated protein is a low molecular weight copper-binding protein.
Includes bibliographical references (leaves 132-146).