J Korean Med Sci.  2003 Oct;18(5):649-654. 10.3346/jkms.2003.18.5.649.

Effects of N-acetyl-L-cysteine and Glutathione on Antioxidant Status of Human Serum and 3T3 Fibroblasts

Affiliations
  • 1Department of Internal Medicine and Clinical Research Institute, Soonchunhyang University Cheonan Hospital, Cheonan, Korea. eylee@sch.ac.kr
  • 2Cell Biology Team, Korea Basic Science Institute, Daejeon, Korea.

Abstract

The effectiveness of several sulfhydryl compounds in the treatment of paraquat intoxication has been previously tested based on their antioxidant ability. However, practical guidelines for their clinical use remain to be determined. As a preliminary pharmacokinetic study on sulfhydryl compounds, we attempted to establish the optimal concentration of N-acetyl-L-cysteine, glutathione, superoxide dismutase, and catalase. We measured the antioxidant effect of these antioxidants in normal pooled plasma and on intracellular reactive oxygen species (ROS) induced by paraquat. N-acetyl-L-cysteine begins to suppress the production of ROS in plasma at concentrations as low as 5 mM, with the suppression being maximal at 40 mM. In the same way, glutathione increased the total antioxidant status in plasma at concentrations of 5-40 mM in a dose-dependent manner. Complete suppression of ROS in plasma induced by exposure to 500 micrometer paraquat for 40 min was observed when using 40 mM N-acetyl-L-cysteine and 5 mM glutathione. These concentrations are comparable with 50 units of catalase, which reduced ROS at concentrations of 5-100 units. Further pharmacokinetic study into the systemic administration of these antioxidants is necessary, using effective concentrations of 5-40 mM for both N-acetyl-L-cysteine and glutathione, and 1-50 units of catalase.

Keyword

Antioxidants; Glutathione; Acetylcysteine; Paraquat; Poisoning

MeSH Terms

Acetylcysteine/*pharmacology
Animals
Antioxidants/pharmacokinetics/*pharmacology
Ascorbic Acid/metabolism
Catalase/metabolism
Dose-Response Relationship, Drug
Free Radical Scavengers/pharmacology
Glutathione/metabolism/*pharmacology
Human
Mice
NIH 3T3 Cells
Paraquat/pharmacology
Reactive Oxygen Species
Serum/*drug effects
Support, Non-U.S. Gov't
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