Korean J Nephrol.  2002 Mar;21(2):213-221.

Role of Hydroxyl Radicals and Lipid Peroxidation in Cisplatin-induced Acute Renal Failure in Rabbits

Affiliations
  • 1Department of Internal Medicine, College of Medicine, Pusan National University, Pusan, Korea. kim430@pusan.ac.kr
  • 2Department of Physiology, College of Medicine, Pusan National University, Pusan, Korea.

Abstract

PURPOSE: This study was undertaken to determine whether lipid peroxidation induced by hydroxyl radicals play a critical role in cisplatin(cis-diamminedichloroplatinum II)-induced acute renal failure.
METHODS
Animals received cisplatin at a single i.p. dose of 5 mg/kg, and changes in renal function were measured at 48 hr after cisplatin injection.
RESULTS
Cisplatin caused an increase in serum creatinine level, which was accompanied by reduction in GFR. The fractional excretion of Na(+), glucose, and inorganic phosphate was increased in animals treated with cisplatin alone. Cisplatin treatment in vivo inhibited PAH uptake by renal cortical slices and Na(+)-K(+)-ATPase activity in microsomal fraction. Lipid peroxidation was increased in cisplatin-treated kidneys. When animals received the antioxidant N,N'-diphenyl-p-phenylenediamine(DPPD), the iron chelator deferoxamine, and hydroxyl radical scavengers dimethylthiourea and sodium benzoate before cisplatin injection, alterations in renal function and lipid peroxidation induced by cisplatin were significantly prevented. Exposure of renal cortical slices to cisplatin in vitro caused an increase in LDH release and lipid peroxidation, which were completely prevented by DPPD and deferoxamine. By contrast, hydroxyl radical scavengers(dimethylthiourea and thiourea) did not prevent cisplatin-induced LDH release despite they inhibited cisplatin-induced lipid peroxidation.
CONCLUSION
These results suggest that the lipid peroxidation resulting from generation of hydroxyl radicals may play a role in cisplatin-induced acute renal failure. In addition, the protective effects of hydroxyl radical scavengers in vivo studies are different from the results obtained from in vitro studies using renal cortical slices.

Keyword

Cisplatin; Reactive oxygen species; Lipid peroxidation; Iron chelator; Rabbits

MeSH Terms

Acute Kidney Injury*
Animals
Cisplatin
Creatinine
Deferoxamine
Glucose
Hydroxyl Radical
Iron
Kidney
Lipid Peroxidation*
Rabbits*
Reactive Oxygen Species
Sodium Benzoate
Cisplatin
Creatinine
Deferoxamine
Glucose
Hydroxyl Radical
Iron
Reactive Oxygen Species
Sodium Benzoate
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