Role of vascular congestion in cisplatin-induced acute renal failure in the rat.
The significance of vascular congestion in the pathogenesis of cisplatin acute renal failure (ARF) was studied in rats given pentoxifylline. Rats were administered single intraperitoneal doses of 1.0, 2.5, 5.0, and 10.0 mg/kg of cisplatin with 45 mg/kg of pentoxifylline or saline every 12 h for 3 days. Cisplatin caused dose-dependent declines in the mean inulin clearance values in the rat that were not attenuated with pharmacological doses of pentoxifylline. There were no differences in histology, urinary electrolyte excretion rates, and serum creatinine values between cisplatin toxicity groups treated with saline or pentoxifylline. Erythrocyte congestion was studied with 51Cr-labelled erythrocytes in rats given single doses of 5 mg/kg of cisplatin with and without pentoxifylline in an attempt to define the role of capillary sludging. The papilla, medulla, and cortex of kidneys of cisplatin-treated rats were markedly congested with 51Cr-erythrocytes; however, pentoxifylline treatment did not significantly reduce the congestion. These data suggest that although erythrocyte trapping is involved in cisplatin ARF, treatment with pharmacological doses of vascular decongestants does not fully attenuate the functional defect.
Luke
D R
DR
Department of Pharmaceutics, University of Houston, Texas.
Vadiei
K
K
Lopez-Berestein
G
G
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000517:prevention & control; D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004912:Erythrocytes; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D010431:Pentoxifylline / Q000008:administration & dosage; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects
D002945:Cisplatin; D010431:Pentoxifylline