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 (U osm), free-water reabso...
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Published in | Toxicology and applied pharmacology Vol. 130; no. 1; pp. 19 - 26 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
San Diego, CA
Elsevier Inc
1995
Elsevier |
Subjects | |
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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
cH
2O), 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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AbstractList | 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
cH
2O), 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. 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. |
Author | Woo, J.S. Lee, S.H. Kim, Y.K. Byun, H.S. Kim, Y.H. |
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Keywords | Antineoplastic agent Renal function Toxicity Single dose Rabbit Ion transport Lagomorpha Glutamate Microsome Kidney Vertebrata Mammalia Animal Renal failure Mechanism of action |
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Snippet | 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... 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... |
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SubjectTerms | Amino Acids - urine Animals Biological and medical sciences Blood Urea Nitrogen Cell Membrane - drug effects Cisplatin - administration & dosage Cisplatin - toxicity Creatinine - blood Drug toxicity and drugs side effects treatment Glomerular Filtration Rate - drug effects Glutamic Acid - urine Glycosuria - chemically induced Injections, Intraperitoneal Kidney Cortex - drug effects Kidney Cortex - metabolism Kidney Tubules, Proximal - drug effects Kidney Tubules, Proximal - metabolism Medical sciences Microscopy, Electron Microsomes - drug effects Microsomes - enzymology Microvilli - drug effects Microvilli - metabolism Monosaccharide Transport Proteins - drug effects Monosaccharide Transport Proteins - metabolism Osmolar Concentration Ouabain - pharmacology Oxygen Consumption - drug effects Pharmacology. Drug treatments Phosphates - urine Potassium - urine Rabbits Sodium - urine Sodium-Potassium-Exchanging ATPase - drug effects Sodium-Potassium-Exchanging ATPase - metabolism Toxicity: urogenital system |
Title | Effect of Cisplatin on Renal-Function in Rabbits: Mechanism of Reduced Glucose Reabsorption |
URI | https://dx.doi.org/10.1006/taap.1995.1003 https://www.ncbi.nlm.nih.gov/pubmed/7839366 |
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