Department of Microbiology, Key Laboratory of Anti-inflammatory and Immunopharmacology in Anhui Province, Anhui Medical University, Hefei, China.
J Pineal Res. 2010 Mar;48(2):109-16. doi: 10.1111/j.1600-079X.2009.00733.x. Epub 2010 Jan 8.
Previous research has shown that antioxidant (butylated hydroxyanisole) treatment ameliorates respiratory syncytial virus (RSV)-induced disease and lung inflammation. Melatonin has been reported to exhibit a wide varieties of biological effects, including antioxidant and anti-inflammation, and has no evident toxicity and side effect. But it is not known whether melatonin would modify RSV-induced lung disease and oxidative stress. The present study was to establish the involvement of oxidative stress in the pathogenesis of RSV-induced lung inflammation, and to investigate the protective effect of administration of melatonin in mice with RSV-induced oxidative pulmonary injury for 4 days. Malondialdehyde (MDA), an end product of lipid peroxidation, and glutathione (GSH) and superoxide dismutase (SOD) and nitric oxide (NO) levels were evaluated in lung tissue homogenates by spectrophotometry. Hydroxyl radical (.-OH), one of the indicators of free radical formation, was also detected in lung homogenates by Fenton reaction. Tumor necrosis factor-a (TNF-a) concentrations in mouse serum were measured with ELISA assay. The results demonstrated that the mice intranasally inoculated with RSV resulted in oxidative stress changes by increasing NO, MDA and .-OH levels, and decreasing GSH and SOD activities, whereas administration of melatonin significantly reversed all these effects. Furthermore, melatonin inhibited production of proinflammatory cytokines such as TNF-a in serum of RSV-infected mice. These results suggest that melatonin ameliorates RSV-induced lung inflammatory injury in mice via inhibition of oxidative stress and proinflammatory cytokine production and may be as a novel therapeutic agent in virus-induced pulmonary infection.
先前的研究表明，抗氧化剂（丁羟甲苯）治疗可以改善呼吸道合胞病毒（RSV）引起的疾病和肺部炎症。褪黑素已被报道具有广泛的生物学效应，包括抗氧化和抗炎作用，且没有明显的毒性和副作用。但是，褪黑素是否会改变 RSV 引起的肺部疾病和氧化应激尚不清楚。本研究旨在建立氧化应激在 RSV 引起的肺部炎症发病机制中的作用，并研究褪黑素在 RSV 诱导的氧化肺损伤小鼠中 4 天给药的保护作用。通过分光光度法在肺组织匀浆中评估丙二醛（MDA），一种脂质过氧化的终产物，以及谷胱甘肽（GSH）、超氧化物歧化酶（SOD）和一氧化氮（NO）水平。通过 Fenton 反应还检测了肺匀浆中的羟自由基（.-OH），这是自由基形成的指标之一。通过 ELISA 测定法测定小鼠血清中的肿瘤坏死因子-α（TNF-α）浓度。结果表明，用 RSV 滴鼻感染的小鼠通过增加 NO、MDA 和.-OH 水平，以及降低 GSH 和 SOD 活性，导致氧化应激变化，而褪黑素的给药显著逆转了所有这些作用。此外，褪黑素抑制了 RSV 感染小鼠血清中促炎细胞因子如 TNF-α的产生。这些结果表明，褪黑素通过抑制氧化应激和促炎细胞因子的产生，改善了 RSV 诱导的小鼠肺部炎症损伤，可能是病毒引起的肺部感染的一种新型治疗剂。
