Human neutrophil oxidative bursts and their in vitro modulation by different N-acetylcysteine concentrations.
Reactive oxygen species released by activated polymorphonuclear leukocytes as an expression of their defensive function are considered to be a major source of the cytotoxic oxidant stress, that triggers a self-sustaining phlogogenic loop in the respiratory system. N-Acetylcysteine (CAS 616-91-1, NAC), a known mucolytic drug, possesses also antioxidant properties, but it undergoes a rapid and extensive first-pass metabolism resulting in low tissue availability. Thus to further improve the NAC bioavailability a single oral administration of 1200 mg NAC has been recently proposed. This study has been performed to investigate in vitro by means of luminol amplified chemiluminescence the ability of the concentration of 35 mumol/l NAC available after single oral administration of 1200 NAC to interfere with human neutrophil oxidative burst evoked by both corpuscolate and soluble stimulants, in comparison with 16 mumol/l NAC, the serum concentration obtainable after single oral administration of 600 mg NAC. At concentrations of 16 and 35 mumol/l, NAC significantly reduced in a concentration-dependent manner the activation of polymorphonuclear neutrophils (PMNs) oxidative bursts induced by all of the stimulants (C. albicans, formyl-methionyl-leucyl-phenylalanine (fMLP), phorbol myristate acetate (PMA)). This effect was also present in cell-free systems, thus confirming the scavenger activity of these two concentrations of NAC. The fact that no effects were seen on PMN phagocytosis and bacterial killing indicates that NAC has no negative influence on other PMN functions such as antimicrobial activity.
Allegra
Luigi
L
Department of Pharmacology, Institute of Respiratory Diseases, School of Medicine, University of Milan, Milan, Italy.
Dal Sasso
Monica
M
Bovio
Cinzia
C
Massoni
Carola
C
Fonti
Elena
E
Braga
Pier Carlo
PC
D000111:Acetylcysteine / Q000494:pharmacology*; D000328:Adult; D002176:Candida albicans / Q000276:immunology; D002474:Cell-Free System; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000276:immunology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide; D006997:Hypochlorous Acid; D007111:Immunity, Cellular / Q000187:drug effects; D008163:Luminescent Measurements; D008165:Luminol; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D016877:Oxidants; D010587:Phagocytosis / Q000187:drug effects; D016897:Respiratory Burst / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000276:immunology; D014969:Xanthine Oxidase / Q000378:metabolism
D016166:Free Radical Scavengers; D016877:Oxidants; D009240:N-Formylmethionine Leucyl-Phenylalanine; D008165:Luminol; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase; D000111:Acetylcysteine