The role of oxygen free radicals in cisplatin-induced acute renal failure in rats.
We examined the role of oxygen free radicals in cisplatin-induced acute renal failure (ARF). The intravenous injection of cisplatin (5 mg/kg body weight) induced an increase in serum creatinine and tubular damage in the outer stripe of the outer medulla in rats. The renal content of malondialdehyde (MDA) transiently increased. Treatment with the free radical scavengers dimethylthiourea (DMTU) or lecithinized superoxide dismutase (L-SOD) attenuated the increase in serum creatinine. The beneficial effect of DMTU, a hydroxyl radical scavenger, was associated with less accumulation of MDA, less tubular damage, and enhanced expression of proliferating cell nuclear antigen (PCNA) in the damaged tubular cells, but not with improvement of reduced renal blood flow (RBF). On the other hand, the beneficial effect of L-SOD, a superoxide anion scavenger, was associated with preservation of RBF and increased urinary guanosine 3',5'-cyclic monophosphate excretion but not with modification of tubular damage or PCNA expression. These results suggest that (1) cisplatin-induced nephrotoxicity was associated with lipid peroxidation, (2) the hydroxyl radical scavenger prevented ARF through both attenuation of tubular damage and enhanced regenerative response of the damaged tubular cells, and (3) the superoxide anion scavenger did the same through preservation of RBF. It follows that oxygen free radicals may play an important role in cisplatin-induced ARF by reducing RBF and inducing tubular damage.
Matsushima
H
H
First Department of Medicine, Hamamatsu University School of Medicine, Japan.
Yonemura
K
K
Ohishi
K
K
Hishida
A
A
D000118:Acetylglucosaminidase / Q000652:urine; D058186:Acute Kidney Injury / Q000503:physiopathology*; D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D006152:Cyclic GMP / Q000652:urine; D016166:Free Radical Scavengers / Q000494:pharmacology; D007684:Kidney Tubules / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects; D013482:Superoxide Dismutase / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D016166:Free Radical Scavengers; D018809:Proliferating Cell Nuclear Antigen; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; C038983:1,3-dimethylthiourea; D003404:Creatinine; D013482:Superoxide Dismutase; D000118:Acetylglucosaminidase; D013890:Thiourea; D006152:Cyclic GMP; D002945:Cisplatin