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: D Mokra, A Drgova, J Mokry, M Antosova, P Durdik, A Calkovska
• Journal: Journal of physiology and pharmacology : an official journal of the Polish Physiological Society (J Physiol Pharmacol) Vol. 66 Issue 1 Pg. 101-10 (Feb 2015) ISSN: 1899-1505 [Electronic] Poland
• PMID: 25716970 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Biomarkers
• Inflammation Mediators
• Thiobarbituric Acid Reactive Substances
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Age Factors
• Animals
• Antioxidants (pharmacology)
• Biomarkers (metabolism)
• Disease Models, Animal
• Humans
• Infant, Newborn
• Inflammation Mediators (metabolism)
• Leukocytes (drug effects, metabolism)
• Lipid Peroxidation (drug effects)
• Lung (drug effects, immunology, metabolism)
• Lung Injury (chemically induced, immunology, metabolism, prevention & control)
• Meconium
• Meconium Aspiration Syndrome (chemically induced, immunology, metabolism, prevention & control)
• Mitochondria (drug effects, metabolism)
• Oxidative Stress (drug effects)
• Pneumonia (chemically induced, immunology, metabolism, prevention & control)
• Pulmonary Edema (metabolism, prevention & control)
• Rabbits
• Thiobarbituric Acid Reactive Substances (metabolism)
• Time Factors