Oral melatonin attenuates lung inflammation and airway hyperreactivity induced by inhalation of aerosolized pancreatic fluid in rats
Article first published online: 21 OCT 2010
© 2010 The Authors. Journal of Pineal Research © 2010 John Wiley & Sons A/S
Journal of Pineal Research
Volume 50, Issue 1, pages 46–53, January 2011
How to Cite
Chen, C. F., Wang, D., Reiter, R. J. and Yeh, D. Y. (2011), Oral melatonin attenuates lung inflammation and airway hyperreactivity induced by inhalation of aerosolized pancreatic fluid in rats. Journal of Pineal Research, 50: 46–53. doi: 10.1111/j.1600-079X.2010.00808.x
- Issue published online: 9 DEC 2010
- Article first published online: 21 OCT 2010
- Received May 23, 2010; accepted August 16, 2010.
- airway hyperreactivity;
- lung inflammation;
- nitrosative stress;
- oxidative stress;
- pancreatic fluid
Abstract: Melatonin is a free radical scavenger with potent antioxidant properties and immunomodulatory effects. The purpose of this study was to determine the effects of orally administered melatonin in a pancreatic fluid (PF)-induced lung inflammation and airway hyperreactivity model. Aerosolized PF was introduced into airways to induce inflammation in rats. Animals were randomized into three experimental groups: sham treated; PF treated (200 μL/kg); and PF with melatonin (10 mg/kg) pretreatment. Airway reactivity to methacholine, airflow and airway resistance, bronchoalveolar lavage (BAL) cellular differential, the tumor necrosis factor α (TNFα) level, lavage nitric oxide, hydroxyl radical, and lactic dehydrogenase (LDH) were compared among groups. mRNA expressions of inducible nitric oxide synthase (iNOS) and TNFα in lung tissues were determined by real-time polymerase chain reaction. Protein expressions of iNOS and nitrotyrosine and lung tissue myeloperoxidase (MPO) activity were determined using an ELISA assay. Oral melatonin treatment indicated anti-inflammatory efficacy as evidenced by decreased methacholine sensitivity by 24% and airway obstruction by 28%, reduction in BAL eosinophil (P < 0.01) and neutrophil counts (P < 0.05), LDH (P < 0.05), and TNFα concentrations (P < 0.05) when compared to levels in sham-treated rats. Melatonin-treated animals also had reduced nitric oxide and hydroxyl radical concentrations (P < 0.05) in lavage fluid. Oral melatonin significantly reduced mRNA and protein expression of iNOS (P < 0.05 and P < 0.01, respectively), TNFα (P < 0.05), nitrotyrosine (P < 0.05), and MPO activity (P < 0.05) in lung tissues when compared with the sham-treated animals. These results suggest that oral treatment with melatonin had a beneficial effect on PF-induced obstructive ventilatory insufficiency by attenuating nitrosative and oxidative stress.