Qin Tao, Feng Danni, Zhou Bangyue, Bai Lirong, Yin Yinyan
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou University, Yangzhou 225009, China.
Antioxidants (Basel). 2022 Oct 11;11(10):2012. doi: 10.3390/antiox11102012.
Melatonin, an indoleamine synthesized in the pineal gland of mammals, is a natural bioactive compound with powerful antioxidant and anti-inflammatory properties. Here, we evaluated whether melatonin has the capacity to moderate the oxidative stress of dendritic cells (DCs) for inflammatory control in an acute lung injury (ALI) model. Our findings showed that melatonin remarkably inhibited total nitric oxide synthase (T-NOS) activity, nitric oxide (NO) production, intracellular reactive oxygen species (ROS) levels, and lipid peroxidation (MDA detection) levels in both an LPS-induced murine ALI model and LPS-induced DCs. Meanwhile, the reduced glutathione (GSH) level and the GSH/GSSG ratio were recovered. In addition, antioxidant enzymes, such as glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD), were increased in these processes. Moreover, melatonin also inhibited the LPS-induced secretions of IL-1β, IL-6, and TGF-β in vivo and in vitro. Finally, we found that the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) axis was required in the inhibition of LPS-induced oxidative stress in DCs by melatonin. Altogether, these data indicate that melatonin strongly suppresses the LPS-induced oxidative stress in DCs, which is a promising DC-targeted strategy via inflammatory control for ALI treatment.
褪黑素是一种在哺乳动物松果体中合成的吲哚胺，是一种具有强大抗氧化和抗炎特性的天然生物活性化合物。在此，我们评估了褪黑素是否有能力减轻树突状细胞（DCs）的氧化应激，以在急性肺损伤（ALI）模型中控制炎症。我们的研究结果表明，在脂多糖诱导的小鼠ALI模型和脂多糖诱导的DCs中，褪黑素均显著抑制总一氧化氮合酶（T-NOS）活性、一氧化氮（NO）生成、细胞内活性氧（ROS）水平和脂质过氧化（MDA检测）水平。同时，还原型谷胱甘肽（GSH）水平和GSH/GSSG比值得以恢复。此外，在这些过程中，抗氧化酶如谷胱甘肽过氧化物酶（GPx）、过氧化氢酶（CAT）和超氧化物歧化酶（SOD）增加。此外，褪黑素在体内和体外也抑制脂多糖诱导的IL-1β、IL-6和TGF-β分泌。最后，我们发现核因子红细胞2相关因子2（Nrf2）/血红素加氧酶1（HO-1）轴在褪黑素抑制脂多糖诱导的DCs氧化应激中是必需的。总之，这些数据表明褪黑素强烈抑制脂多糖诱导的DCs氧化应激，这是一种通过控制炎症治疗ALI的有前景的针对DCs的策略。
