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Title: Hepatocellular biomembrane peroxidation in copper-induced injury

Thesis/Dissertation ·
OSTI ID:6753977

The pathogenesis of Cu-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 Cu bound to high and low molecular weight proteins. Seventy-five weanling rats were divided into 3 group 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 Cu 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. The density of catalase-containing peroxisomes was reduced in Cu-treated rats, correlating with a reduced activity of hepatic catalase. Catalase activity in Cu-treated rats was reduced after 3 days, and always remained < or = to the activity in control rats. The activity of glutathione peroxidase in high-dose rats always was < or = to the level in control rats, while the activity in control rats always was < or = to the level in low-dose rats. Meanwhile, the activity of superoxide dismutase increase in Cu-treated rats after 28 days. The concentration of cytosolic low molecular weight protein-bound Cu was elevated after 3 days in both Cu-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 Cu bound to low molecular weight proteins was less likely to induce lipoperoxidation than copper bound to high molecular weight proteins.

Research Organization:
Texas A and M Univ., College Station (USA)
OSTI ID:
6753977
Resource Relation:
Other Information: Thesis (Ph. D.)
Country of Publication:
United States
Language:
English