Felemban Shatha G, Aldubayan Maha A, Alhowail Ahmad H, Almami Ibtesam S
Department of Medical Laboratory Sciences, Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia.
Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Saudi Arabia.
Oxid Med Cell Longev. 2020 Oct 27;2020:4372719. doi: 10.1155/2020/4372719. eCollection 2020.
Methotrexate (MTX; 4-amino-10-methylfolic acid) is a folic acid reductase inhibitor used to treat autoimmune diseases and certain types of cancer. Testicular toxicity resulting from MTX is a significant side effect that may cause subsequent infertility. The present study was conducted to examine the ameliorating effects of vitamin B17 (VitB17) against testicular toxicity induced by MTX in male rats. A total of 50 male albino rats were equally divided into five groups [control group; vitamin B17 group (VitB17) administered VitB17 only; methotrexate group administered MTX only; cotreated group, (VitB17+MTX) and posttreated group (MTX+VitB17)]. In methotrexate group (MTX), a significant decrease was observed in body weight and the testicular weight, as well as the levels of plasma testosterone, luteinizing hormone and follicle-stimulating hormone compared with control. The sperm count, viability, morphology index, total motility, and progressive motility also decreased in MTX rats compared with control. Furthermore, the levels of reduced glutathione, catalase, and superoxide dismutase, as well as proliferating cell nuclear antigen protein expression, in the testicular tissue decreased in MTX compared with control. In addition, MTX caused a significant increase in DNA and tissue damage compared with control. However, VitB17 ameliorated these effects, indicating that it has a preventative and curative effect against MTX-induced reproductive toxicity in male rats. The protective effect of VitB17 may be associated to its antioxidant properties as it possibly acts as a free-radical scavenger and lipid peroxidation inhibitor, as well as its protective effect on the levels of GSH, SOD, and CAT.
甲氨蝶呤(MTX;4-氨基-10-甲基叶酸)是一种叶酸还原酶抑制剂,用于治疗自身免疫性疾病和某些类型的癌症。MTX导致的睾丸毒性是一种显著的副作用,可能会导致后续的不育。本研究旨在探讨维生素B17(VitB17)对MTX诱导的雄性大鼠睾丸毒性的改善作用。总共50只雄性白化大鼠被平均分为五组[对照组;仅给予VitB17的维生素B17组(VitB17);仅给予MTX的甲氨蝶呤组;联合治疗组(VitB17+MTX)和后续治疗组(MTX+VitB17)]。与对照组相比,甲氨蝶呤组(MTX)的体重、睾丸重量以及血浆睾酮、黄体生成素和促卵泡激素水平均显著降低。与对照组相比,MTX大鼠的精子计数、活力、形态指数、总运动能力和渐进性运动能力也有所下降。此外,与对照组相比,MTX组睾丸组织中还原型谷胱甘肽、过氧化氢酶和超氧化物歧化酶的水平以及增殖细胞核抗原蛋白表达均降低。此外,与对照组相比,MTX导致DNA和组织损伤显著增加。然而,VitB17改善了这些影响,表明它对MTX诱导的雄性大鼠生殖毒性具有预防和治疗作用。VitB17的保护作用可能与其抗氧化特性有关,因为它可能作为自由基清除剂和脂质过氧化抑制剂发挥作用,以及对谷胱甘肽、超氧化物歧化酶和过氧化氢酶水平的保护作用。