Telmisartan protects male reproductive function by modulating biochemical, oxidative stress, apoptosis, and DNA integrity in cyclophosphamide-exposed rats.

BACKGROUND

Cyclophosphamide (CPA) is a common chemotherapy drug known to cause significant damage to testicular health. It induces oxidative stress, inflammation, cell death, and DNA damage. Telmisartan blocks the angiotensin II type 1 receptor and has some activity on PPAR-γ, a receptor involved in cell regulation. It has been shown to have antioxidant and cell-protecting effects in other organs, but its potential to safeguard reproductive health has not been thoroughly investigated.

OBJECTIVE

This study aimed to evaluate the protection exerted by telmisartan against CPA-induced testicular injury in rats, addressing its anti-inflammatory and anti-apoptotic mechanisms.

METHODS

56 adult male Sprague-Dawley rats were randomized into seven groups: control, telmisartan control, CPA induction, three telmisartan treatment groups (3, 5, and 7 mg/kg/day), and a melatonin positive control. Treatments have been given for 8 days; CPA (150 mg/kg, i.p.) on the second day. The serum reproductive hormones, sperm quality, oxidative stress factors, apoptotic genes (Bax, Bcl-2, caspase-3), DNA fragmentation, and histopathology were assessed.

RESULTS

CPA inhibited testosterone, LH, and FSH, decreased sperm quality, increased oxidative stress, proapoptotic markers, and induced DNA fragmentation. Telmisartan improved all of these parameters by administration on a dose-dependent basis, and the treatment with higher doses returned hormone levels, sperm quality, antioxidant defenses and apoptotic balance back to near-normal levels. Telmisartan had similar protective actions to those of melatonin, given at high doses.

CONCLUSION

Telmisartan protects from CPA-related testicular toxicity via anti-inflammatory and anti-apoptotic actions.