Improvement by N-acetylcysteine of acute respiratory distress syndrome through increasing intracellular glutathione,and extracellular thiol molecules and anti-oxidant power: evidence for underlying toxicological mechanisms
Free accessResearch articleFirst published online September, 2007
Improvement by N-acetylcysteine of acute respiratory distress syndrome through increasing intracellular glutathione,and extracellular thiol molecules and anti-oxidant power: evidence for underlying toxicological mechanisms
In acute respiratory distress syndrome (ARDS), there is extensive overproduction of free radicals to the extent that endogenous anti-oxidants are overwhelmed, permitting oxidative cell damage. The present study examined the benefit of the anti-oxidant compound N-acetylcysteine (NAC) in the management of ARDS by measuring patient's intracellular glutathione (inside red blood cells) and extracellular (plasma) anti-oxidant defense biomarkers and outcome. Twenty-seven ARDS patients were recruited from the intensive care unit of a teaching Hospital and randomly divided into two groups. Both groups were managed similarly by regular treatments but 17 patients received NAC 150 mg/kg at the first day that followed by 50 mg/kg/day for three days and 10 patients did not receive NAC. Treatment by NAC increased extracellular total anti-oxidant power and total thiol molecules and also improved intracellular glutathione and the outcome of the patients. In conclusion, patients with ARDS are in a deficient oxidant—anti-oxidant balance that can get a significant benefit if supplemented with NAC. Human & Experimental Toxicology (2007) 26,697—703
Levy B. , Shapiro SDAcute respiratory distress syndrome, In Kasper DL , et al. Harrison's Principle of International Medicine, sixteenth edition. McGraw Hill Medical , 2005: 1592—5.
2.
Vazin A. , Mojtahedzadeh M. , Salehifar E. , Rastkari N. , Khalaj S. , Rezaie A. , Abdollahi M.Future drugs for treatment of acute respiratory distress syndrome. IntlJ Pharmacol2005; 1: 9—16 .
3.
Summer WRRespiratory failure, In Goldman L, Bennett JC, Cecil's Textbook of Medicine, twentyfirst edition. W.B. Saunders Company , 2000: 468—9.
4.
Ware LB , Matthay MAMedical progress: the acute respiratory distress syndrome . N Engl J Med2000; 342: 1334—49 .
5.
Artigas A. , Bernard GR , Carlet J. , Dreyfuss D. et al. The American-European consensus conference on ARDS, part 2. ventilatory, pharmacologic, supportive therapy, study design strategies, and issues related to recovery and remodeling . Am J Respir Crit Care Med1998; 157: 1332—47 .
6.
Brower RG , Ware LB , Berthiaume Y. , Matthay MATreatment of ARDS . Chest2001; 120: 1347—67 .
7.
Lee WL , Downey GPNeutrophil activation and acute lung injury . Curr Opin Crit Care2001; 7: 1—7 .
8.
Behr J. , Maier K. , Krombach F. , Adelmann-Grill BCPathogenetic significance of reactive oxygen species in diffuse fibrosingalveolitis . Am Rev Respir Dis1991; 144: 146—50 .
9.
Salari P. , Mojtahedzadeh M. , Abdollahi M.Influence of serum epidermal growth factor on mechanical ventilation and survival in patients with acute respiratory distress syndrome . Therapy2005; 2: 393—8 .
10.
Cantin AM , Hubbard RC , Crystal RGGlutathione deficiency in the epithelial lining fluid of the lower respiratory tract in idiopathic pulmonary fibrosis . Am Rev Respir Dis1989; 139: 370—2 .
11.
Sznajder JI , Fraiman A. , Hall JB , Sanders W. , Schmidt G. , Crawford G. , Nahum A. , Factor P. , Wood LDIncreased hydrogen peroxide in the expired breath of patients with acute hypoxemic respiratory failure . Chest1989; 96: 606—12 .
12.
Baldwin SR , Simon RH , Grum CM , Ketai LH , Boxer LA , Devall LJOxidant activity in expired breath of patients with adult respiratory distress syndrome . Lancet1986; 1: 11—4 .
13.
Abdollahi M. , Ranjbar A. , Shadina S. , Nikfar S. , Rezaie A.Pesticides and oxidative stress: a review . Med Sci Monit2004; 10: RA144—RA147 .
14.
MacNee W. , Rahman I.Oxidants/antioxidants in idiopathic pulmonary fibrosis . Thorax1995; 1: S53—8 .
15.
Strausz J. , Muller-Quernheim J. , Steppling H. , Ferlinz R.Oxygen radical production by alveolar inflammatory cells in idiopathic pulmonary fibrosis . Am Rev Respir Dis1990; 141: 124—8 .
16.
Chow CW , Herrera Abreu MT , Suzuki T. , Downey GPOxidative stress and acute lung injury . Am J Respir Cell Mol Biol2003; 29: 427—31 .
17.
Gillissen A. , Nowak D.Characterization of N-acetylcysteine and ambroxol in anti-oxidant therapy . Respir Med1998; 92: 609—23 .
18.
Parris M. , Kidd, Ph.D.Glutathione-systemic protectant against oxidative and free radical damage . Alt Med Rev1997; 2: 155—76 .
19.
Kaur P. , Aschner M. , Syversen T.Role of glutathione in determining the differential sensitivity between the cortical and cerebellar regions towards mercury-induced oxidative stress . Toxicology2007; 230: 164—77 .
20.
Murray RKRed and white blood cells, In Murray RK , Granner DK et al., eds Harper's Biochemistry, twenty fourth editionAppleton and Lange , 1996: 736—37.
21.
Alonso de Vega JM , Diaz J. , Serrano E. , Carbonell LFOxidative stress in critically ill patients with systemic inflammatory response syndrome . Crit Care Med2002; 30: 1782—6 .
22.
Tsai K. , Hsu T. , Kong C. , Lin K. , Lu F.Is the endogenous peroxyl-radical scavenging capacity of plasma protective in systemic inflammatory disorders in humans?Free Radic Biol Med2000; 28: 926—33 .
23.
Pacht ER , Timerman AP , Lykens MG , Merola AJDeficiency of alveolar fluid glutathione in patients with sepsis and the adult respiratory distress syndrome . Chest1991; 100: 1397—403 .
24.
Bunnell E. , Pacht EROxidized glutathione is increased in the alveolar fluid of patients with the adult respiratory distress syndrome . Am Rev Respir Dis1993; 148: 1174—8 .
25.
Benrahmoune M. , Therond P. , Abedinzadeh Z.The reaction of superoxide radical with N-acetylcysteine . Free Radic Biol Med2000; 8: 775—82 .
26.
Aruoma OI , Halliwell B. , Hoey BM , Butler J.The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid . Free Radic Biol Med1989; 6: 593—7 .
27.
Buhl R. , Vogelmeier C. , Critenden M. , Hubbard RC , Hoyt RF Jr , Wilson EM , Cantin AM , Crystal RGAugmentation of glutathione in the fluid lining the epithelium of the lower respiratory tract by directly administering glutathione aerosol . Proc Natl Acad Sci USA1990; 87: 4063—7 .
28.
Meister A.Glutathione deficiency produced by inhibition of its synthesis, and its reversal; applications in research and therapy . Pharmacol Ther1991; 51: 155—94 .
29.
Meyer A. , Buhl R. , Magnussen H.The effect of oral N-acetylcysteine on lung glutathione levels in idiopathic pulmonary fibrosis . Eur Respir J1994; 7: 431—6 .
30.
Shadnia S. , Dasgar M. , Taghikhani S. , Mohammadirad A. , Khorasani R. , Abdollahi M.Protective effects of alpha-tocopherol and N-acetyl-cysteine on diazinon-induced oxidative stress and acetylcholinesterase inhibition in rats . Toxicol Mech Methods2007; 17: 109—15 .
31.
Meyer A. , Buhl R. , Kampf S. , Magnussen H.Intravenous N-acetylcysteine and lung glutathione of patients with pulmonary fibrosis and normals . Am J Respir Crit Care Med1995; 152: 1055—60 .
32.
Knaus WA , Draper EA , Wagner DP , Zimmerman JEAPACHE II: a severity of disease classification system . Crit Care Med1985; 13: 818—29 .
33.
Tietze F.Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues . Anal Biochem1969; 27: 502—22 .
34.
Iris F. , Benzie IF , Strain S.Reducing antioxidant assay . Methods Enzymol1999; 292: 15—27 .
35.
Hu MLMeasurement of protein thiol groups and glutathione in plasma . Methods Enzymol1994; 233: 380—5 .
36.
De Flora S. , Balansky R. et al. Mechanisms of carcinogenesis: the example of N-acetylecysteine. In: Ioannides C , Lewis DFV (eds). Drugs, diet and diseases, vol. 1. mechanistic approaches to cancer. Ellis Horwood , Hemel Hempstead , 1995: 151—203.
37.
Meister A.Metabolism and function of glutathione. In Dolphin D , Poulson R , Avramovis O eds. Glutathione: chemical, biochemical and medical aspects. John Wiley , 1989 : 367—74.
38.
Macedo E. , Abdulkader R. , Castro I. , Sobrinho AC , Yu L. , Vieira JM Jr.Lack of protection of N-acetylcysteine (NAC) in acute renal failure related to elective aortic aneurysm repair-a randomized controlled trial . Nephrol Dial Transplant2006; 21: 1863—9 .
39.
Han D. , Sen CK , Roy S. , Kobayashi MS , Tritschler HJ , Packer L.Protection against glutamate-induced cytotoxicity in C6 glial cells by thiol antioxidants . Am J Physiol1997; 273: R1771—8 .
40.
Bridgman Mme , Marsden M. , MacNee W, Flenley DC, Ryle AP. Cysteine and glutathione concentrations in plasma and bronchoalveolar lavage fluid after treatment with NAC . Thorax1991; 46: 39—42 .
41.
Staal FJ , Ela SW , Roederer M. , Anderson MT , Herzenberg LA , Herzenberg LAGlutathione deficiency and human immunodeficiency virus infection . Lancet1992; 339: 909—12 .
42.
Paterson RL , Galley HF , Webster NRThe effect of N-acetylcysteine on nuclear factor-kappa B activation, interleukin-6, interleukin-8, and intercellular adhesion molecule-1 expression in patients with sepsis . Crit Care Med2003; 31: 2574—8 .
43.
Koksel O. , Ozdulger A. , Ercil M. , Tamer L. , Ercan B. , Atik U. , Cinel L. , Cinel I. , Kanik A.Effects of N-acetylcysteine on oxidant-antioxidant balance in oleic acid-induced lung injury . Exp Lung Res2004; 30: 431—46 .
44.
Kajbaf F. , Mojtahedzadeh M. , Abdollahi M.Mechanisms underlying stress-induced hyperglycemia in critically ill patients . Therapy2007; 4(1): 97—106 .
