Effect of desferrioxamine on cisplatin-induced nephrotoxicity in normal rats.
Biochemical and histological evaluations of the effects of the iron chelator desferrioxamine on the nephrotoxicity induced by cisplatin in normal rats were carried out. A single dose of cisplatin (7.5 mg/kg, intravenously) caused nephrotoxicity that manifested biochemically as an elevation of blood urea nitrogen, serum creatinine and an increase in the kidney weight as a percent of body weight. Moreover, severe decreases in serum calcium and albumin were observed. Histopathological examination of kidney tissue revealed tubular necrosis with sloughing of tubular epithelium. Desferrioxamine treatment (250 mg/kg, intraperitoneally) 30 min before cisplatin administration does not protect the kidney from the damaging effects of cisplatin. A greater increase in blood urea nitrogen, serum creatinine and kidney weight was observed with significant tubular necrosis and a mild lymphocytic infiltrate. Desferrioxamine pretreatment decreased the lipid peroxidation induced by cisplatin but at the same time increased nonprotein sulfhydryl (-SH) concentrations in the kidney tissue. The findings of this study suggest that lipid peroxidation is not the main cause of cisplatin-induced nephrotoxicity and that desferrioxamine which was useful for prevention of cardiac and hematological damage induced by doxorubicin, aggrevated the cisplatin-induced nephrotoxicity. More investigations are needed to establish a definite assessment of its selectivity.
al-Harbi
M M
MM
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Osman
A M
AM
al-Gharably
N M
NM
al-Bekairi
A M
AM
al-Shabanah
O A
OA
Sabah
D M
DM
Raza
M
M
D000818:Animals; D002945:Cisplatin / Q000493:pharmacokinetics / Q000633:toxicity*; D003676:Deferoxamine / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D010984:Platinum / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar
D010984:Platinum; D005978:Glutathione; D003676:Deferoxamine; D002945:Cisplatin