title: N-acetylcysteine effectively diminished meconium-induced oxidative stress in adult rabbits.
abstract: Since inflammation and oxidative stress are fundamental in the pathophysiology of neonatal meconium aspiration syndrome (MAS), various anti-inflammatory drugs have been used in experimental and clinical studies on MAS. This pilot study evaluated therapeutic potential of N-acetylcysteine in modulation of meconium-induced inflammation and oxidative lung injury. Oxygen-ventilated adult rabbits were intratracheally given 4 ml/kg of meconium (25 mg/ml) or saline (Sal, n = 6). Thirty minutes later, meconium-instilled animals were treated with intravenous N-acetylcysteine (10 mg/kg, Mec + NAC, n=6) or were non-treated (Mec, n = 6). All animals were oxygen-ventilated for additional 5 hours. Total and differential blood leukocyte counts were determined at baseline, and at 1, 3 and 5 h of the treatment. After sacrificing animals, left lung was saline-lavaged and total and differential cell counts in the bronchoalveolar lavage fluid were determined. Right lung was used for biochemical analyses and for estimation of wet-dry weight ratio. In lung tissue homogenate, thiobarbituric acid-reactive substances (TBARS), dityrosine, lysine-lipid peroxidation (LPO) products, and total antioxidant status (TAS) were detected. In isolated lung mitochondria, TBARS, dityrosine, lysine-LPO products, thiol group content, conjugated dienes, and activity of cytochrome c oxidase were estimated. To evaluate systemic effects of meconium instillation and NAC treatment, TBARS and TAS were determined also in plasma. To evaluate participation of eosinophils in the meconium-induced inflammation, eosinophil cationic protein (ECP) was detected in plasma and lung homogenate. Meconium instillation increased oxidation markers and ECP in the lung and decreased TAS (all P<0.05). NAC treatment reduced ECP and oxidation markers (all P<0.05, except of dityrosine in homogenate and conjugated dienes in mitochondria) and prevented a decrease in TAS (P<0.01) in lung homogenate compared to Mec group. In plasma, NAC decreased TBARS (P<0.001) and ECP, and increased TAS (both P<0.05) compared to Mec group. Concluding, N-acetylcysteine diminished meconium-induced inflammation and oxidative lung injury.
authors.affiliation: Department of Physiology, Comenius University in Bratislava, Jessenius School of Medicine in Martin, Martin, Slovakia. mokra@jfmed.uniba.sk.
authors.forename: D
authors.initials: D
authors.lastname: Mokra
authors.forename: A
authors.initials: A
authors.lastname: Drgova
authors.forename: J
authors.initials: J
authors.lastname: Mokry
authors.forename: M
authors.initials: M
authors.lastname: Antosova
authors.forename: P
authors.initials: P
authors.lastname: Durdik
authors.forename: A
authors.initials: A
authors.lastname: Calkovska
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000367:Age Factors; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D055370:Lung Injury / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D008470:Meconium; D008471:Meconium Aspiration Syndrome / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D011654:Pulmonary Edema / Q000378:metabolism / Q000517:prevention & control; D011817:Rabbits; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D018836:Inflammation Mediators; D017392:Thiobarbituric Acid Reactive Substances; D000111:Acetylcysteine