N-acetylcysteine and Ambroxol Inhibit Endotoxin-induced Phagocyte Accumulation in Rat Lungs

We have investigated whether pretreatment with N-acetylcysteine (NAC) and/or ambroxol (Amb), drugs known as reactive oxygen species (ROS) scavengers, would minimize lipopolysaccharide (LPS)-induced leucocyte accumulation in rat lung microvasculature and protect lungs from damage and the effect of th...

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Published in:Pulmonary pharmacology & therapeutics 1999-12, Vol.12 (6), p.369-375
Main Authors: Nawrocka, A., Papierz, W., Bialasiewicz, P., Stolarek, R., Komos, J., Nowak, D.
Format: Article
Language:English
Subjects:
Acetylcysteine - pharmacology
Ambroxol - pharmacology
Animals
Endotoxins - pharmacology
Escherichia coli - metabolism
Expectorants - pharmacology
Humans
Lipopolysaccharide, Endotoxin, Phagocyte influx, N-acetylcysteine, Ambroxol, Lung damage
Lipopolysaccharides - pharmacology
Luminescent Measurements
Lung - cytology
Lung - drug effects
Macrophages, Alveolar - drug effects
Male
Neutrophils - drug effects
Phagocytes - drug effects
Pulmonary Alveoli - cytology
Pulmonary Alveoli - drug effects
Rats
Rats, Wistar
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Summary:We have investigated whether pretreatment with N-acetylcysteine (NAC) and/or ambroxol (Amb), drugs known as reactive oxygen species (ROS) scavengers, would minimize lipopolysaccharide (LPS)-induced leucocyte accumulation in rat lung microvasculature and protect lungs from damage and the effect of these drugs on chemotactic peptide (fMLP)-induced chemiluminescence of human polymorphonuclear leukocytes (PMNs). Animals were injected ip with NAC (27.6 mg/kg, n=8), ambroxol (70 mg/kg, n=8), combination NAC+ambroxol (n=8), or 1 ml buffer alone (n=8), once a day for 3 consecutive days. Then animals were injected with LPS (17 mg/kg), and killed 3 h later. In each of another four groups eight rats were used as a control, and received the same drug treatment but LPS was replaced with 0.9% NaCl. PMNs and macrophages (Ms) were counted in histologic slides of lung tissue. Using computer image analysis we measured the area of alveolar profiles. Luminol-enhanced chemiluminescence was measured in PMNs suspensions obtained from healthy volunteers. Chemiluminescence intensity was measured in resting and fMLP-stimulated cells, and compared between cells incubated with Amb, NAC or distilled water. We observed significant differences in the number of PMNs and Ms, alveolar profile area between control and LPS-treated animals (P
ISSN:1094-5539
1522-9629
DOI:10.1006/pupt.1999.0219