Attenuation of cisplatin nephrotoxicity by streptozotocin-induced diabetes.
The therapeutic 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 nephrotoxicity 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 (PAH) 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 normoglycemic 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, glucosuria, and proteinuria were measured in normoglycemic rats 4 days after cisplatin administration. Renal cortical TEA and lactate-stimulated PAH uptake (p less than 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, proteinuria, glucosuria and elevated kidney weight. These results indicate that the diabetic state attenuates cisplatin nephrotoxicity. Additionally, these results indicate that diabetes attenuation of cisplatin nephrotoxicity is dependent on the severity of the diabetic state.
Scott
L A
LA
Department of Pharmacology, Marshall University School of Medicine, Huntington, West Virginia 25755-9310.
Madan
E
E
Valentovic
M A
MA
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D007477:Ions / Q000378:metabolism; D007668:Kidney / Q000187:drug effects; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014563:Urodynamics / Q000187:drug effects
D001786:Blood Glucose; D007477:Ions; D002945:Cisplatin