Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Clinical Sciences, Faculty of Veterinary Medicine, Razi University, Kermanshah, Iran.
Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Anatomical Sciences, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Reprod Toxicol. 2023 Jun;118:108368. doi: 10.1016/j.reprotox.2023.108368. Epub 2023 Mar 24.
Citalopram is the most potent selective serotonin reuptake inhibitor, commonly prescribed as an antidepressant, which can cause sexual dysfunction. Melatonin is a natural, highly effective antioxidant playing a pivotal role in the male reproductive system. The present study aimed to explore the ameliorating potential of melatonin on citalopram-evoked testicular toxicity and injury in mice. In this regard, mice were randomly divided into six groups: control, citalopram, melatonin 10 mg/kg, melatonin 20 mg/kg, melatonin 10 mg/kg plus citalopram, and melatonin 20 mg/kg plus citalopram. Adult male mice were intraperitoneally (i.p.) injected with 10 mg/kg of citalopram for 35 days with or without melatonin. At the end of the study, sperm parameters, testosterone level, testicular levels of malondialdehyde (MDA), nitric oxide (NO), total antioxidant capacity (TAC), and apoptosis (Tunel essay) were evaluated. Our findings revealed that melatonin restored spermatogenesis by improving sperm count, motility, viability, morphology, and chromatin integrity. Testosterone levels and the histopathology of the testes were markedly improved in the melatonin-administrated groups. Furthermore, citalopram administration significantly increased oxidative stress; however, melatonin restored antioxidant status by enhancing TAC levels and decreasing NO and MAD levels. More notably, citalopram therapy induced a significant increase in the number of Tunel-positive cells, while melatonin administration significantly mitigated the apoptotic impacts of citalopram. Together, melatonin therapy provides protection against citalopram-induced testicular damage via modulating nitro-oxidative stress and apoptosis, which provides evidence for melatonin as a promising treatment against antidepressant drug-associated reproductive toxicity and male sub/infertility.
西酞普兰是最强效的选择性 5-羟色胺再摄取抑制剂，通常被开为抗抑郁药，可引起性功能障碍。褪黑素是一种天然的、高效的抗氧化剂，在男性生殖系统中起着关键作用。本研究旨在探讨褪黑素对西酞普兰诱发的小鼠睾丸毒性和损伤的改善作用。为此，将小鼠随机分为六组：对照组、西酞普兰组、褪黑素 10mg/kg 组、褪黑素 20mg/kg 组、褪黑素 10mg/kg 加西酞普兰组和褪黑素 20mg/kg 加西酞普兰组。成年雄性小鼠连续 35 天腹腔注射 10mg/kg 的西酞普兰，同时或不给予褪黑素。研究结束时，评估精子参数、睾酮水平、睾丸丙二醛（MDA）、一氧化氮（NO）、总抗氧化能力（TAC）和凋亡（Tunel 法）水平。我们的研究结果表明，褪黑素通过提高精子计数、活力、存活率、形态和染色质完整性来恢复精子发生。褪黑素给药组的睾酮水平和睾丸组织病理学明显改善。此外，西酞普兰给药显著增加氧化应激；然而，褪黑素通过提高 TAC 水平和降低 NO 和 MAD 水平来恢复抗氧化状态。更值得注意的是，西酞普兰治疗导致 Tunel 阳性细胞数量显著增加，而褪黑素给药显著减轻了西酞普兰的凋亡作用。综上所述，褪黑素通过调节硝基氧化应激和凋亡，为治疗抗抑郁药相关生殖毒性和男性亚/不育症提供了证据，为西酞普兰引起的睾丸损伤提供了保护作用。
