PMID- 12404881 OWN - NLM STAT- MEDLINE DCOM- 20021126 LR - 20151119 IS - 0004-4172 (Print) IS - 0004-4172 (Linking) VI - 52 IP - 9 DP - 2002 TI - Human neutrophil oxidative bursts and their in vitro modulation by different N-acetylcysteine concentrations. PG - 669-76 AB - 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. FAU - Allegra, Luigi AU - Allegra L AD - Department of Pharmacology, Institute of Respiratory Diseases, School of Medicine, University of Milan, Milan, Italy. FAU - Dal Sasso, Monica AU - Dal Sasso M FAU - Bovio, Cinzia AU - Bovio C FAU - Massoni, Carola AU - Massoni C FAU - Fonti, Elena AU - Fonti E FAU - Braga, Pier Carlo AU - Braga PC LA - eng PT - Journal Article PL - Germany TA - Arzneimittelforschung JT - Arzneimittel-Forschung JID - 0372660 RN - 0 (Free Radical Scavengers) RN - 0 (Oxidants) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - 5EXP385Q4F (Luminol) RN - 712K4CDC10 (Hypochlorous Acid) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 1.17.3.2 (Xanthine Oxidase) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetylcysteine/*pharmacology MH - Adult MH - Candida albicans/immunology MH - Cell-Free System MH - Dose-Response Relationship, Drug MH - Escherichia coli/immunology MH - Free Radical Scavengers/*pharmacology MH - Humans MH - Hydrogen Peroxide MH - Hypochlorous Acid MH - Immunity, Cellular/drug effects MH - Luminescent Measurements MH - Luminol MH - N-Formylmethionine Leucyl-Phenylalanine/pharmacology MH - Neutrophils/*drug effects MH - Oxidants MH - Phagocytosis/drug effects MH - Respiratory Burst/*drug effects MH - Staphylococcus aureus/immunology MH - Xanthine Oxidase/metabolism EDAT- 2002/10/31 04:00 MHDA- 2002/11/28 04:00 CRDT- 2002/10/31 04:00 PHST- 2002/10/31 04:00 [pubmed] PHST- 2002/11/28 04:00 [medline] PHST- 2002/10/31 04:00 [entrez] AID - 10.1055/s-0031-1299949 [doi] PST - ppublish SO - Arzneimittelforschung. 2002;52(9):669-76. doi: 10.1055/s-0031-1299949.