Department of Medical Pharmacology, School of Medicine, Mustafa Kemal University, Hatay, 01330, Turkey.
Department of Biochemistry, Sanlıurfa Mehmet Akif İnan Training and Research Hospital, Sanlıurfa, Turkey.
Biomed Pharmacother. 2018 Jan;97:1486-1492. doi: 10.1016/j.biopha.2017.11.078. Epub 2017 Nov 20.
Methotrexate (MTX) is frequently used in the treatment of several diseases including cancers, rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, and dermatomyositis. Previously, chemotherapeutic agents have been reported to cause permanent azoospermia and infertility in men. Methotrexate has been also shown to damage the seminiferous tubules of the testicles, lower the sperm count, and cause genetic mutations (in DNA) in sperm. In this study, we aimed to investigate the protective effects of alpha lipoic acid (ALA) on MTX-induced testicle damage in a rat model. A total of 40 male Wistar Albino rats were used in this study. The rats were divided into four groups including 10 rats in each. The first group (control group) received only saline intraperitoneal (i.p.); the second group (ALA group) was given ALA 100 mg/kg i.p.; the third group (MTX group) received single dose MTX 20 mg/kg i.p.; and the fourth group (MTX + ALA group) received single dose MTX 20 mg/kg i.p. and ALA 100 mg/kg i.p. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), myeloperoxidase (MPO) levels in the testicular tissue and serum testosterone, serum total antioxidant status (TAS) and total oxidant status (TOS) levels were biochemically evaluated. Testicular tissues histopathologically evaluated. In the MTX group, the MDA, TAS and TOS levels were higher, while the SOD, CAT, GPx, MPO and serum testosterone levels decreased. Compared to the MTX group, the MDA, TAS and TOS levels were lower and the SOD, CAT, GPx, MPO and serum testosterone levels increased in the MTX + ALA group. In the histopathological examination, the mean seminiferous tubule length (MSTD), germinal epithelial cell thickness (GECT), and mean testicular biopsy score (MTBS) were found to significantly decrease in the MTX group, compared to the control group. These values were significantly higher in the MTX + ALA group, compared to the MTX group (p < 0.05). In our experimental study, MTX caused severe tissue destruction in testicles by increasing the formation of free oxygen radicals. Based on our study results, we suggest that, as a potent free radical scavenger, ALA can reduce MTX-induced testicular tissue damage thanks to its antioxidant and anti-inflammatory properties.
甲硫氨酸（MTX）常用于治疗多种疾病，包括癌症、类风湿性关节炎、银屑病关节炎、系统性红斑狼疮和皮肌炎。先前有报道称，化疗药物会导致男性永久性无精症和不育。甲硫氨酸已被证明会损害睾丸的生精小管，降低精子数量，并导致精子中的遗传突变（在 DNA 中）。在这项研究中，我们旨在研究α-硫辛酸（ALA）对 MTX 诱导的大鼠模型睾丸损伤的保护作用。总共使用了 40 只雄性 Wistar 白化大鼠进行这项研究。这些大鼠被分为四组，每组 10 只。第一组（对照组）仅接受腹腔内生理盐水（i.p.）；第二组（ALA 组）给予 ALA 100mg/kg i.p.；第三组（MTX 组）接受单次 MTX 20mg/kg i.p.；第四组（MTX+ALA 组）接受单次 MTX 20mg/kg i.p.和 ALA 100mg/kg i.p.。睾丸组织和血清中的丙二醛（MDA）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）、髓过氧化物酶（MPO）水平以及血清睾酮、血清总抗氧化状态（TAS）和总氧化状态（TOS）水平进行了生化评估。睾丸组织进行了组织病理学评估。在 MTX 组中，MDA、TAS 和 TOS 水平升高，而 SOD、CAT、GPx、MPO 和血清睾酮水平降低。与 MTX 组相比，MTX+ALA 组的 MDA、TAS 和 TOS 水平较低，SOD、CAT、GPx、MPO 和血清睾酮水平升高。在组织病理学检查中，与对照组相比，MTX 组的平均生精小管长度（MSTD）、生殖上皮细胞厚度（GECT）和平均睾丸活检评分（MTBS）显著降低。与 MTX 组相比，MTX+ALA 组的值显著升高（p<0.05）。在我们的实验研究中，MTX 通过增加自由基的形成，导致睾丸组织严重破坏。基于我们的研究结果，我们认为，作为一种有效的自由基清除剂，ALA 可以通过其抗氧化和抗炎特性，减少 MTX 诱导的睾丸组织损伤。
