Ionizing radiation interacts with the immune system and induces molecular damage in the cellular milieu by generating reactive oxygen species (ROS) leading to cell death. The present study was performed to investigate the protective efficacy of N-acetyl-L-tryptophan (NAT) against gamma-radiation-induced cell death in murine macrophage J774A.1 cells. The radioprotective efficacy of NAT was evaluated in terms of cell survivability, effect on antioxidant enzyme activity, and free radicals inhibition. Radioprotective efficacy of NAT pretreatment to irradiated cells was assessed via cell cycle progression, mitochondrial membrane potential (MMP) perturbation, and apoptosis regulation using flow cytometry. Results of the study demonstrated significant radioprotective efficacy (>80%) of NAT in irradiated cells as estimated by sulforhodamine B (SRB), MTT, and clonogenic assay. Significant (p < 0.001) reduction in ROS, xanthine oxidase, and mitochondrial superoxide levels along with increment in catalase, glutathione-s-transferase, glutathione, and ATPase activities in NAT pretreated plus irradiated cells was observed as compared to the gamma-irradiated cells. Further, significant (p < 0.001) stabilization of MMP and reduction in apoptosis was also observed in NAT pretreated plus irradiated cells as compared to irradiated cells that not pretreated with NAT. The current study demonstrates that NAT pretreatment to irradiated cells protects against gamma radiation-induced cell death by reducing oxidative stress, stabilizing MMP, and inhibiting apoptosis. These observations conclusively highlight the potential of developing NAT as a prospective radioprotective agent upon further validation using in-depth preclinical assessment in cellular and animal models.

中文翻译：

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N-乙酰-L-色氨酸 (NAT) 通过调节氧化还原稳态和线粒体功能障碍改善小鼠巨噬细胞 J774A.1 中辐射诱导的细胞死亡


电离辐射与免疫系统相互作用，并通过产生活性氧 (ROS) 导致细胞死亡，从而诱导细胞环境中的分子损伤。本研究旨在研究 N-乙酰基-L-色氨酸 (NAT) 对鼠巨噬细胞 J774A.1 细胞中伽马辐射诱导的细胞死亡的保护功效。从细胞存活率、对抗氧化酶活性的影响和自由基抑制方面评估了 NAT 的辐射防护功效。使用流式细胞术通过细胞周期进程、线粒体膜电位 (MMP) 扰动和细胞凋亡调节来评估 NAT 预处理对受辐射细胞的辐射防护功效。研究结果表明，通过磺胺罗丹明 B (SRB)、MTT 和克隆形成测定估计，NAT 对受辐射细胞具有显着的放射防护功效 (>80%)。与伽马射线照射的细胞相比，经 NAT 预处理和照射的细胞中，ROS、黄嘌呤氧化酶和线粒体超氧化物水平显着降低 ( p < 0.001)，同时过氧化氢酶、谷胱甘肽-s-转移酶、谷胱甘肽和 ATP 酶活性增加。此外，与未用 NAT 预处理的辐照细胞相比，在 NAT 预处理加辐照的细胞中也观察到 MMP 显着稳定 ( p < 0.001) 和细胞凋亡减少。目前的研究表明，对受辐射细胞进行 NAT 预处理可以通过减少氧化应激、稳定 MMP 和抑制细胞凋亡来防止伽马辐射诱导的细胞死亡。这些观察结果最终强调了在细胞和动物模型中使用深入的临床前评估进一步验证后开发 NAT 作为前瞻性放射防护剂的潜力。