title: Pulmonary function changes in rats with taurocholate-induced pancreatitis are attenuated by pretreatment with melatonin.
abstract: Melatonin is a free radical scavenger and broad-spectrum antioxidant with immunomodulatory effects. We studied the effects of melatonin on changes in lung function, oxidative/nitrosative stress, and inflammatory cell sequestration in an acute pancreatitis (AP)-associated lung inflammation model. Acute pancreatitis was induced by injection of 5% sodium taurocholate into the pancreatic duct of rats. Animals were randomized into control, AP, and a melatonin pretreatment (10 mg/kg)/AP group. Functional residual capacity (FRC), lung compliance (Cchord), expiratory flow rate at 50% (FEF50), airway resistance index (RI), and peak expiratory flow rate (PEF) were evaluated. White blood cell count (WBC) and hydrogen peroxide, lung lavage fluid WBC, methylguanidine, protein, lactic dehydrogenase (LDH), nitric oxide (NO), and leukotriene B4 (LTB4) levels were determined. Lung wet-to-dry weight ratio, peroxynitrite, and inducible nitric oxide synthase (NOS) mRNA and protein were measured. AP induction resulted in reductions in FRC, Cchord, FEF50, and PEF, and increase in RI and lung wet-to-dry weight ratio. Blood and lung lavage fluid WBC, lavage fluid LDH, protein, and blood hydrogen peroxide also increased. Levels of hydroxyl radicals, nitric oxide, and LTB4 in lung lavage fluid, inducible NOS mRNA, protein expression, and peroxynitrite in lung tissue also were significantly elevated. Pretreatment with melatonin attenuated obstructive and restrictive ventilatory insufficiency induced by AP. Blood and lavage WBC, lavage LDH and protein, lung edema, oxidative/nitrosative stress, and lipoxygenase pathway derivatives were also significantly attenuated by melatonin. We conclude that melatonin decreases AP-induced obstructive and restrictive lung function changes via its antioxidant and anti-inflammatory properties.
authors: Medical Imaging Department, Cardinal Tien Hospital, New Taipei City, Taiwan; School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
authors: Ting-Ywan
authors: TY
authors: Chou
authors: Russel J
authors: RJ
authors: Reiter
authors: Kuan-Hao
authors: KH
authors: Chen
authors: Fur-Jiang
authors: FJ
authors: Leu
authors: David
authors: D
authors: Wang
authors: Diana Y
authors: DY
authors: Yeh
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D006861:Hydrogen Peroxide; D007962:Leukocytes; D008168:Lung / Q000187:drug effects*; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D012143:Respiratory Physiological Phenomena / Q000187:drug effects*; D013656:Taurocholic Acid / Q000009:adverse effects*
chemical_list: D000975:Antioxidants; D013656:Taurocholic Acid; D006861:Hydrogen Peroxide; D008550:Melatonin
keywords: lung function; melatonin; nitrosative stress; oxidative stress; pancreatitis