“A Comparative Study Of The Potential Nephroprotective Effects Of Iron Chelators In Cisplatin Induced Nephrotoxicity”

Abstract

Cisplatin is one of the classical gold standard platinum-based anti-cancer agents that has long been used in the treatment of various cancers. However, cisplatin therapy is accompanied by major toxicities limiting its use. Of which, cisplatin-induced nephrotoxicity stands as a major toxicity affecting almost 33% of the patients and often leading to the termination of cisplatin therapy. Cisplatin-induced nephrotoxicity is a multi-factorial process that occurs due to the preferential accumulation of cisplatin within the kidneys, increased renal oxidative stress as well as the induction of apoptotic machineries and major inflammatory pathways. Recently, it has been reported that cisplatin therapy induces an increase in the catalytic iron content within the kidneys suggesting a potential role for iron chelators in ameliorating cisplatin-induced acute renal injury. Moreover, iron chelators have been reported to have potential anti-cancer activities attenuating cancer resistance to cisplatin chemotherapy. There are two principal iron chelators in the Egyptian market; deferoxamine (for parenteral administration) and deferiprone (for oral administration). Hence, the current study aimed to investigate and compare the potential nephroprotective activities of the iron chelators; deferoxamine and deferiprone in a rat model of cisplatin-induced acute renal injury as well as the potential underlying molecular mechanisms of renoprotection including their effects on oxidative stress, apoptosis and inflammation. Moreover, the effect of iron chelation therapy on ROCK2