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© 1989 Oxford University Press

research-article

Attenuation of Cisplatin Nephrotoxicity by Streptozotocin-Induced Diabetes1

LAURIE A. SCOTT, ELIO MADAN and MONICA A. VALENTOVIC2

Departments of Pharmacology and Pathology, Marshall University School of Medicine Huntington, West Virginia 25755-9310

Received May 25, 1988; accepted September 13, 1988

Attenuation of Cisplatin Nephrotoxicity by Streptozotocin-Induced Diabetes. SCOTT, L. A., MADAN, E., AND VALENTOVIC, M. A. (1989). Fundam. Appl. Toxicol 12, 530–539. The thera peutic use of cisplatin is associated with acute renal failure. The purpose of this study was to determine (a) if streptozotocin (STZ) was toxic to renal proximal tubules and (b) the nephrotox icity of cisplatin in STZ-diabetic rats. Male Sprague-Dawley rats were injected with STZ (55 mg/kg, ip) to induce a diabetic state. BUN and renal cortical slice uptake of p-aminohippurate (PAN) and tetraethylammonium (TEA) were not altered, relative to normoglycemic rats, 3, 16, and 28 days following STZ treatment. These results indicate that STZ is not toxic to renal proximal tubules. Cisplatin nephrotoxicity studies were then conducted in STZ-diabetic and normo glycemic rats. Cisplatin nephrotoxicity was also evaluated in diabetic rats pretreated for 8 days with insulin. Diabetic and normoglycemic rats were administered 5 mg/kg cisplatin or water (ip). Increased kidney weight, BUN levels, glucosuna, and proteinuria were measured in normoglycemic rats 4 days after cisplatin administration. Renal cortical TEA and lactate-stimulated PAH uptake (p<0.05) were diminished in the normoglycemic rats 4 days after cisplatin injection. No change in kidney weight, BUN levels, or renal cortical slice accumulation of PAH and TEA was observed in diabetic rats treated with cisplatin. However, cisplatin administration to diabetic rats pretreated with insulin resulted in increased mortality, proteinurla, glucosuna and elevated kidney weight. These results indicate that the diabetic state attenuates cisplatin nephro toxicity. Additionally, these results indicate that diabetes attenuation ofcisplatin nephrotoxicity is dependent on the severity of the diabetic state.


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