Sex Difference in Cisplatin-Induced Nephrotoxicity: Laboratory and Clinical Findings

Cisplatin (CP) as the most important anticancer drug has limited usage due to a lot of side effects such as nephrotoxicity. Additionally, nephrotoxicity is gender/sex-related. There is a variety of experimental studies in association with sex and CP-induced nephrotoxicity. Some studies have reported that female sex is resistant than male sex due to greater antioxidant defense and protective effects of estrogen in females. Other studies have indicated that males are less vulnerable than females due to CP high clearance. Also, various supplementations have revealed conflicting effects in males and females. It is uncovered that sex hormones have determinant roles on the conflicting effects. Some supplements could improve CP-induced nephrotoxicity, but several supplements intensified CP-induced nephrotoxicity, especially in female sex. On the other hand, major clinical studies introduced female gender as a risk factor of CP-induced nephrotoxicity. Although, rare studies evaluated the effect of various supplemental compounds on CP-induced nephrotoxicity in patients underwent CP therapy. Therefore, it requires further investigations to clarify the controversial subject of gender/sex and CP-induced nephrotoxicity in both clinic and laboratory.