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阿齐沙坦作为雄性大鼠环磷酰胺诱导的睾丸损伤的预防剂。

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

作者信息

Ahmed Haneen Alaa, Gatea Fouad Kadhim, Hussein Zeena Ayad

机构信息

Department of Pharmacology, College of Medicine, Al-Nahrain University, Baghdad, Iraq.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan;398(1):979-990. doi: 10.1007/s00210-024-03339-6. Epub 2024 Aug 2.

Abstract

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 × 10/mm), sperm motility (30 vs. 90%), abnormal sperm (30.32 vs. 14.43%), dead sperm count (32.43 vs. 10.49 × 10/mm), DNA fragmentation (21.57 vs. 5.49%); meanwhile, azilsartan prevent these effects on median sperm count (17.0 × 10/mm), sperm motility (70.0%), abnormal sperm (23.19%), dead sperm count (26.17 × 10/mm), 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.

摘要

环磷酰胺(CP)是一种常用的癌症治疗药物;然而,尽管其疗效显著,但已知它会对睾丸造成损害。为了减轻CP对雄性大鼠生殖系统的损害,我们研究了阿齐沙坦(AZ)对CP诱导的睾丸损伤的保护作用。将30只Sprague-Dawley雄性大鼠平均分为三组:正常对照组:给予0.5%羧甲基纤维素(CMC)混悬液,持续13天;诱导组:在第6天腹腔注射(IP)200 mg/kg的CP单剂量;阿齐沙坦组:口服阿齐沙坦(4 mg/kg)5天,然后在第6天腹腔注射200 mg/kg的CP单剂量,之后再次给予阿齐沙坦7天。在第14天处死动物,评估精子特征、睾酮水平和睾丸组织病理学。与正常对照组相比,CP诱导导致精子计数中位数显著降低(12.0对22.0×10/mm)、精子活力(30%对90%)、异常精子(30.32%对14.43%)、死精子计数(32.43对10.49×10/mm)、DNA碎片化(21.57%对5.49%);同时,与CP组相比,阿齐沙坦可预防这些对精子计数中位数(17.0×10/mm)、精子活力(70.0%)、异常精子(23.19%)、死精子计数(26.17×10/mm)、DNA碎片化(13.81%)的影响,并改善血浆睾酮水平,还可预防睾丸的组织病理学改变。阿齐沙坦减轻CP的作用表明它可以预防CP对雄性大鼠的生殖损害。AZ具有保护作用的一个可能解释是它抑制脂质过氧化并具有抗氧化特性。

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