文献DOI：10.1016/j.biopha.2017.11.078
文献PMID：29793311
文献原文链接：http://doi.org.sci-hub.tw/10.1016/j.biopha.2017.11.078
Biomedicine & Pharmacotherapy 97 (2018) 1486–1492
《The protective effects of alpha lipoic acid on methotrexate induced testis injury in rats》
α硫辛酸对甲氨蝶呤致大鼠睾丸损伤的保护作用
【Abstract】
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.
摘要翻译：
甲氨蝶呤（MTX）经常用于治疗多种疾病，包括癌症、类风湿性关节炎、银屑病性关节炎、系统性红斑狼疮和皮肌炎。以前，据报道，化学治疗剂会导致男性患有永久性无精子症和不育症。甲氨喋呤也被证明会破坏睾丸的曲细精管，降低精子数量，并导致精子中的基因突变（在DNA中）。在这项研究中，我们旨在研究α硫辛酸（ALA）对大鼠模型中MTX诱导的睾丸损伤的保护作用。在该研究中共使用40只雄性Wistar Albino大鼠。将大鼠分成4组，每组10只。第一组（对照组）仅接受盐水腹膜内（i.p.）；第二组（ALA组）给予ALA 100mg / kg i.p.；第三组（MTX组）接受单剂量MTX 20mg / kg i.p.；第四组（MTX + ALA组）接受单剂量MTX 20mg / kg i.p.和ALA 100 mg / kg i.p.。对丙二醛（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）、睾丸组织中的髓过氧化物酶（MPO）水平和血清睾酮、血清总抗氧化状态（TAS）和总氧化剂状态（TOS）水平进行了生物化学评估。睾丸组织进行组织病理学评估。在MTX组中，MDA、TAS和TOS水平较高，而SOD、CAT、GPx、MPO和血清睾酮水平下降。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组的生精小管平均长度（MSTD）、生发上皮细胞厚度（GECT）和平均睾丸活检评分（MTBS）显着降低。与MTX组相比，MTX + ALA组的这些值显着更高（p <0.05）。在我们的实验研究中，MTX通过增加游离氧自由基的形成在睾丸中引起严重的组织破坏。根据我们的研究结果，我们建议，作为一种有效的自由基清除剂，ALA可以减少MTX诱导的睾丸组织损伤，因为它具有抗氧化和抗炎特性。