The administration of N-acetylcysteine reduces oxidative stress and regulates glutathione metabolism in the blood cells of workers exposed to lead

Clin Toxicol (Phila). 2013 Jul;51(6):480-6. doi: 10.3109/15563650.2013.802797. Epub 2013 Jun 4.


Context and objective: The aim of the study was to investigate whether treatment with N-acetylcysteine (NAC) is able to restore erythrocyte glutathione (GSH) content in workers exposed to lead. Additionally, we measured the leukocyte and erythrocyte activities of GSH-related enzymes, such as glutathione reductase (GR), glutathione-S-transferase (GST), and glucose-6-phosphate dehydrogenase (G6PD), and estimated the influence of NAC administration on oxidative stress intensity, which was measured as the lipofuscin (LPS) level in erythrocytes.

Methods: The exposed population consisted of 171 healthy males randomly divided into four groups. Workers in the first group (n = 49) were not administered any antioxidants, drugs, vitamins, or dietary supplements, while workers in the remaining groups were treated with NAC at three doses for 12 weeks (1 × 200 mg per day, 2 × 200 mg per day, and 2 × 400 mg per day). All workers continued to work during the study. The blood of all examined workers was drawn two times: at the beginning of the study and after 12 weeks of treatment.

Results and conclusion: Blood lead levels decreased significantly in all groups receiving NAC compared to those in baseline. Erythrocyte GSH concentrations were significantly elevated in workers receiving 400 and 800 mg of NAC compared to those in baseline by 5% and 6%, respectively. Erythrocyte G6PD activity was significantly elevated in workers receiving 200, 400, and 800 mg of NAC compared to those in baseline by 24%, 14%, and 14%, respectively. By contrast, there were no significant differences in leukocyte G6PD or leukocyte and erythrocyte glutathione reductase (GR) activities before and after treatment. Leukocyte GST activities decreased significantly after treatment in workers receiving 200 mg of NAC by 34%, while LPS levels decreased significantly in workers receiving 200, 400, and 800 mg of NAC compared to those in baseline by 5%, 15%, and 13%, respectively. In conclusion, NAC decreases oxidative stress in workers exposed to lead via stimulating GSH synthesis.

Publication types

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

MeSH terms

  • Acetylcysteine / therapeutic use*
  • Adult
  • Antioxidants / therapeutic use*
  • Erythrocytes / drug effects*
  • Erythrocytes / metabolism
  • Glucosephosphate Dehydrogenase / drug effects
  • Glucosephosphate Dehydrogenase / metabolism
  • Glutathione / metabolism*
  • Glutathione Reductase / drug effects
  • Glutathione Reductase / metabolism
  • Glutathione Transferase / drug effects
  • Glutathione Transferase / metabolism
  • Humans
  • Lead / blood
  • Lead Poisoning / blood
  • Lead Poisoning / drug therapy*
  • Lead Poisoning / metabolism
  • Male
  • Middle Aged
  • Occupational Exposure*
  • Oxidative Stress / drug effects*
  • Young Adult


  • Antioxidants
  • Lead
  • Glucosephosphate Dehydrogenase
  • Glutathione Reductase
  • Glutathione Transferase
  • Glutathione
  • Acetylcysteine