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Oral melatonin attenuates lung inflammation and airway hyperreactivity induced by inhalation of aerosolized pancreatic fluid in rats
Author(s) -
Chen Chao F.,
Wang David,
Reiter Russel J.,
Yeh Diana Y.
Publication year - 2011
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2010.00808.x
Subject(s) - melatonin , bronchoalveolar lavage , methacholine , nitric oxide , nitric oxide synthase , medicine , endocrinology , nitrotyrosine , myeloperoxidase , inhalation , inflammation , eosinophil , lung , airway resistance , pharmacology , chemistry , immunology , respiratory disease , anesthesia , asthma
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.