Effect of Desferrioxamine on Cisplatin-induced Nephrotoxicity in Normal Rats

Abstract

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, aggravated the cisplatin-induced nephrotoxicity. More investigations are needed to establish a definite assessment of its selectivity.

REVERSAL OF CISPLATIN‐INDUCED CARNITINE DEFICIENCY AND ENERGY STARVATION BY PROPIONYL‐l‐CARNITINE IN RAT KIDNEY TISSUES

“…This imbalance between pro‐oxidants and anti‐oxidants, in favour of the former, causes the formation of oxidative stress (reactive oxygen species and free radicals) in kidney tissues. Thus, the observed increase in the levels of NO x and TBARS in kidney tissues in the present study is consistent with results of previous studies, which have demonstrated the involvement of oxidative stress, lipid peroxidation and mitochondrial dysfunction in CDDP‐induced nephrotoxicity 45–48 …”

Progression of Cisplatin-Induced Nephrotoxicity in a Carnitine-Depleted Rat Model

“…This speculation agreed with previous studies which have demonstrated the involvement of oxidative stress, lipid peroxidation, and mitochondrial dysfunction in cisplatin-induced nephrotoxicity [29, 30, 34, 35]. The contribution of NO to the cytotoxicity and organ toxicity of anticancer drugs has been previously reported [36, 37, 38].…”

Oral deferiprone administration ameliorates cisplatin-induced nephrotoxicity in rats

“…Based on enhanced lipid peroxidation induced by cisplatin, lipid peroxidation is considered another iron‐related mechanism that is important in cisplatin nephrotoxicity . The protective effects of hydroxyl radical scavengers and iron chelators in several in‐vitro and in‐vivo models of cisplatin‐induced renal failure have been largely taken as a reason for the iron‐mediated hydroxyl radical generation in tissue damage …”

“…The possible involvement of iron in cisplatin‐induced nephrotoxicity became evident from studies in which iron chelators (2,3‐dihydroxybenzoic acid or deferoxamine) were shown to be renal protective . However, as far as we know, the effect of deferiprone on cisplatin‐induced nephrotoxicity remains to be investigated.…”