Khedr Naglaa F, Werida Rehab H
Faculty of Pharmacy, Department of Biochemistry, Tanta University, Tanta, Egypt.
Faculty of Pharmacy, Clinical Pharmacy & Pharmacy Practice Department, Damanhur University, El- Bahiara, Egypt.
Life Sci. 2022 Feb 1;290:120025. doi: 10.1016/j.lfs.2021.120025. Epub 2021 Oct 9.
Trazadone is an antidepressant and may affect reproductive hormones and spermatogenesis. l-carnitine is an amino acid that exhibits antioxidant actions. This study was designed to investigate the potential protective effects of l-carnitine against trazadone-induced testicular toxicity in male rats and the possible underlying mechanisms such as oxidative stress, inflammation and autophagy.
thirty-two male Wistar rats were divided randomly into four equal groups (n = 8). Testicular damage was induced by oral administration of Trazadone (TRZ, 20 mg/kg/day, p.o.) for four weeks (TRZ group). l-carnitine (LC, 200 mg/kg/day, p.o.) was applied for four weeks (LC group). LC + TRZ group administered the same doses of LC and TRZ concomitantly. The control group received distilled water (as vehicle).
the protective treatment with LC attenuated the decline of sperm count and motility resulted from trazadone administration. Moreover, LC ameliorated trazadone increased lipid peroxidation (MDA) and reduction of total thiol and catalase activity. LC modulated the elevation in tumor necrosis factor- α (TNF-α), and increased the expression of autophagy related genes Becline-1, ATG 5 and ATG-12 in rat testes. Serum level of FSH, LH and total testosterone were increased significantly (p < 0.001) in LC + TRZ group. Histopathological findings further supported the protective effects of LC against trazadone -induced testicular injury by increasing free sperms within the lumen of spermatogenic cells and improving testicular degeneration.
These findings supported the protective effects of l-carnitine on rat testes due to suppression of oxidative stress, inflammation and enhancing autophagy. l-carnitine may be recommended as adjuvant therapy to trazadone treatment.
曲唑酮是一种抗抑郁药，可能会影响生殖激素和精子发生。左旋肉碱是一种具有抗氧化作用的氨基酸。本研究旨在探讨左旋肉碱对曲唑酮诱导的雄性大鼠睾丸毒性的潜在保护作用，以及氧化应激、炎症和自噬等可能的潜在机制。
32只雄性Wistar大鼠随机分为四组，每组8只。通过口服曲唑酮（TRZ，20mg/kg/天，口服）诱导睾丸损伤，持续四周（TRZ组）。应用左旋肉碱（LC，200mg/kg/天，口服）四周（LC组）。LC + TRZ组同时给予相同剂量的LC和TRZ。对照组给予蒸馏水（作为赋形剂）。
LC的保护性治疗减轻了曲唑酮给药导致的精子数量和活力的下降。此外，LC改善了曲唑酮引起的脂质过氧化（MDA）增加以及总硫醇和过氧化氢酶活性的降低。LC调节了肿瘤坏死因子-α（TNF-α）的升高，并增加了大鼠睾丸中自噬相关基因Beclin-1、ATG 5和ATG-12的表达。LC + TRZ组血清促卵泡生成素（FSH）、促黄体生成素（LH）和总睾酮水平显著升高（p < 0.001）。组织病理学结果进一步支持了LC对曲唑酮诱导的睾丸损伤的保护作用，表现为增加生精细胞腔内的游离精子数量并改善睾丸变性。
这些发现支持了左旋肉碱通过抑制氧化应激、炎症和增强自噬对大鼠睾丸的保护作用。左旋肉碱可推荐作为曲唑酮治疗的辅助疗法。
