title: Effects of surfactant/budesonide therapy on oxidative modifications in the lung in experimental meconium-induced lung injury.
abstract: Meconium aspiration syndrome (MAS) is a serious condition, which can be treated with exogenous surfactant and mechanical ventilation. However, meconium-induced inflammation, lung edema and oxidative damage may inactivate delivered surfactant and thereby reduce effectiveness of the therapy. As we presumed that addition of anti-inflammatory agent into the surfactant may alleviate inflammation and enhance efficiency of the therapy, this study was performed to evaluate effects of surfactant therapy enriched with budesonide versus surfactant-only therapy on markers of oxidative stress in experimental model of MAS. Meconium suspension (25 mg/ml, 4 ml/kg) was instilled into the trachea of young rabbits, whereas one group of animals received saline instead of meconium (C group, n = 6). In meconium-instilled animals, respiratory failure developed within 30 min. Then, meconium-instilled animals were divided into 3 groups according to therapy (n = 6 each): with surfactant therapy (M + S group), with surfactant + budesonide therapy (M + S + B), and without therapy (M group). Surfactant therapy consisted of two bronchoalveolar lavages (BAL) with diluted surfactant (Curosurf, 5 mg phospholipids/ml, 10 ml/kg) followed by undiluted surfactant (100 mg phospholipids/kg), which was in M + S + B group enriched with budesonide (Pulmicort, 0.5 mg/ml). Animals were oxygen-ventilated for additional 5 hours. At the end of experiment, blood sample was taken for differential white blood cell (WBC) count. After euthanizing animals, left lung was saline-lavaged and cell differential in BAL was determined. Oxidative damage, i.e. oxidation of lipids (thiobarbituric acid reactive substance (TBARS) and conjugated dienes) and proteins (dityrosine and lysine-lipoperoxidation products) was estimated in lung homogenate and isolated mitochondria. Total antioxidant capacity was evaluated in lung homogenate and plasma. Meconium instillation increased transmigration of neutrophils and production of free radicals compared to controls (P < 0.05). Surfactant therapy, but particularly combined surfactant + budesonide therapy reduced markers of oxidative stress versus untreated animals (P < 0.05). In conclusion, budesonide added into surfactant enhanced effect of therapy on oxidative damage of the lung.
authors.affiliation: Biomedical Center (BioMed) Martin, Division of Respirology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
authors.forename: P
authors.initials: P
authors.lastname: Mikolka
authors.affiliation: Biomedical Center (BioMed) Martin, Division of Respirology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.|Department of Physiology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
authors.forename: J
authors.initials: J
authors.lastname: Kopincova
authors.affiliation: Biomedical Center (BioMed) Martin, Division of Respirology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
authors.forename: L
authors.initials: L
authors.lastname: Tomcikova Mikusiakova
authors.affiliation: Biomedical Center (BioMed) Martin, Division of Respirology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
authors.forename: P
authors.initials: P
authors.lastname: Kosutova
authors.affiliation: Biomedical Center (BioMed) Martin, Division of Respirology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
authors.forename: M
authors.initials: M
authors.lastname: Antosova
authors.affiliation: Biomedical Center (BioMed) Martin, Division of Respirology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.|Department of Physiology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
authors.forename: A
authors.initials: A
authors.lastname: Calkovska
authors.affiliation: Biomedical Center (BioMed) Martin, Division of Respirology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia. mokra@jfmed.uniba.sk.|Department of Physiology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
authors.forename: D
authors.initials: D
authors.lastname: Mokra
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D019819:Budesonide / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D055370:Lung Injury / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008470:Meconium / Q000378:metabolism*; D008471:Meconium Aspiration Syndrome / Q000188:drug therapy*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011654:Pulmonary Edema / Q000188:drug therapy / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D011817:Rabbits; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D005609:Free Radicals; D011663:Pulmonary Surfactants; D019819:Budesonide