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Oral melatonin attenuates lung inflammation and airway hyperreactivity induced by inhalation of aerosolized pancreatic fluid in rats

Authors

  • Chao F. Chen,

    1. Division of Gastroenterology, Department of Internal Medicine, Cheng Hsin General Hospital and Department of Healthcare Information, School of Health, Ming Chuan University, Taoyuan County, Taiwan
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  • David Wang,

    1. Department of Medicine, College of Medicine, Fu Jen Catholic University, Taipei Hsien, Taiwan
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  • Russel J. Reiter,

    1. Department of Cellular and Structural Biology, Graduate School of Biomedical Sciences, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
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  • Diana Y. Yeh

    1. Department of Medicine, College of Medicine, Fu Jen Catholic University, Taipei Hsien, Taiwan
    2. Division of Chest Medicine, Department of Internal Medicine, Shin Kong Wu-Ho-Su Memorial Hospital, Taipei, Taiwan
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Address reprint requests to Diana Y. Yeh, Division of Chest Medicine, Department of Medicine, Shin Kong Memorial Hospital, 95 WenChang Rd., Taipei, Taiwan.
E-mail: dyyeh@yahoo.com

Abstract

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.

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