Taxifolin mitigates cisplatin-induced testicular damage by reducing inflammation, oxidative stress, and apoptosis in mice.

Abstract

Cisplatin (CIS) is effective against various cancers but causes significant side effects, including testicular damage. This study investigated the effects of taxifolin (TX), a potent flavonoid with well-known benefits, against CIS-induced testicular injury. Mice received TX (25 and 50 mg/kg) orally for 14 days, with a single injection of CIS (7 mg/kg) on day 8. CIS significantly impaired sperm parameters (motility, viability, and count) and caused notable histopathological alterations in testicular tissue. CIS-treated testicular tissue exhibited elevated MDA and protein carbonyl levels, alongside decreased antioxidant defenses, including GSH, SOD, and catalase activities. TX significantly mitigated the deterioration of sperm parameters and prevented testicular tissue damage. It also restored antioxidant levels and reduced MDA and protein carbonyl contents. Furthermore, CIS elevated pro-inflammatory markers (NF-κB p65, TNF-α, and IL-1β) and apoptosis markers (Bax and caspase-3), while reducing anti-apoptotic Bcl-2 levels. TX effectively suppressed NF-κB activation, reduced pro-inflammatory cytokine production, and inhibited apoptosis in CIS-treated mice. Overall, TX alleviated CIS-induced oxidative stress, inflammation, apoptosis, and testicular damage, thereby improving sperm quality. These findings emphasize TX's potential as a protective agent against CIS-induced testicular damage and warrant further research in human applications.