Effects of the diuretics mannitol or acetazolamide on nephrotoxicity and physiological disposition of cisplatin in rats

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Abstract
The anticancer drug cisplatin has been known to produce severe renal lesions characterized by high levels of blood urea nitrogen (BUN), toxic nephrosis, and platinum (Pt) retention in the kidney. The effect of IV pretreatment with acetazolamide (ACZ) 30 min before or mannitol (MAN) immediately prior to IP administration of 5 mg/kg cisplatin on Pt excretion, tissue distribution, and nephrotoxicity was investigated in male F344 rats. ACZ pretreatment reduced the cisplatin-induced nephrotoxicity, as indicated by only a slight elevation of BUN, a milder histopathologic lesion, and a more rapid recovery of renal function and structure. Although MAN-pretreated animals exhibited similar changes in BUN to ACZ-pretreated animals, the renal damage was similar to that seen in aninals treated with cisplatin alone. A reduction of kidney Pt content was observed with both diuretics, although there was significantly less retention after ACZ pretreatment. The diuretic ACZ was more effective than MAN in reducing the renal lesions induced by cisplatin and it might be clinically useful in preventing cisplatin nephrotoxicity.