Effect of cisplatin on renal function in rabbits: mechanism of reduced glucose reabsorption.
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 (Uosm), free-water reabsorption, (TcH2O), and urine to plasma creatinine ratio (U/Pcr). 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.
Kim
Y K
YK
Department of Physiology, College of Medicine, Pusan National University, Korea.
Byun
H S
HS
Kim
Y H
YH
Woo
J S
JS
Lee
S H
SH
D000596:Amino Acids / Q000652:urine; D000818:Animals; D001806:Blood Urea Nitrogen; D002462:Cell Membrane / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D005919:Glomerular Filtration Rate / Q000187:drug effects; D018698:Glutamic Acid / Q000652:urine; D006029:Glycosuria / Q000139:chemically induced; D007274:Injections, Intraperitoneal; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D008854:Microscopy, Electron; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D009994:Osmolar Concentration; D010042:Ouabain / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010710:Phosphates / Q000652:urine; D011188:Potassium / Q000652:urine; D011817:Rabbits; D012964:Sodium / Q000652:urine; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism
D000596:Amino Acids; D009004:Monosaccharide Transport Proteins; D010710:Phosphates; D018698:Glutamic Acid; D010042:Ouabain; D012964:Sodium; D003404:Creatinine; D000254:Sodium-Potassium-Exchanging ATPase; D002945:Cisplatin; D011188:Potassium