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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.

[1]Brady, H. R.,Kone, B. C.,Stromski, M. E. et al., 1990. Mitochondrial injury:an early event in cisplatin toxicity to renal proximal tubules.Am J Physiol 258:F1181.

[2]Chopra, S., Kaufman, J. S., Jones, T. W. et al., 1982. Cis-diamminedichlorplatinum-induced acute renal failure in the rat.Kidney Int 21:54.

[3]Daugaard, G., 1990. Cisplatin nephrotoxicity:experimental and clinical studies.Dan Med Bull 37:1.

[4]Goldstein, L., 1975. Glutamine transport by mitochondria isolated from normal and acidotic rats.Am J Physiol 229:1027.

[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.