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*) 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.
Chirino
Yolanda I
YI
Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Tlalpan, DF, Mexico. irasema_chirino@yahoo.com.mx
Pedraza-Chaverri
José
J
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced*; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*
D000970:Antineoplastic Agents; D005609:Free Radicals; D016877:Oxidants; D002945:Cisplatin