J Korean Med Sci.  2005 Oct;20(5):721-726. 10.3346/jkms.2005.20.5.721.

Pharmacokinetics of Glutathione and Its Metabolites in Normal Subjects

• Hong SY
• Gil HW
• Yang JO
• Lee EY
• Kim HK
• Kim SH
• Chung YH
• Hwang SK
• Lee ZW

• KMID: 1781751
• DOI: http://doi.org/10.3346/jkms.2005.20.5.721

Abstract

To determine the loading and maintenance dosage of glutathione (GSH) for patients suffering from reactive oxygen species (ROS) injury such as acute paraquat intoxication, a kinetic study of reduced GSH was performed in synchrony with that of cysteine (Cys), cystine (Cys2), and methionine (Met). Human subject's porticipitation was voluntary. The effective dose of Cys, Cys2, and Met against ROS in fibroblast cells generated by paraquat was assessed using laser scanning confocal microscopy. Both Cys and Met suppressed ROS in a dose-dependent manner at concentrations of 1-1,000 micrometer; the concentration required to suppress ROS by 50% was 10 micrometer for Cys and 50 micrometer for Met. Using metabolite kinetics with the assumption that Cys and Met are the metabolites of GSH, expected concentrations of Cys and Met of above 20 and 50 micrometer were estimated when GSH was administered at 50 mg/kg body weights every 205.4 min for Cys and 427.4 min for Met.

Keyword

Cysteine; Cystine; Glutathione; Methionine; Paraquat; Reactive Oxygen Species; Pharmacokinetics

MeSH Terms

Adult
Amino Acids/*blood
Animals
Dose-Response Relationship, Drug
Glutathione/administration and dosage/*blood/*pharmacokinetics
Humans
Kinetics
Male
Metabolic Clearance Rate/drug effects
Mice
Reactive Oxygen Species/*metabolism
Research Support, Non-U.S. Gov't
Swiss 3T3 Cells

Figure

• 

  Fig. 1 Effect of glutathione, cysteine and methinine on the production of ROS by paraquat in Swiss 3T3 fibroblasts. (A) 10 mM of GSH suppressed ROS in dose dependant pattern. Complete suppression of ROS was observed at 5 mM of GSH. (B) Cys at 1-1,000 µM suppressed the production of ROS in a dose-dependent manner. Software quantification of the signal intensities produced the following values: 2.50±0.31 in paraquat group, 2.25±0.22 in 1 µM Cys, 1.30±0.17 in 10 µM Cys, and 1.20±0.15 in 100 µM Cys. Complete suppression was observed at 1,000 µM Cys. (a) and (b) denote statistically significant differences in comparison with control (a) and (b) paraquat groups, respectively. (C) Met at 1-1,000 µM suppressed the production of ROS in a dose-dependent manner. Software quantification of the signal intensities produced the following values: 2.50±0.31 in paraquat group, 2.40±0.30 in 1 µM Met, 2.05±0.25 in 10 µM Met, 1.19±0.15 in 100 µM Met, and 1.05±0.12 in 1,000 µM Met. (a) and (b) denote statistically significant differences in comparison with control (a) and paraquat (b) groups, respectively.

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