Effect of copper deficiency and cis-diamminedichloroplatinum (II) treatment on the activities of renal microvillar enzymes in rats.
Recent studies have shown that some manifestations of cis-diamminedichloroplatinum (II) (cis-Pt) induced nephrotoxicity in animals may be exacerbated if the animals are nutritionally deprived of copper. The objective of the present study was to determine the effects of cis-Pt induced toxicity on enzyme activities in the kidney microvilli of rats with different copper statuses. Weanling male rats were fed copper-deficient (CuD) (less than 1 mg/kg Cu of diet) or copper-adequate (CuA) (5 mg/L of Cu in drinking water) regimens. After 24 days, rats were given i.v. injections of either cis-Pt (5 mg/kg BW) or saline in a 2 x 2 factorial design. At days 2 and 4 post-injection rats were killed and tubular microvilli isolated from the kidney cortex. Each preparation was assayed for the activities of 5 membrane-bound enzymes. Angiotensin-I converting enzyme (ACE) activity was 20 to 30% higher in the microvilli of CuD rats than in controls. Cis-Pt treatment enhanced ACE activity as well, and activity in treated rats was 60 to 110% higher than in controls. At day 2 there was a 20% greater increase in ACE activity in cis-Pt-treated CuD rats than in CuA rats. Aminopeptidase N activity was 35% lower in CuD rats than controls, but activity was not affected by cis-Pt. Gamma-glutamyltransferase activity was lowered by as much as 30% in cis-Pt-treated rats when compared to controls, but there was no effect of copper deficiency. Alkaline phosphatase and neutral endopeptidase 24.11 activities were significantly lower in microvilli of cis-Pt-treated rats than in those not treated.(ABSTRACT TRUNCATED AT 250 WORDS)
Reeves
P G
PG
United States Department of Agriculture, Grand Forks Human Nutrition Research Center, ND 58202.
Noordewier
B
B
Saari
J T
JT
D000469:Alkaline Phosphatase / Q000378:metabolism; D000626:Aminopeptidases / Q000378:metabolism; D000818:Animals; D001806:Blood Urea Nitrogen; D018826:CD13 Antigens; D002462:Cell Membrane / Q000201:enzymology; D002945:Cisplatin / Q000627:therapeutic use* / Q000633:toxicity; D003300:Copper / Q000172:deficiency* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000737:chemistry; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015260:Neprilysin / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015032:Zinc / Q000032:analysis; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D003300:Copper; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase; D000626:Aminopeptidases; D018826:CD13 Antigens; D007703:Peptidyl-Dipeptidase A; D015260:Neprilysin; D015032:Zinc; D002945:Cisplatin