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The biochemical basis of antioxidant therapy in critical illness

Published online by Cambridge University Press:  07 March 2007

Simon Eaton
Simon Eaton*
Affiliation:
Unit of Paediatric Surgery and Biochemistry, Endocrinology and Metabolism Unit, Institute of Child Health (University College London), 30 Guilford Street, London WC1N 1EH, UK
*
Corresponding author: Simon Eaton, fax +44 20 7404 6181, email s.eaton@ich.ucl.ac.uk
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Abstract

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During critical illness free radical production may increase as a result of, for example, sepsis or tissue trauma. In addition, because of a potential for increased losses, and the possibility of inadequate nutrition, the antioxidant defences of the body may become compromised. Thus, the delicate balance between free radicals and antioxidants may be disturbed. Various nutritional and pharmacological strategies to enhance antioxidant defences have been proposed, which aim either to maintain or enhance endogenous antioxidant stores or to provide alternative antioxidant agents. Trace elements and amino acids are particularly important, and their synergistic role in the maintenance of the body's antioxidant defence network will be discussed.

Keywords

Critical illnessFree radical productionAntioxidant therapySepsis
Type
BAPEN Symposium 4 on ‘Glutamine and antioxidants in critical care’
Information
Proceedings of the Nutrition Society , Volume 65 , Issue 3 , August 2006 , pp. 242 - 249
Copyright
Copyright © The Nutrition Society 2006

References

Angstwurm, MWA, Schottdorf, J, Schopohl, J & Gaertner, R (1999) Selenium replacement in patients with severe systemic inflammatory response syndrome improves clinical outcome. Critical Care Medicine 27 1807–1813.CrossRefGoogle ScholarPubMed
Avenell, A (2006) Glutamine in critical care: current evidence from systematic reviews. Proceedings of the Nutrition Society 65 000–000.CrossRefGoogle ScholarPubMed
Avenell, A, Noble, DW, Barr, J & Engelhardt, T (2004) Selenium Supplementation for Critically Ill Adults. The Cochrane Database of Systematic Reviews. Bognor Regis, West Sussex: John Wiley & Sons Ltd.Google Scholar
Bar-Or, D, Bar-Or, R, Rael, LT, Gardner, DK, Slone, DS & Craun, ML (2005) Heterogeneity and oxidation status of commercial human albumin preparations in clinical use. Critical Care Medicine 33 1638–1641.CrossRefGoogle ScholarPubMed
Basu, R, Muller, DPR, Papp, E, Merryweather, I, Eaton, S, Klein, N & Pierro, A (1999) Free radical formation in infants: the effect of critical illness, parenteral nutrition, and enteral feeding. Journal of Pediatric Surgery 34 1091–1095.CrossRefGoogle ScholarPubMed
Berger, MM, Baines, M, Chiolero, RL, Wardle, CA, Cayeux, C & Shenkin, A (2001) Influence of early trace element and vitamin E supplements on antioxidant status after major trauma: a controlled trial. Nutrition Research 21 41–54.CrossRefGoogle Scholar
Bernard, GR, Wheeler, AP, Arons, MM, Morris, PE, Paz, HL & Russell, JA, et al. (1997) A trial of antioxidants N-acetylcysteine and procysteine in ARDS. Chest 112 164–172.CrossRefGoogle ScholarPubMed
Beyer, RE (1994) The role of ascorbate in antioxidant protection of biomembranes–interaction with vitamin-E and coenzyme-Q. Journal of Bioenergetics and Biomembranes 26 349–358.CrossRefGoogle ScholarPubMed
Blankenberg, S, Rupprecht, HJ, Bickel, C, Torzewski, M, Hafner, G, Tiret, L, Smieja, M, Cambien, F, Meyer, J & Lackner, KJ (2003) Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease. New England Journal of Medicine 349 1605–1613.CrossRefGoogle ScholarPubMed
Bolanos, JP, Heales, SJR, Peuchen, S, Barker, JE, Land, JM & Clark, JB (1996) Nitric oxide-mediated mitochondrial damage: A potential neuroprotective role for glutathione. Free Radical Biology and Medicine 21 995–1001.CrossRefGoogle Scholar
Borrelli, E, Roux-Lombard, P, Grau, GE, Girardin, E, Ricou, B, Dayer, JM & Suter, PM (1996) Plasma concentrations of cytokines, their soluble receptors, and antioxidant vitamins can predict the development of multiple organ failure in patients at risk. Critical Care Medicine 24 392–397.CrossRefGoogle ScholarPubMed
Brealey, D, Brand, M, Hargreaves, I, Heales, S, Land, J, Smolenski, R, Davies, NA, Cooper, CE & Singer, M (2002) Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet 360 219–223.CrossRefGoogle ScholarPubMed
Christen, S, Woodall, AA, Shigenaga, MK, Southwell-Keely, PT, Duncan, MW & Ames, BN (1997) Gamma-tocopherol traps mutagenic electrophiles such as NO (X) and complements alpha-tocopherol: Physiological implications. Proceedings of the National Academy of Sciences USA 94 3217–3222.CrossRefGoogle ScholarPubMed
Clementi, E, Brown, GC, Feelisch, M & Moncada, S (1998) Persistent inhibition of cell respiration by nitric oxide: Crucial role of S -nitrosylation of mitochondrial complex I and protective action of glutathione. Proceedings of the National Academy of Sciences USA 95 7631–7636.CrossRefGoogle ScholarPubMed
Crimi, E, Liguori, A, Condorelli, M, Cioffi, M, Astuto, M & Bontempo, P, et al. (2004) The beneficial effects of antioxidant supplementation in enteral feeding in critically ill patients: A prospective, randomized, double-blind, placebo-controlled trial. Anesthesia and Analgesia 99 857–863.CrossRefGoogle ScholarPubMed
Critical Care Nutrition (2006) REducing Deaths due to Oxidative Stress Study. http://www.criticalcarenutrition.com/redoxs/redoxHome.htmGoogle Scholar
Cuzzocrea, S, Mazzon, E, Dugo, L, Caputi, AP, Aston, K, Riley, DP & Salvemini, D (2001) Protective effects of a new stable, highly active SOD mimetic, M40401 in splanchnic artery occlusion and reperfusion. British Journal of Pharmacology 132 19–29.CrossRefGoogle ScholarPubMed
Davis, JM, Rosenfeld, WN, Richter, SE, Parad, MR, Gewolb, IH & Spitzer, AR, et al. (1997) Safety and pharmacokinetics of multiple doses of recombinant human CuZn superoxide dismutase administered intratracheally to premature neonates with respiratory distress syndrome. Pediatrics 100 24–30.CrossRefGoogle ScholarPubMed
Denno, R, Rounds, JD, Faris, R, Holejko, LB & Wilmore, DW (1996) Glutamine-enriched total parenteral nutrition enhances plasma glutathione in the resting state. Journal of Surgical Research 61 35–38.CrossRefGoogle ScholarPubMed
Di Napoli, M & Papa, F (2005) M-40403 Metaphore pharmaceuticals. IDrugs 8 67–76.Google ScholarPubMed
Era, S, Kuwata, K, Imai, H, Nakamura, K, Hayashi, T & Sogami, M (1995) Age-related change in redox state of human serum-albumin. Biochimica et Biophysica Acta 1247 12–16.CrossRefGoogle ScholarPubMed
Filipovska, A, Kelso, GF, Brown, SE, Beer, SM, Smith, RAJ & Murphy, MP (2005) Synthesis and characterization of a triphenylphosphonium-conjugated peroxidase mimetic–Insights into the interaction of ebselen with mitochondria. Journal of Biological Chemistry 280 24113–24126.CrossRefGoogle ScholarPubMed
Flaring, UB, Rooyackers, OE, Wernerman, J & Hammarqvist, F (2003) Glutamine attenuates post-traumatic glutathione depletion in human muscle. Clinical Science (London) 104 275–282.CrossRefGoogle ScholarPubMed
Halliwell, B (1988) Albumin–an important extracellular antioxidant. Biochemical Pharmacology 37 569–571.CrossRefGoogle ScholarPubMed
Han, D, Handelman, G, Marcocci, L, Sen, CK, Roy, S, Kobuchi, H, Tritschler, HJ, Flohe, L & Packer, L (1997) Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. Biofactors 6 321–338.CrossRefGoogle ScholarPubMed
Hardy, G (2005) Selenium: an important component of sepsis therapy. British Journal of Intensive Care 15 28–36.Google Scholar
Hayakawa, A, Kuwata, K, Era, S, Sogami, M, Shimonaka, H, Yamamoto, M, Dohi, S & Hirose, H (1997) Alteration of redox state of human serum albumin in patients under anesthesia and invasive surgery. Journal of Chromatography 698B 27–33.CrossRefGoogle Scholar
Health Services Research Unit, University of Aberdeen (2006) Scottish multicentre trial of glutamine and selenium supplemented parenteral nutrition for critically ill patients (SIGNET trial). http://www.abdn.ac.uk/hsru/hta/signet.shtmlGoogle Scholar
Heyland, DK, Dhaliwal, R, Suchner, U & Berger, MM (2005) Antioxidant nutrients: a systematic review of trace elements and vitamins in the critically ill patient. Intensive Care Medicine 31 327–337.CrossRefGoogle ScholarPubMed
Hong, RW, Rounds, JD, Helton, WS, Robinson, MK & Wilmore, DW (1992) Glutamine preserves liver glutathione after lethal hepatic–injury. Annals of Surgery 215 114–119.CrossRefGoogle ScholarPubMed
Jackson, MJ, Broome, CS & McArdle, F (2003) Marginal dietary selenium intakes in the UK: Are there functional consequences. Journal of Nutrition 133 1557S–1559S.CrossRefGoogle ScholarPubMed
Jaeschke, H (1992) Enhanced sinusoidal glutathione efflux during endotoxin-induced oxidant stress in vivo. American Journal of Physiology 263 G60–G68.Google ScholarPubMed
Johnston, CS & Cox, SK (2001) Plasma-saturating intakes of vitamin C confer maximal antioxidant protection to plasma. Journal of the American College of Nutrition 20 623–627.CrossRefGoogle ScholarPubMed
Lacey, JM & Wilmore, DW (1990) Is glutamine a conditionally essential amino acid. Nutrition Reviews 48 297–309.CrossRefGoogle ScholarPubMed
Laurent, A, Alary, J, Debrauwer, L & Cravedi, JP (1999) Analysis in the rat of 4-hydroxynonenal metabolites excreted in bile: Evidence of enterohepatic circulation of these byproducts of lipid peroxidation. Chemical Research in Toxicology 12 887–894.CrossRefGoogle ScholarPubMed
Lauterburg, BH, Adams, JD & Mitchell, JR (1984) Hepatic glutathione homeostasis in the rat–efflux accounts for glutathione turnover. Hepatology 4 586–590.CrossRefGoogle ScholarPubMed
Luo, JL, Hammarqvist, F, Andersson, K & Wernerman, J (1996) Skeletal muscle glutathione after surgical trauma. Annals of Surgery 223 420–427.CrossRefGoogle ScholarPubMed
Lyons, J, Rauh-Pfeiffer, A, Ming-Yu, Y, Lu, XM, Zurakowski, D & Curley, M, et al. (2001) Cysteine metabolism and whole blood glutathione synthesis in septic pediatric patients. Critical Care Medicine 29 870–877.CrossRefGoogle ScholarPubMed
Malmezat, T, Breuille, D, Capitan, P, Mirand, PP & Obled, C (2000a) Glutathione turnover is increased during the acute phase of sepsis in rats. Journal of Nutrition 130 1239–1246.CrossRefGoogle ScholarPubMed
Malmezat, T, Breuille, D, Pouyet, C, Buffiere, C, Denis, P, Mirand, PP & Obled, C (2000b) Methionine transsulfuration is increased during sepsis in rats. American Journal of Physiology 279 E1391–E1397.Google ScholarPubMed
Malmezat, T, Breuille, D, Pouyet, C, Mirand, PP & Obled, C (1998) Metabolism of cysteine is modified during the acute phase of sepsis in rats. Journal of Nutrition 128 97–105.CrossRefGoogle ScholarPubMed
Markley, MA, Pierro, A & Eaton, S (2002) Hepatocyte mitochondrial metabolism is inhibited in neonatal rat endotoxaemia: effects of glutamine. Clinical Science (London) 102 337–344.CrossRefGoogle ScholarPubMed
Melov, S, Ravenscroft, J, Malik, S, Gill, MS, Walker, DW, Clayton, PE, Wallace, DC, Malfroy, B, Doctrow, SR & Lithgow, GJ (2000) Extension of life span with superoxide dismutase/catalase mimetics. Science 289 1567.CrossRefGoogle ScholarPubMed
Meyer, A, Buhl, R, Kampf, S & Magnussen, H (1995) Intravenous N-acetylcysteine and lung glutathione of patients with pulmonary fibrosis and normals. American Journal of Respiratory and Critical Care Medicine 152 1055–1060.CrossRefGoogle ScholarPubMed
Miller, NJ, Rice-Evans, C, Davies, MJ, Gopinathan, V & Milner, A (1993) A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clinical Science (London) 84 407–412.CrossRefGoogle ScholarPubMed
Minamiyama, Y, Takemura, S, Koyama, K, Yu, H, Miyamoto, M & Inoue, M (1996) Dynamic aspects of glutathione and nitric oxide metabolism in endotoxemic rats. American Journal of Physiology 271 G575–G581.Google ScholarPubMed
Moberly, JB, Logan, J, Borum, PR, Story, KO, Webb, LE & Jassal, SV, et al. (1998) Elevation of whole-blood glutathione in peritoneal dialysis patients by L-2-oxothiazolidine-4-carboxylate, a cysteine prodrug (Procysteine®). Journal of the American Society of Nephrology 9 1093–1099.CrossRefGoogle ScholarPubMed
Morton, LW, Ward, NC, Croft, KD & Puddey, IB (2002) Evidence for the nitration of gamma-tocopherol in vivo: 5-nitro-gamma-tocopherol is elevated in the plasma of subjects with coronary heart disease. Biochemical Journal 364 625–628.CrossRefGoogle ScholarPubMed
Nathens, AB, Neff, MJ, Jurkovich, GJ, Klotz, P, Farver, K, Ruzinski, JT, Radella, F, Garcia, I & Maier, RV (2002) Randomized, prospective trial of antioxidant supplementation in critically ill surgical patients. Annals of Surgery 236 814–822.CrossRefGoogle ScholarPubMed
Ogawa, A, Yoshimoto, T, Kikuchi, H, Sano, K, Saito, I, Yamaguchi, T & Yasuhara, H (1999) Ebselen in acute middle cerebral artery occlusion: A placebo-controlled, double-blind clinical trial. Cerebrovascular Diseases 9 112–118.CrossRefGoogle ScholarPubMed
Ookhtens, M, Mittur, AV & Erhart, NA (1994) Changes in plasma glutathione concentrations, turnover, and disposal in developing rats. American Journal of Physiology 266 R979–R988.Google ScholarPubMed
Ortolani, O, Conti, A, De Gaudio, AR, Moraldi, E, Cantini, Q & Novelli, G (2000) The effect of glutathione and N-acetylcysteine on lipoperoxidative damage in patients with early septic shock. American Journal of Respiratory and Critical Care Medicine 161 1907–1911.CrossRefGoogle ScholarPubMed
Poon, BY, Goddard, CM, Leaf, CD, Russell, JA & Walley, KR (1998) L-2-oxothiazolidine-4-carboxylic acid prevents endotoxin-induced cardiac dysfunction. American Journal of Respiratory and Critical Care Medicine 158 1109–1113.CrossRefGoogle ScholarPubMed
Pope, SAS, Green, H, Clayton, PT, Goss-Sampson, MA & Muller, DPR (2002) The possible use of urinary alpha-tocopheronolactone as a biomarker of oxidative stress. Free Radical Research 36 82–83.Google Scholar
Porras, P, Pedrajas, JR, Martinez-Galisteo, E, Padilla, CA, Johansson, C, Holmgren, A & Barcena, JA (2002) Glutaredoxins catalyze the reduction of glutathione by dihydrolipoamide with high efficiency. Biochemical and Biophysical Research Communications 295 1046–1051.CrossRefGoogle ScholarPubMed
Pullar, JM, Vissers, MCM & Winterbourn, CC (2001) Glutathione oxidation by hypochlorous acid in endothelial cells produces glutathione sulfonamide as a major product but not glutathione disulfide. Journal of Biological Chemistry 276 22120–22125.CrossRefGoogle Scholar
Quasim, T, McMillan, DC, Talwar, D, Sattar, N, O'Reilly, DSJ & Kinsella, J (2003) Lower concentrations of carotenoids in the critically-ill patient are related to a systemic inflammatory response and increased lipid peroxidation. Clinical Nutrition 22 459–462.CrossRefGoogle ScholarPubMed
Quinlan, GJ, Margarson, MP, Mumby, S, Evans, TW & Gutteridge, JMC (1998) Administration of albumin to patients with sepsis syndrome: a possible beneficial role in plasma thiol repletion. Clinical Science (London) 95 459–465.CrossRefGoogle ScholarPubMed
Quinlan, GJ, Mumby, S, Martin, GS, Bernard, GR, Gutteridge, JMC & Evans, TW (2004) Albumin influences total plasma antioxidant capacity favorably in patients with acute lung injury. Critical Care Medicine 32 755–759.CrossRefGoogle ScholarPubMed
Rayman, MP (2000) The importance of selenium to human health. Lancet 356 233–241.CrossRefGoogle ScholarPubMed
Riedl, CR, Sternig, P, Galle, G, Langmann, F, Vcelar, B, Vorauer, K, Wagner, A, Katinger, H & Pfluger, H (2005) Liposomal recombinant human superoxide dismutase for the treatment of Peyronie's disease: A randomized placebo-controlled double-blind prospective clinical study. European Urology 48 656–661.CrossRefGoogle ScholarPubMed
Roes, EM, Raijmakers, MTM, Peters, WHM & Steegers, EAP (2002) Effects of oral N -acetylcysteine on plasma homocysteine and whole blood glutathione levels in healthy, non-pregnant women. Clinical Chemistry and Laboratory Medicine 40 496–498.CrossRefGoogle Scholar
Saito, I, Asano, T, Sano, K, Takakura, K, Abe, H, Yoshimoto, T, Kikuchi, H, Ohta, T & Ishibashi, S (1998) Neuroprotective effect of an antioxidant, ebselen, in patients with delayed neurological deficits after aneurysmal subarachnoid hemorrhage. Neurosurgery 42 269–277.CrossRefGoogle ScholarPubMed
Salvemini, D & Cuzzocrea, S (2003) Therapeutic potential of superoxide dismutase mimetics as therapeutic agents in critical care medicine. Critical Care Medicine 31 S29–S38.CrossRefGoogle ScholarPubMed
Schuller-Levis, GB & Park, E (2004) Taurine and its chloramine: modulators of immunity. Neurochemical Research 29 117–126.CrossRefGoogle ScholarPubMed
Simon, EJ, Eisengart, A, Sundheim, L & Milhorat, AT (1956) Metabolism of vitamin-E. 2. purification and characterization of urinary metabolites of alpha-tocopherol. Journal of Biological Chemistry 221 807–817.CrossRefGoogle Scholar
Soejima, A, Matsuzawa, N, Hayashi, T, Kimura, R, Ootsuka, T, Fukuoka, K, Yamada, A, Nagasawa, T & Era, S (2004) Alteration of redox state of human serum albumin before and after hemodialysis. Blood Purification 22 525–529.CrossRefGoogle ScholarPubMed
Stocker, R, Yamamoto, Y, McDonagh, AF, Glazer, AN & Ames, BN (1987) Bilirubin is an antioxidant of possible physiological importance. Science 235 1043–1046.CrossRefGoogle ScholarPubMed
Sugino, K, Dohi, K, Yamada, K & Kawasaki, T (1989) Changes in the levels of endogenous antioxidants in the liver of mice with experimental endotoxemia and the protective effects of the antioxidants. Surgery 105 200–206.Google ScholarPubMed
Suzuki, E, Yasuda, K, Takeda, N, Sakata, S, Era, S, Kuwata, K, Sogami, M & Miura, K (1992) Increased oxidized form of human serum albumin in patients with diabetes mellitus. Diabetes Research and Clinical Practice 18 153–158.CrossRefGoogle ScholarPubMed
Terawaki, H, Yoshimura, K, Hasegawa, T, Matsuyama, Y, Negawa, T, Yamada, K, Matsushima, M, Nakayama, M, Hosoya, T & Era, S (2004) Oxidative stress is enhanced in correlation with renal dysfunction: examination with the redox state of albumin. Kidney International 66 1988–1993.CrossRefGoogle ScholarPubMed
Tuder, RM, Zhen, L, Cho, CY, Taraseviciene-Stewart, L, Kasahara, Y, Salvemini, D, Voelkel, NF & Flores, SC (2003) Oxidative stress and apoptosis interact and cause emphysema due to vascular endothelial growth factor receptor blockade. American Journal of Respiratory Cell and Molecular Biology 29 88–97.CrossRefGoogle ScholarPubMed
Valencia, E, Marin, A & Hardy, G (2002) Impact of oral L-glutamine on glutathione, glutamine, and glutamate blood levels in volunteers. Nutrition 18 367–370.CrossRefGoogle ScholarPubMed
Wang, W & Ballatori, N (1998) Endogenous glutathione conjugates: Occurrence and biological functions. Pharmacological Reviews 50 335–355.Google ScholarPubMed
Waring, WS, Webb, DJ & Maxwell, SR (2001) Systemic uric acid administration increases serum antioxidant capacity in healthy volunteers. Journal of Cardiovascular Pharmacology 38 365–371.CrossRefGoogle ScholarPubMed
Wessner, B, Strasser, EM, Spittler, A & Roth, E (2003) Effect of single and combined supply of glutamine, glycine, N-acetylcysteine, and R, S -alpha-lipoic acid on glutathione content of myelomonocytic cells. Clinical Nutrition 22 515–522.CrossRefGoogle Scholar
Yamaguchi, T, Sano, K, Takakura, K, Saito, I, Shinohara, Y, Asano, T & Yasuhara, H (1998) Ebselen in acute ischemic stroke–A placebo-controlled, double-blind clinical trial. Stroke 29 12–17.CrossRefGoogle ScholarPubMed
Yang, SL, Koo, DJ, Chaudry, IH & Wang, P (2001) Glycine attenuates hepatocellular depression during early sepsis and reduces sepsis-induced mortality. Critical Care Medicine 29 1201–1206.CrossRefGoogle ScholarPubMed