Oxidant-antioxidant balance in granulocytes during ARDS. Effect of N-acetylcysteine

Details

Serval ID
serval:BIB_EF3BFEE158CA
Type
Article: article from journal or magazin.
Collection
Publications
Title
Oxidant-antioxidant balance in granulocytes during ARDS. Effect of N-acetylcysteine
Journal
Chest
Author(s)
Laurent  T., Markert  M., Feihl  F., Schaller  M. D., Perret  C.
ISSN
0012-3692 (Print)
Publication state
Published
Issued date
01/1996
Volume
109
Number
1
Pages
163-6
Notes
Clinical Trial
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't --- Old month value: Jan
Abstract
The production of cytotoxic oxygen radicals by activated granulocytes is a proposed mechanism of lung injury in ARDS. Protective effects of N-acetylcysteine (NAC) have been described in experimental and clinical ARDS. NAC could act in part by replenishing the intracellular stores of glutathione (GSH) in activated granulocytes, leading to detoxification of oxygen radicals produced by these cells. To test this hypothesis, 16 patients in the early phase of ARDS were randomized to receive either NAC (n = 8) or placebo (n = 8); granulocyte GSH, granulocyte oxygen radical production, and plasma levels of granulocyte elastase were measured in blood samples drawn sequentially within 8 h after the onset of ARDS (day 0), and then 24 (day 1), 72 (day 3), and 120 h (day 5) after the first sample; treatment with NAC or placebo was started immediately after day 0 and stopped just after day 3. Granulocyte GSH was significantly higher on days 1 and 3 when NAC was received by the patient. Unstimulated oxygen radical production, as measured ex vivo by luminol- and lucigenin-amplified chemiluminescence (CL), was higher in granulocytes from ARDS patients than from healthy control subjects, but was not influenced by NAC. The plasma levels of granulocyte elastase were five to eight times above the upper normal limit on day 0, decreased steadily until day 5, and were uninfluenced by NAC. In summary, parenteral NAC treatment started within 8 h of diagnosis increases the intracellular GSH in the granulocytes of ARDS patients without decreasing spontaneous oxidant production by these cells. The mechanisms of the protective effects of this drug previously reported in experimental and clinical ARDS remain to be established.
Keywords
Acetylcysteine/administration & dosage/*therapeutic use Acridines/diagnostic use Antioxidants/*metabolism Chemiluminescent Measurements Double-Blind Method Female Glutathione/metabolism Granulocytes/drug effects/enzymology/*metabolism Humans Indicators and Reagents Infusions, Intravenous Leukocyte Elastase Luminol/diagnostic use Male Middle Aged Oxidants/*metabolism Pancreatic Elastase/blood Placebos Reactive Oxygen Species/metabolism Respiratory Distress Syndrome, Adult/*drug therapy/*metabolism
Pubmed
Web of science
Create date
25/01/2008 9:38
Last modification date
20/08/2019 16:16
Usage data