Inhibitory effect of melatonin on lung oxidative stress induced by respiratory syncytial virus infection in mice

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Butylated Hydroxyanisole / pharmacology
  • Female
  • Hydroxyl Radical / metabolism
  • Lung / drug effects
  • Lung / metabolism*
  • Malondialdehyde / metabolism
  • Melatonin / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects*
  • Respiratory Syncytial Virus Infections / physiopathology*
  • Tumor Necrosis Factor-alpha / metabolism


  • Tumor Necrosis Factor-alpha
  • Butylated Hydroxyanisole
  • Nitric Oxide
  • Hydroxyl Radical
  • Malondialdehyde
  • Melatonin