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Journal of Zhejiang University SCIENCE A 2000 Vol.1 No.1 P.91-96

http://doi.org/10.1631/jzus.2000.0091


MITOCHONDRIAL DYSFUNCTION AT THE EARLY STAGE OF CISPLATIN-INDUCED ACUTE RENAL FAILURE IN RATS


Author(s):  XIE Li-ping, C.Skrezek, H. Wand, F.Reibe

Affiliation(s):  Dept.of Urology, First Affiliated Hospital, College of Medicine, Zhejiang University,Hangzhou 310003,China; more

Corresponding email(s): 

Key Words:  acute renal failure, cisplatin, pathogenesis, kidney tubule, mitochondria


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XIE Li-ping, C.Skrezek, H. Wand, F.Reibe. MITOCHONDRIAL DYSFUNCTION AT THE EARLY STAGE OF CISPLATIN-INDUCED ACUTE RENAL FAILURE IN RATS[J]. Journal of Zhejiang University Science A, 2000, 1(1): 91-96.

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Abstract: 
The present study was undertaken to clarify the pathogenesis of cisplatin-induced acute renal failure at the early stage. Male Sprague-Dawley rats were given an intravenous administration of 10 mg/kg cisplatin. 0.9% saline was infused into them at a rate of 2 ml/h for 3 h, starting with a 2-ml bolus injection before cisplatin administration. 3 h following cisplatin administration, no evident morphological abnormalities were found by both light and electron microscopy; there were also no significant changes in GFR. Thirty min after cisplatin injection, urine sodium and potassium excretion increased by 56% and 260% those of the control animals, respectively. Apparent renal mitochondrial respiration dysfunction was observed in cisplatin-treated rats 3 h later; the state 4 respiration increased by 100% and state 3 respiration, respiratory control ratio and carbonyl cyanide p-trifluoromethoxyphenyl hydrazone-uncoupled respiration decreased by 46%, 74% and 47% of the controls, respectively. The present data suggest that mitochondrial dysfunction may be a very early event in cisplatin-induced acute renal failure in rats.

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Reference

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[5]Jones, T. W., Chopra, S., Kaufman J. S. et al., 1985. Cis-diamminedichloroplatinum(II)-induced acute renal failure in the rat. Correlation of structural and functional alterations.Lab Invest 52:363.

[6]Laurent, G., Yernaux, V., Nonclercq, D. et al., 1988. Tissue injury and proliferative response induced in rat kidney by cis-diamminedichloroplatinum(II).Virchows Arch (Cell Pathol):55:129.

[7]Markwell, M. A. K., Haas, S. M.,Bieber, L. L. et al., 1978. A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples.Anal Biochem 87:206.

[8]Offerman, J. J. G.,Meijer, S.,Sleifer, D. Th. et al., 1984. Acute effects of cis-diamminedichloroplatinum (CDDP) on renal function.Cancer Chemother Pharmacol 12:36.

[9]Safirstein, R., Winston, J., Moel, D. et al., 1987. Cisplatin nephrotoxicity: insights into mechanism.Int J Androl 10:325.

[10]Silva, P., 1987. Renal fuel utilization, energy requirements, and function.Kidney Int 32:S9.

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