Hostname: page-component-77c89778f8-m42fx Total loading time: 0 Render date: 2024-07-21T00:46:45.386Z Has data issue: false hasContentIssue false

Glutathione status in critically-ill patients: possibility of modulation by antioxidants

Published online by Cambridge University Press:  28 February 2007

Jan Wernerman*
Affiliation:
Department of Anaesthesia and Intensive Care and Unit of Anaesthesiologic Metabolism at KFC, Huddinge Hospital, Department of Surgery, St Görans Hospital, Karolinska Institutet, S-141 86 Huddinge, Stockholm, Sweden
Jia-Li Luo
Affiliation:
Department of Anaesthesia and Intensive Care and Unit of Anaesthesiologic Metabolism at KFC, Huddinge Hospital, Department of Surgery, St Görans Hospital, Karolinska Institutet, S-141 86 Huddinge, Stockholm, Sweden
Folke Hammarqvist
Affiliation:
Department of Anaesthesia and Intensive Care and Unit of Anaesthesiologic Metabolism at KFC, Huddinge Hospital, Department of Surgery, St Görans Hospital, Karolinska Institutet, S-141 86 Huddinge, Stockholm, Sweden
*
*Corresponding Author: Professor Jan Wernerman, fax +46 87795424, email Jan.Wernerman@anaesth.hs.sll.se
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Muscle tissue serves as a protein reservoir which is mobilized to meet the specific metabolic needs associated with various catabolic conditions in human subjects, such as trauma and critical illness. Glutathione is one of the most abundant short-chain peptides and a major source of non-protein thiol in the body, and tissue glutathione concentration is related to its oxidative capacity. Skeletal muscle is relatively unique with respect to a variety of metabolic properties, such as oxidative potential, patterns of amino acid utilization, and antioxidant enzyme activity. The glutathione concentration is not influenced by food intake, or by food deprivation. Moreover, there is no diurnal variation on muscle glutathione levels. Following elective surgery the muscle concentration of GSH (the reduced form) decreases by 40 % 24 h post-operatively, while the concentration of GSSG (the oxidized form) remains unaltered. During critical illness a similar decrease in the GSH concentration is seen, but in addition a change in the redox status indicative of an elevated GSSG level occurs. Furthermore, correlations between the concentrations of glutamine as well as glutamate and GSH exist in these patients. From available evidence accumulated it is clear that glutathione plays a pivotal role in the maintenance of the intracellular redox status, the antioxidant vitamin levels, and the antioxidant enzyme functions under various metabolic conditions. The effectiveness of glutathione protection in the individual tissue depends on the tissue concentration of glutathione as well as the capacity of the tissue to import GSH and to export GSSG. The mechanisms by which catabolism regulates tissue glutathione levels and the enzyme activities associated with the γ-glutamyl cycle are not completely understood and further studies need to be conducted.

Type
Clinical Nutrition and Metabolism Group Symposium on ‘Nutrition and antioxidants’
Copyright
Copyright © The Nutrition Society 1999

References

Adams, JD, Lauterburg BH & Mitchell, JR (1983) Plasma glutathione and glutathione disulfide in the rat: regulation and response to oxidative stress. Journal of Pharmacology and Experimental Therapeutics 227, 749754.Google ScholarPubMed
Akerboom, TP & Sies, H (1994) Transport of glutathione disulfide and glutathione mixed disulfides in biological samples. Methods in Enzymology 77, 373382.CrossRefGoogle Scholar
Andersson, K, Luo, J-L, Hammarqvist, F & Werner-man, J (1994) The effect of fasting on muscle glutathione and amino acid levels. Clinical Nutrition 13, Suppl., 45.CrossRefGoogle Scholar
Cook, ND & Peters, TJ (1986) The simultaneous hydrolysis of glutathione and glutamine by rat kidney gamma-glutamyl transferase. Biochimica et Biophysica Acta 884, 207210.CrossRefGoogle Scholar
DeLeve, LD & Kaplowitz, N (1990) Importance and regulation of hepatic glutathione. Seminars in Liver Disease 10, 251266.CrossRefGoogle ScholarPubMed
Deneke, SM, Baxter, DF, Phelps, DT & Fanburg, BL (1989) Increase in endothelial cell glutathione and precursor amino acid uptake by ethyl maleate and hypoxia. American Journal of Physiology 275, L265L271.Google Scholar
Denno, R, Rounds, JD, Faris, R, Holejko, LB & Wilmore, DW (1996) Glutamine-enriched total parenteral nutrition enhances plasma glutathione in resting state. Journal of Surgical Research 61, 3538.CrossRefGoogle ScholarPubMed
Dolphin, D, Poulson, R & Avramovic, O (editors) (1989) Glutathione: Chemical, Biochemical and Medical Aspects. New York: Wiley.Google Scholar
Fläring, U, Wernerman, J & Hammarqvist, F (1999) Muscle glutathione concentrations in critically ill patients. Clinical Nutrition (In the Press).Google Scholar
Hammarqvist, F, Luo, J-L, Andersson, K, Cotgreave, IA & Wernerman, J (1997) Skeletal muscle glutathione is depleted in critically ill patients. Critical Care Medicine 25, 7884.CrossRefGoogle ScholarPubMed
Harward, TRS, Coe, D, Souba, WW, Klingman, N & Seeger, JM (1994) Glutamine preserves gut glutathione levels during intestinal ischemia/reperfusion. Journal of Surgical Research 56, 351355.CrossRefGoogle ScholarPubMed
Hong, RW, Rounds, JD, Helton, WS, Robinson, MK & Wilmore, DW (1992) Glutamine preserves liver glutathione and improves survival after lethal hepatic injury. Annals of Surgery 215, 114119.CrossRefGoogle ScholarPubMed
Jepson, MM, Bates, PC, Broadbent, P, Pell, JM & Millward, DJ (1988) Relationship between glutamine concentration and protein synthesis in rat skeletal muscle. American Journal of Physiology 255, E166E172.Google ScholarPubMed
Larsson, A (1989) Hereditary disorders related to glutathione deficiency. In Glutathione: Chemical, Biochemical, and Medical Aspects, pp. 197234 [Dolphin, D, Avramovic, O and Poulson, R, editors]. New York: Wiley.Google Scholar
Lauterburg, BH, Adams, JD & Mitchell, JR (1984) Hepatic glutathione homeostasis in the rat: efflux accounts for glutathione turnover. Hepatology 4, 586590.CrossRefGoogle ScholarPubMed
Luo, J-L, Hammarqvist, F, Andersson, K & Wernerman, J (1996) Skeletal muscle glutathione following surgical trauma. Annals of Surgery 223, 420427.CrossRefGoogle Scholar
Luo, J-L, Hammarqvist, F, Andersson, K & Wernerman, J (1998) Surgical trauma decreases the synthesis of glutathione in skeletal muscle. American Journal of Physiology 275, E359E365.Google Scholar
Luo, J-L, Hammarqvist, F, Cotgreave, IA, Lind, K, Andersson, K & Wernerman, J (1995) Determination of intracellular glutathione in human skeletal muscle by reversed-phase high-performance liquid chromatography. Journal of Chromatography 670B, 2936.CrossRefGoogle Scholar
Luo, J-L, Hammarqvist, F, Lindholmer, C, Andersson, K & Wernerman, J (1999) Determination of the redox status of glutathione and cysteine in small biopsy specimens of human tissue. Clinical Chemistry (In the Press).Google Scholar
MacLennan, PA, Smith, K, Weryk, B, Watt, PW & Rennie, MJ (1988) Inhibition of protein breakdown by glutamine in perfused rat skeletal muscle. FEBS Letters 237, 133136.CrossRefGoogle ScholarPubMed
Meister, A & Andersson, ME (1983) Glutathione. Annual Review of Biochemistry 52, 711760.CrossRefGoogle ScholarPubMed
Miller, A & Horiuchi, M (1963) Erythrocyte GSH. In vitro incorporation of radioactive amino acid precursors into the GSH of human erythrocytes. Journal of Laboratory and Clinical Medicine 60, 764765.Google Scholar
Novogrodsky, A, Nehring, RE & Meister, A (1979) Inhibition of amino acid transport into lymphoid cells by the glutamine analog L-2-amino-4oxo-5-chloropentanoate. Proceedings of the National Academy of Sciences, USA 76, 49324935.CrossRefGoogle Scholar
Robinson, MK, Rounds, JD, Hong, RW, Jacobs, DO & Wilmore, DW (1992) Glutathione deficiency increases organ dysfunction after hemorrhagic shock. Surgery 112, 140149.Google ScholarPubMed
Srivastava, SK & Beutler, E (1969) The transport of oxidised glutathione from human erythrocytes. Journal of Biological Chemistry 244, 916.CrossRefGoogle ScholarPubMed
Taniguchi, N, Higashi, T, Sakamoto, Y & Meister, A (1989) Glutathione Centennial: Molecular Properties and Clinical Implications. New York: Academic Press.Google Scholar
Welbourne, TC (1979) Ammonia production and glutamine incorporation into glutathione in the functioning rat kidney. Canadian Journal of Biochemistry 57, 233237.CrossRefGoogle ScholarPubMed
Wernerman, J, Hammarqvist, F & Vinnars, E (1990) Alpha-ketoglutarate and postoperative muscle catabolism. Lancet 335, 701703.CrossRefGoogle ScholarPubMed
Westman, B, Hammarqvist, F, Johansson, G, Luo, J-L, Söderlund, K & Wernerman, J (1998) Effects of ischemia and reperfusion on glutathione, energy and amino acid content in muscle following elective surgery of abdominal aneurysm. Hygea 197, 220 Abstr.Google Scholar