The different aspects of the biological role of glutathione (IR90)[2007-07]

The different aspects of the biological role of glutathione (IR90)[2007-07]
Document Type: Research article

The different aspects of the biological role of glutathione (IR90)[2007-07]

http://www.ncbi.nlm.nih.gov/pubmed/17679914?ordinalpos=6&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

[The different aspects of the biological role of glutathione][Article in Polish]
Bilska A, Kryczyk A, Włodek L.
Katedra Biochemii Lekarskiej Uniwersytetu Jagiellońskiego Collegium Medicum w Krakowie.

Glutathione plays a key role in maintaining a physiological balance between prooxidants and antioxidants, crucial for the life and death of a cell. Glutathione occurs in the human body in several redox forms, of which reduced glutathione (GSH), oxidized glutathione (GSSG), S-nitrosoglutathione (GSNO), and mixed disulfides of glutathione with proteins are the most important. There is a clear relationship between the levels of different redox forms of glutathione and the regulation of cellular metabolism in a broad sense. Therefore, each of these forms of glutathione can be beneficial or harmful to the organism depending on the cell type and its metabolic status. In such a situation, elevation of GSH level can constitute a very important factor aiding treatment. A rise in GSH level is beneficial in all pathological states, accompanied by lowered GSH content, while a lowering of GSH level is an indication to induce short-term immunosuppression required in organ transplantation and in tumor cells to selectively increase their sensitivity to chemo- and radiotherapy. GSH itself cannot be used as a therapeutic since it is not transported through plasma membranes. Cysteine, an amino acid which limits glutathione biosynthesis, also cannot be used in therapy due to its high neurotoxicity. For this reason, there is currently an intensive search for possibilities of modulating cellular glutathione and cysteine levels, and this problem can be the subject of interdisciplinary studies combining such scientific fields as biology, pharmacology, toxicology, and clinical medicine.

PMID: 17679914 [PubMed - indexed for MEDLINE]

Treatment with glutathione precursor decreases cytokine activity [1999]

Treatment with glutathione precursor decreases cytokine activity [1999]

Journal of Parenteral and Enteral Nutrition, Vol. 23, No. 1, 1-6 (1999)
DOI: 10.1177/014860719902300101
© 1999 The American Society for Parenteral and Enteral Nutrition

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Clinical Trial

Treatment with glutathione precursor decreases cytokine activity
LR Pena, DB Hill and CJ McClain

BACKGROUND:

Inflammatory cytokine activity is increased in many forms of experimental and clinical liver injury including alcoholic liver disease (ALD). Monocytes and Kupffer cells produce cytokines such as tumor necrosis factor (TNF), interleukin (IL)-8, and IL-6 in response to stimuli such as endotoxin (lipopolysaccharide [LPS]). This cytokine production is regulated by the oxidative stress-sensitive transcription factor NFkappaB. Glutathione (GSH) prodrugs such as oxathizolidine-4-carboxylic acid (OTZ) can inhibit activation of NFkappaB and subsequent cytokine production in monocytes and Kupffer cells in vitro. The objective of this study was to treat stable cirrhotic patients with OTZ in vivo to evaluate its effects on monocyte cytokine production (TNF, IL-8, and IL-6) and whole blood GSH levels. METHODS: Nine patients with stable cirrhosis received OTZ (70 mg/kg IV every 8 hours) for 9 days. Peripheral blood monocytes were obtained on study days 1 and 9, using density gradient centrifugation and adherence to plastic, and were stimulated with LPS (5 microg/mL). TNF, IL-8, and IL-6 were measured in culture supernatants by enzyme-linked serum immunosorbent assay. Whole blood GSH levels were measured by high-performance liquid chromatography. RESULTS: There was a significant decrease in monocyte TNF, IL-8, and IL-6 production after OTZ therapy. Patients with cirrhosis had significantly lower admission whole blood GSH levels compared with controls and GSH normalized with OTZ administration.

CONCLUSIONS:

Treatment with the GSH prodrug OTZ inhibited monocyte cytokine production and increased whole blood GSH. This may have important therapeutic implications for multiple cytokine-mediated disease processes.