Antiinflammatory Effect of N-Acetylcysteine Combined with Exogenous Surfactant in Meconium-Induced Lung Injury.
Neonatal meconium aspiration syndrome (MAS) can be treated by exogenous surfactant (S). However, aspirated meconium initiates local inflammation and oxidation which may inactivate surfactant and reduce its action. This experimental study estimated whether combined use of surfactant and the antioxidant N-acetylcysteine (NAC) can enhance effectiveness of therapy. Meconium-instilled rabbits were non-treated (M), treated with monotherapies (M + S, M + NAC), combined therapy (M + S + NAC), or received saline instead of meconium (controls, C). Surfactant therapy consisted of two lung lavages (BAL) with diluted Curosurf (5 mg phospholipids/ml, 10 ml/kg) followed by undiluted Curosurf (100 mg phospholipids/kg). N-acetylcysteine (Acc Injekt, 10 mg/kg) was given intravenously in M + S + NAC group 10 min after surfactant therapy. Animals were oxygen-ventilated for additional 5 h. Then, differential white cell count in the blood (WBC) was determined. Left lung was saline-lavaged and differential cell count in BAL was determined. In right lung tissue, wet/dry weight ratio, oxidation markers (TBARS, 3NT) and interleukines (IL-2, IL-6, IL-13, and TNFα) using ELISA and RT-PCR were estimated. Combined S + NAC therapy significantly decreased W/D ratio, TBARS, 3NT, and IL, whereas the effect of monotherapies (either S or NAC) was less obvious. In conclusion, addition of NAC to surfactant treatment may enhance the therapeutic outcome in MAS.
Biomedical Center Martin, Division of Respirology and Department of Physiology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, 4C Mala Hora St, SK-03601, Martin, Slovakia.
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Mikolka
Biomedical Center Martin, Division of Respirology and Department of Physiology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, 4C Mala Hora St, SK-03601, Martin, Slovakia.
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Kopincova
Biomedical Center Martin, Division of Respirology and Department of Physiology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, 4C Mala Hora St, SK-03601, Martin, Slovakia.
L Tomcikova
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Mikusiakova
Biomedical Center Martin, Division of Respirology and Department of Physiology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, 4C Mala Hora St, SK-03601, Martin, Slovakia.
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Kosutova
Biomedical Center Martin, Division of Respirology and Department of Physiology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, 4C Mala Hora St, SK-03601, Martin, Slovakia.
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Calkovska
Biomedical Center Martin, Division of Respirology and Department of Physiology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, 4C Mala Hora St, SK-03601, Martin, Slovakia. mokra@jfmed.uniba.sk.
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Mokra
D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008471:Meconium Aspiration Syndrome / Q000188:drug therapy* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011663:Pulmonary Surfactants / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D011663:Pulmonary Surfactants; D000111:Acetylcysteine
Antioxidant; Inflammation; Meconium aspiration syndrome; N-Acetylcysteine; Oxidative damage; Surfactant