Azilsartan as a preventive agent against cyclophosphamide-induced testicular injury in male rats

Cyclophosphamide (CP) is a popular cancer treatment; however, despite its efficacy, it is known to cause harm to the testicles. To mitigate the reproductive damage caused by CP in male rats, we examined the protective effect of azilsartan (AZ) on CP-induced testicular damage. Thirty Sprague-Dawley male rats were equally divided into three groups: normal control group: received 0.5% CMC suspension for 13 days; induction group: received a single dose of 200 mg/kg of CP on day 6 by intraperitoneal (IP) injection, azilsartan group: received azilsartan (4 mg/kg) orally for 5 days followed by a single dose of 200 mg/kg of (CP) on day 6 by IP injection, then azilsartan administered again for 7 days. Animals were sacrificed on day 14, and sperm characteristics, testosterone levels, and testicular histopathology were evaluated. Induction with CP caused a significant reduction in median value compared to normal control in sperm count (12.0 vs. 22.0 × 10⁶/mm³), sperm motility (30 vs. 90%), abnormal sperm (30.32 vs. 14.43%), dead sperm count (32.43 vs. 10.49 × 10⁶/mm³), DNA fragmentation (21.57 vs. 5.49%); meanwhile, azilsartan prevent these effects on median sperm count (17.0 × 10⁶/mm³), sperm motility (70.0%), abnormal sperm (23.19%), dead sperm count (26.17 × 10⁶/mm³), DNA fragmentation (13.81%), and improved plasmatic testosterone levels compared to the CP group and prevented histopathological alterations of the testes. Azilsartan's mitigation of CP's effects suggests it can prevent male rats' reproductive damage caused by CP. One possible explanation for AZ's protective effects is that it inhibits lipid peroxidation and has antioxidant properties.