Renal metallothionein and platinum levels in diabetic and nondiabetic rats injected with cisplatin.
This study was designed to investigate the relationship between the attenuation of cisplatin-induced nephrotoxicity in experimental diabetes and the increased level of renal metallothionein (MT) reported to occur in this condition. Two groups of male Sprague-Dawley rats were used: 42-day streptozotocin diabetics and age-matched nondiabetics. Half of each group was injected with a nephrotoxic dose of cisplatin (5 mg/kg, ip) and half with vehicle. Four hours after injection, renal MT and platinum (Pt) content were quantified. Mean renal MT concentration in vehicle-injected diabetics was about triple that found in nondiabetics. Comparison of renal MT concentrations in cisplatin-injected diabetics and nondiabetics with their vehicle-injected counterparts suggested an inducing effect of the drug. In contrast to the marked elevations of MT in diabetic kidney, mean renal Pt concentration in the cisplatin-injected diabetic group was only about one-fourth that of the nondiabetic group. No difference was evident in the intracellular distribution Pt between cytosolic and particulate fractions from diabetic and nondiabetic kidneys. It was concluded that: (i) Sequestration of Pt by MT cannot account for the resistance of diabetic kidney to cisplatin toxicity. (ii) Rather, the resistance is due to a significant decrease in renal uptake/retention of cisplatin or derivatives during the critical first few hours after injection.
Cacini
W
W
Division of Pharmacology and Medicinal Chemistry, College of Pharmacy, University of Cincinnati Medical Center, Ohio 45267-0004.
Singh
Y
Y
D000818:Animals; D002945:Cisplatin / Q000378:metabolism / Q000633:toxicity*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007668:Kidney / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D008668:Metallothionein / Q000032:analysis*; D010984:Platinum / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains
D010984:Platinum; D008668:Metallothionein; D002945:Cisplatin