The role of glutathione-S-transferase polymorphisms on clinical outcome of ALI/ARDS patient treated with N-acetylcysteine

Respir Med. 2009 Mar;103(3):434-41. doi: 10.1016/j.rmed.2008.09.013. Epub 2008 Nov 7.

Abstract

Oxidative stress has a proven role in pathophysiology of acute respiratory distress syndrome. The antioxidant drugs, especially N-acetylcysteine (NAC) have been used for years to overcome oxidative stress effects in patients. In the present study we have investigated the effects of NAC treatment (IV NAC in 150mg/kg at the first day followed by 50mg/kg/day for three days) on 27 ICU patients with ALI/ARDS considering the glutathione-S-transferase genetic variations, as an important enzyme contributing in oxidative stress pathways. The results indicated that NAC improved oxygenation (increase in PaO(2)/FiO(2)) and decreased mortality rate in treated patients compared to control group (p<0.05). Evaluation of three isoforms of glutathione-S-transferase (GST M1, P1 and T1), in these patients have showed an association between GST M1 null, and GST M1 and T1 double null polymorphisms with increased mortality in control group, suggesting antioxidant therapy critical for this group of patients.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / administration & dosage*
  • Acetylcysteine / therapeutic use
  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / genetics
  • Acute Lung Injury / mortality
  • Adult
  • Antioxidants / administration & dosage*
  • Antioxidants / therapeutic use
  • Case-Control Studies
  • Chi-Square Distribution
  • Drug Administration Schedule
  • Female
  • Gene Frequency
  • Genotype
  • Glutathione Transferase / genetics*
  • Humans
  • Male
  • Middle Aged
  • Oxidative Stress
  • Polymorphism, Genetic*
  • Respiratory Distress Syndrome, Adult / drug therapy*
  • Respiratory Distress Syndrome, Adult / genetics
  • Respiratory Distress Syndrome, Adult / mortality
  • Single-Blind Method
  • Treatment Outcome

Substances

  • Antioxidants
  • Glutathione Transferase
  • Acetylcysteine