Effect of excess and deficient copper intake on hepatic microsomal metabolism and toxicity of foreign chemicals.
Moffitt-R Jr.; Murphy-SD
Trace Substances in Environmental Health - VII: Proceedings of the University of Missouri's 7th Annual Conference on Trace Substances in Environmental Health, June 12-14, 1973, University of Missouri - Columbia, Columbia Missouri. Hemphill DD, ed., Columbia, MO: University of Missouri, 1974 Jan; :213-223
Effects of excess and deficient copper (7440508) (Cu) intake on hepatic microsomal metabolism were investigated in male Holtzmann- rats. Rats were given drinking water containing 50, 150, or 450 parts per million (ppm) Cu for 30 days or were fed a Cu deficient diet for 3 or 6 weeks. Animals were given oral doses of 0.25 and 2.5 milliliters per kilogram carbon-tetrachloride (56235) or 1.5 milligrams per kilogram parathion (56382) by intraperitoneal injection. Drug metabolism was measured. Animals were sacrificed and tissue homogenates were prepared. Hepatic microsomal activities were measured, hepatic lipid peroxidation was determined, and blood was assayed for methemoglobin. Liver metal concentrations and enzymatic cleavage of parathion were determined. In rats given supplemented diets, liver Cu concentrations increased with increasing dose. Aniline hydroxylase activity was reduced by 80 percent at 450ppm Cu. Growth retardation was seen in rats given deficient diets, but no effects on liver/body weight ratios or liver proteins were seen. There was a significant reduction in hepatic microsomal metabolism of aniline after 3 or 6 weeks on deficient diets. Hepatic benzpyrene hydroxylase activity was slightly increased and microsomal metabolism or hexobarbital was reduced by 70 percent after 6 weeks on the deficient diet; hexobarbital sleeping time was increased. The acute toxicity of parathion was markedly potentiated in rats deficient in Cu; Cu loading did not affect the toxicity of parathion. Carbon-tetrachloride produced dose dependent liver injury in all groups. Zoxazolamine paralysis time was increased in Cu deficient rats. The authors conclude that Cu imbalance can influence the rates of metabolism of foreign chemicals and may also alter the susceptibility of animals to their toxic and pharmacologic effects.
NIOSH-Grant; Animal-studies; Biological-effects; Light-metals; Metabolic-study; Solvents; Pesticides; Histochemical-analysis; Enzyme-activity; Toxicology
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Trace Substances in Environmental Health - VII: Proceedings of the University of Missouri's 7th Annual Conference on Trace Substances in Environmental Health, June 12-14, 1973, University of Missouri - Columbia, Columbia Missouri
Harvard University, Boston, Massachusetts