Said Riham Soliman, Mohamed Heba A, Kassem Dina Hamada
Department of Drug Radiation Research, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt.
Department of Drug Radiation Research, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt.
Toxicology. 2020 Sep;442:152536. doi: 10.1016/j.tox.2020.152536. Epub 2020 Jul 7.
Radiotherapy is one of the principal approaches employed in the treatment of pelvic cancers. Nevertheless, testicular dysfunction and infertility are among the most common adverse effects in young adult cancer survivors. Clinically, alpha-lipoic acid (LA) has been applied to improve the quality of sperm with a satisfactory effect. Therefore, the present study investigated the underlying mechanisms of the radioprotective effects of LA against testicular damage. Male Sprague-Dawley rats were exposed to 10 Gy of whole-body ϒ-radiation and LA (50 mg/kg, P.O.) was administered one week before and three days post-irradiation. LA showed remarkable capacity in preserving testicular tissue against radiation damage by improving histological and ultrastructural changes of disorganized seminiferous tubules, besides enhancing its diameter, germinal epithelial thickness, and Johnsen's score. Radiation instigated a significant decrease in sperm quality and quantity associated with depletion of serum testosterone levels, while the LA administration maintained spermatogenesis. Strikingly, LA exhibited antioxidant properties by restoring reduced glutathione levels and antioxidant enzyme activities such as catalase and glutathione-s-transferase, besides diminishing malondialdehyde levels in the testis of irradiated group. Furthermore, LA alleviated testicular inflammation through downregulation of nuclear factor-ĸB (NF-ĸB) expression with a subsequent reduction in interleukin (IL)-6 and cyclooxygenase-2 expression, accompanied by the augmented expression of the anti-inflammatory cytokine IL-10. Additionally, testicular fibrosis markers including Masson's trichrome and transforming growth factor (TGF)-β expression were noticeably declined in LA-treated irradiated rats, together with the upregulation of peroxisome proliferator-activated receptor-ϒ expression. Collectively, LA ameliorates radiation-mediated spermatogenesis-defects and testicular-damage via suppression of oxidative stress/NF-ĸB/TGF-β signaling.
放射疗法是盆腔癌治疗中使用的主要方法之一。然而，睾丸功能障碍和不育是年轻成年癌症幸存者中最常见的副作用。临床上，α-硫辛酸（LA）已被用于改善精子质量，效果令人满意。因此，本研究调查了LA对睾丸损伤的辐射防护作用的潜在机制。将雄性Sprague-Dawley大鼠暴露于10 Gy的全身γ辐射，并在照射前一周和照射后三天给予LA（50 mg/kg，口服）。LA通过改善生精小管紊乱的组织学和超微结构变化，除了增加其直径、生精上皮厚度和约翰森评分外，还具有显著的保护睾丸组织免受辐射损伤的能力。辐射导致精子质量和数量显著下降，同时血清睾酮水平降低，而给予LA可维持精子发生。令人惊讶的是，LA通过恢复还原型谷胱甘肽水平和抗氧化酶活性（如过氧化氢酶和谷胱甘肽-S-转移酶），除了降低照射组睾丸中的丙二醛水平外，还表现出抗氧化特性。此外，LA通过下调核因子-κB（NF-κB）表达，随后降低白细胞介素（IL）-6和环氧合酶-2表达，同时增加抗炎细胞因子IL-10的表达，减轻睾丸炎症。此外，在LA处理的照射大鼠中，包括Masson三色染色和转化生长因子（TGF）-β表达在内的睾丸纤维化标志物明显下降，同时过氧化物酶体增殖物激活受体-γ表达上调。总之，LA通过抑制氧化应激/NF-κB/TGF-β信号通路改善辐射介导的精子发生缺陷和睾丸损伤。
