1. N-acetylcysteine effectively diminished meconium-induced oxidative stress in adult rabbits.
- Author
-
Mokra D, Drgova A, Mokry J, Antosova M, Durdik P, and Calkovska A
- Subjects
- Age Factors, Animals, Biomarkers metabolism, Disease Models, Animal, Humans, Infant, Newborn, Inflammation Mediators metabolism, Leukocytes drug effects, Leukocytes metabolism, Lipid Peroxidation drug effects, Lung immunology, Lung metabolism, Lung Injury chemically induced, Lung Injury immunology, Lung Injury metabolism, Meconium Aspiration Syndrome chemically induced, Meconium Aspiration Syndrome immunology, Meconium Aspiration Syndrome metabolism, Mitochondria drug effects, Mitochondria metabolism, Pneumonia chemically induced, Pneumonia immunology, Pneumonia metabolism, Pulmonary Edema metabolism, Pulmonary Edema prevention & control, Rabbits, Thiobarbituric Acid Reactive Substances metabolism, Time Factors, Acetylcysteine pharmacology, Antioxidants pharmacology, Lung drug effects, Lung Injury prevention & control, Meconium, Meconium Aspiration Syndrome prevention & control, Oxidative Stress drug effects, Pneumonia prevention & control
- 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.
- Published
- 2015