Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity

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 center dot) reacts with superoxide anion (O-2(center dot-)); currently, there are evidences suggesting alterations in NO center dot production after cisplatin treatment and the evidence appear to NO center dot 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. (c) 2008 Elsevier GmbH. All rights reserved.