Gheita Heba A, Shafey Ghada M, Aziz Maha M, Fadel Noha A
Drug Radiation Research Department, National Centre for Radiation Research and Technology, Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt.
BMC Complement Med Ther. 2025 Jun 9;25(1):211. doi: 10.1186/s12906-025-04950-7.
Radiation exposure of sensitive organs during radiotherapy merits extraordinary consideration, particularly when the concern is about fertility. Although alpha-tocopheryl (vitamin E) is a potent antioxidant, many studies have demonstrated the radioprotective impact of alpha-tocopheryl acetate ester, emphasizing its antioxidant and anti-apoptotic effects; fewer studies were conducted using the succinate ester without any declaration of its anti-inflammatory effect in the concerned pathology. Accordingly, the current study was conducted to evaluate the dual antioxidant and anti-inflammatory role of alpha-tocopheryl succinate (α-TCS) in reproductive toxicity induced by gamma-irradiation.
Animals were subjected to 6 Gy of whole-body gamma radiation and received α-TCS (200 mg/kg, P.O.) pre- and post-radiation. After the termination of the experiment, serum testosterone was estimated, and the testis weight was recorded. Besides, the testicular content of oxidative balance markers [malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT)] and inflammatory response markers [interleukin-1β (IL-1β), nuclear factor-kappa B (NF-κB) p65, peroxisome proliferator-activated receptor-γ (PPAR-γ)] were assessed.
Irradiated (IR) rats showed disturbances in the testicular function and abnormal incidental lesions, as demonstrated in the histopathological examinations. They exhibited marked alterations in the testicular oxidative balance, verified by the rise of lipid peroxidation end product (MDA) and depletion of antioxidant enzymes (CAT and SOD). Also, radiation exposure triggered an inflammatory response, which was evidenced by suppression of PPAR-γ and intensified expression of NF-κB p65 subunit, with subsequent elevation in IL-1β testicular content. Conversely, administering α-TCS to IR rats maintained the testicular architecture and ultrastructure while also preserving testicular function. Treatment with α-TCS restored the oxidative balance (MDA, SOD and CAT) and reduced testicular content of pro-inflammatory cytokine IL-1β via interference with the NF-κB p65/ PPAR-γ signaling pathway.
The current study sheds light on the crucial radioprotective role of α-TCS as a PPAR-γ agonist in maintaining testicular function partially through suppressing NF-κB activation and its downstream pro-inflammatory mediators.
放疗期间敏感器官的辐射暴露值得特别关注，尤其是当涉及生育能力时。尽管α-生育酚（维生素E）是一种有效的抗氧化剂，但许多研究已经证明了α-生育酚乙酸酯的辐射防护作用，强调了其抗氧化和抗凋亡作用；使用琥珀酸酯进行的研究较少，且未声明其在相关病理中的抗炎作用。因此，本研究旨在评估α-生育酚琥珀酸酯（α-TCS）在γ射线诱导的生殖毒性中的双重抗氧化和抗炎作用。
对动物进行6 Gy的全身γ辐射，并在辐射前后给予α-TCS（200 mg/kg，口服）。实验结束后，测定血清睾酮水平，并记录睾丸重量。此外，评估睾丸中氧化平衡标志物[丙二醛（MDA）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）]和炎症反应标志物[白细胞介素-1β（IL-1β）、核因子-κB（NF-κB）p65、过氧化物酶体增殖物激活受体-γ（PPAR-γ）]的含量。
组织病理学检查显示，受辐射（IR）大鼠的睾丸功能出现紊乱，伴有异常的偶然病变。它们的睾丸氧化平衡出现明显改变，脂质过氧化终产物（MDA）升高和抗氧化酶（CAT和SOD）减少证实了这一点。此外，辐射暴露引发了炎症反应，这通过PPAR-γ的抑制和NF-κB p65亚基表达的增强得以证明，随后睾丸中IL-1β含量升高。相反，给IR大鼠施用α-TCS可维持睾丸结构和超微结构，同时保留睾丸功能。α-TCS治疗通过干扰NF-κB p65/PPAR-γ信号通路恢复了氧化平衡（MDA、SOD和CAT），并降低了睾丸中促炎细胞因子IL-1β的含量。
本研究揭示了α-TCS作为PPAR-γ激动剂在维持睾丸功能方面的关键辐射防护作用，部分是通过抑制NF-κB激活及其下游促炎介质实现的。
