Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity

Abstract

cis-Diamminedichloroplatinum (II) (cisplatin) is an important chemotherapeutic agent useful in the treatment of several cancers; however, it has several side effects such as nephrotoxicity. The role of the oxidative and nitrosative stress in cisplatin-induced nephrotoxicity is additionally supported by the protective effect of several free radical scavengers and antioxidants. Furthermore, in in vitro experiments, antioxidants or reactive oxygen species (ROS) scavengers have a cytoprotective effect on cells exposed to cisplatin. Recently, the participation of nitrosative stress has been more explored in cisplatin-induced renal damage. The use of a water-soluble Fe(III) porphyrin complex able to metabolize peroxynitrite (ONOO(-)) has demonstrated that this anion contributes to both in vivo and in vitro cisplatin-induced toxicity. ONOO(-) is produced when nitric oxide (NO*) reacts with superoxide anion (O(2)(*-)); currently, there are evidences suggesting alterations in NO* production after cisplatin treatment and the evidence appear to NO* has a toxic effect. This article goes through current evidence of the mechanism by more than a few compounds have beneficial effects on cisplatin-induced nephrotoxicity, contribute to understanding the role of oxidative and nitrosative stress and suggest several points as part of the mechanism of cisplatin toxicity.