Effect of Cisplatin on Renal-Function in Rabbits: Mechanism of Reduced Glucose Reabsorption

doi:10.1006/taap.1995.1003

Toxicology and Applied Pharmacology

Volume 130, Issue 1, January 1995, Pages 19-26

https://doi.org/10.1006/taap.1995.1003 Get rights and content

Abstract

This study was performed to determine the effect of cisplatin (cis-diamminedichloroplatinum II) on renal function in rabbits. Injection of a single i.p. dose of 4 mg/kg cisplatin caused an increase in fractional excretion of Na⁺ and K⁺ and a decrease in urine osmolality (U_osm), free-water reabsorption, (T^cH₂O), and urine to plasma creatinine ratio (U/P_cr). Urine flow was decreased following cisplatin treatment, which was accompanied by marked reduction in GFR. Cisplatin induced glucosuria, phosphaturia, and aminoaciduria. These results suggest that cisplatin results in impaired proximal tubular reabsorptive function and the renal concentrating defect. Cisplatin treatment impaired the accumulation of PAH and TEA and ouabain-sensitive oxygen consumption in renal cortical slices. Na⁺-K⁺-ATPase activity in renal cortical microsomes and basolateral membrane vesicles was significantly depressed in cisplatin-treated animals. Cisplatin treatment did not affect the Na⁺-dependent uptake of glucose and L-glutamate by brush-border membrane vesicles (BBMV), but caused a significant decrease in Na⁺-dependent succinate and H⁺-dependent TEA uptake. Morphological observations showed that cisplatin caused a focal loss of the microvillus brush border. These results suggest that (1) cisplatin induces oliguric acute renal failure in rabbits and (2) glucosuria induced by cisplatin was not due to a direct impairment of glucose transporter in brush-border membranes but due to an inhibition of Na⁺-pump activity and a decrease in area for active glucose reabsorption in the proximal tubule.

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Citation Excerpt :
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Regular ArticleEffect of Cisplatin on Renal-Function in Rabbits: Mechanism of Reduced Glucose Reabsorption

Abstract

Regular Article
Effect of Cisplatin on Renal-Function in Rabbits: Mechanism of Reduced Glucose Reabsorption