Effect of copper deficiency and cis-diamminedichloroplatinum (II) treatment on the activities of renal microvillar enzymes in rats
Reeves, P.G.; Noordewier, B.; Saari, J.T.
Journal of Trace Elements and Electrolytes in Health and Disease 4(1): 11-19
1990
ISSN/ISBN: 0931-2838 PMID: 1983771 Document Number: 367016
Previous studies have shown that some symptoms of cis-diamminedichloroplatinum (II) (cis-Pt) induced nephrotoxicity in animals may be exacerbated if the animals are nutritionally deprived of copper. Weanling male rats were fed a copper-deficient diet (CuD) (<1 mg Cu per kg diet) or given adequate copper (CuA) via the drinking water (5 mg Cu per litre). After 24 days, rats were given injections of cis-Pt (5 mg/kg body weight) or saline in a 2 x 2 factorial design. 2 and 4 days after injection rats were killed, tubular microvilli isolated from the kidney cortex, and the activities of 5 membrane-bound enzymes were measured. Angiotensin-I converting enzyme (ACE) activity was 20-30% higher in the microvilli of CuD rats than in CuA rats. Cis-Pt treatment increased ACE activity, and activity in treated rats was 60-110% higher than in untreated rats. At day 2, cis-Pt caused a 20% greater increase in ACE activity in CuD rats than in CuA rats. Aminopeptidase N activity was 35% lower in CuD rats than in control rats, but activity was not affected by cis-Pt. gamma -Glutamyltransferase activity was lowered by as much as 30% in treated rats compared with untreated rats, but there was no effect of copper intake. Alkaline phosphatase and neutral endopeptidase activities were significantly lower in treated rats than in untreated rats. Copper intake had no effect on the activities of these 2 enzymes. The concentration of zinc was higher in kidneys of treated rats than in kidneys of untreated rats. Cis-Pt also increased zinc in the liver, but only in CuD rats. It is concluded that some of the toxic effects of cis-Pt were increased by poor copper status.