Cisplatin Nephrotoxicity and Sexual Dimorphism: Experimental Trials for Protection

Abstract

Background: Cisplatin is one of the most commonly used anticancer agents either alone or in combination. Nephrotoxicity is the most common and distressing side effect of its usage. Many mechanisms have been reported for describing the pathogenesis of cisplatin-nephrotoxicity, including a severe inflammatory response, vascular injury, free radicals generation, toxic metabolites, and apoptotic pathways. Many experimental trials were done to prevent or ameliorate cisplatin nephrotoxicity using neutralizing agents, antioxidant agents, or herbal compounds with variable results. Sex/gender differences have a great role in the process of cisplatin-induced nephrotoxicity. Many experimental studies reported that female rats were more resistant to cisplatin nephrotoxicity than male rats. Many experimental trials were done using a variety of compounds including sex hormones, antioxidants, and plant extracts to discover their preventive effects on cisplatin-induced nephrotoxicity in male and female experimental models with variable results. Conclusion: There is still a need for further studies to discover effective strategies for combating this dangerous side effect of cisplatin treatment and its sexual dimorphism.