Renal accumulation and urinary excretion of cisplatin in diabetic rats.
Previous work has demonstrated that cisplatin nephrotoxicity was attenuated in streptozotocin (STZ)-induced diabetic rats. The following studies investigated the hypothesis that renal cisplatin accumulation was reduced in diabetic rats. Male Fischer 344 (F344) rats were injected with 32 mg/kg STZ (i.p.) or citrate buffer. Renal platinum (Pt) accumulation was quantitated 0-96 h after the administration of 5 mg/kg cisplatin (i.p.) to normoglycemic and diabetic rats (greater than or equal to 4/group). Total renal Pt accumulation was decreased (P less than 0.05) in the diabetic rats, when compared to the normoglycemic group, 6-48 h after cisplatin injection. Further studies were also conducted to examine if urinary cisplatin excretion was enhanced in diabetic relative to normoglycemic groups. Urinary Pt excretion was quantitated 0-96 h following cisplatin (5 mg/kg, i.p.) administration. Pt excretion was increased in the diabetic group relative to the normoglycemics when comparisons were made on the basis of Pt excreted per hour or cumulative Pt excretion. Differences were also detected in urinary Pt concentration. The diabetic group had a lower urinary concentration of the metal 12-96 h after cisplatin injection. These findings suggest that the reduction in nephrotoxicity in diabetic rats may be at least partially due to decreased renal accumulation as well as altered renal excretion.
Valentovic
M A
MA
Dept. of Pharmacology, Marshall University School of Medicine, Huntington, WV 25755-9310.
Scott
L A
LA
Madan
E
E
Yokel
R A
RA
D000818:Animals; D001786:Blood Glucose; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000378:metabolism / Q000633:toxicity*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D013054:Spectrophotometry, Atomic
D001786:Blood Glucose; D002945:Cisplatin