The effect of daily intraperitoneal injection of Deferoxamine in an acute model of Cisplatin induced nephrotoxicity

Abstract

Cisplatin is a major classical anticancer agents. However, cisplatin induced nephrotoxicity remains a major dose limiting side effect. Several studies has highlighted the role of catalytic iron content in several diseases including cispatin nephrotoxicity opening the doors for adding iron chelators as an adjunct therapy to cisplatin therapy. Since deferoxamine is the major approved chelation therapy in iron overload disorders, the current study was directed to exploring the possible nehroprotective outcomes of deferoxamine in an acute animal model of cisplatin induced renal injury. Male Spargue-Dawley rats were injected i.p. daily for 6 consecutive days with 3 different dose levels of deferoxamine as follows: 100, 200 and 300 mg/kg. On day 3, cisplatin was injected i.p. as a single dose of 7.5 mg/kg and animals were sacrificed on day 7. Measurement of serum creatinine and blood urea nitrogen (BUN) showed that iron chelation by deferoxamine failed to improve kidney function as demonstrated by the consistent high creatinine and BUN levels in all the treated groups. Calculation of kidney indices further confirmed the previous measurements. Histopathological examination of the renal tissues of animals showed the development of tubular degeneration in all treated groups indicating the absence of significant nephroprotection. In conclusion, our results show that the daily i.p. injection of deferoxamine is not protective against cisplatin induced acute renal injury. However, the well-established body of evidence supporting the potential contribution of catalytic iron in cisplatin induced nephrotoxicity establishes the demand for investigating the potential nephroprotective effects of other established iron chelation therapies.

Keywords

• cisplatin
• deferoxamine
• acute renal injury
• catalytic iron
• intraperitoneal
• chelation therapy