Alshamrani Ali A, Al-Hamamah Mohammed A, Albekairi Norah A, Attia Mohamed S M, Ahmad Sheikh F, Assiri Mohammed A, Ansari Mushtaq A, Nadeem Ahmed, Bakheet Saleh A, Alanazi Wael A, Attia Sabry M
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Biomedicines. 2023 Sep 29;11(10):2674. doi: 10.3390/biomedicines11102674.
Diabetes mellitus is a metabolic disease that can cause systemic problems, including testicular dysfunction. Several diabetes medications have demonstrated potential adverse effects on the male reproductive system; however, the effects of saxagliptin and dapagliflozin have not been sufficiently examined. This investigation studied the impacts of saxagliptin and dapagliflozin treatments on the gonads in a male mouse model of diabetes. Testicular disturbances were assessed by sperm DNA damage, diakinesis-metaphase I chromosome examination, and spermiogram analysis. Our results showed more sperm DNA damage, more spermatocyte chromosome aberrations, lower sperm motility/count, and more sperm morphological anomalies in diabetic mice than in the control mice. Dapagliflozin significantly restored all examined measures to the control values in diabetic mice, unlike saxagliptin, which exacerbated the reduction in sperm count and motility. Both drugs significantly restored the gonadal redox imbalances in diabetic mice by decreasing reactive oxygen species accumulation and increasing glutathione levels. In conclusion, our study presents preliminary evidence for the safety and efficacy of dapagliflozin in alleviating testicular abnormalities induced by diabetes, making it a promising candidate drug for patients with diabetes in their reproductive age. As saxagliptin may have negative effects on fertility, its prescription should be avoided in young male diabetic patients.
糖尿病是一种可导致包括睾丸功能障碍在内的全身性问题的代谢性疾病。几种糖尿病药物已显示出对男性生殖系统的潜在不良影响；然而，沙格列汀和达格列净的影响尚未得到充分研究。本研究在雄性糖尿病小鼠模型中研究了沙格列汀和达格列净治疗对性腺的影响。通过精子DNA损伤、终变期-中期I染色体检查和精子图分析来评估睾丸功能障碍。我们的结果显示，与对照小鼠相比，糖尿病小鼠的精子DNA损伤更多、精母细胞染色体畸变更多、精子活力/数量更低以及精子形态异常更多。与沙格列汀不同，达格列净可将糖尿病小鼠所有检测指标显著恢复至对照值，而沙格列汀会加剧精子数量和活力的降低。两种药物均通过减少活性氧积累和增加谷胱甘肽水平，显著恢复了糖尿病小鼠的性腺氧化还原失衡。总之，我们的研究为达格列净缓解糖尿病诱导的睾丸异常的安全性和有效性提供了初步证据，使其成为育龄期糖尿病患者有前景的候选药物。由于沙格列汀可能对生育能力有负面影响，年轻男性糖尿病患者应避免使用该药。
