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Electrophilic methyl groups present in the diet ameliorate pathological states induced by reductive and oxidative stress: a hypothesis

Published online by Cambridge University Press:  09 March 2007

Miklós Ghyczy*
Affiliation:
Rhône-Poulenc Rorer Co., Cologne, Germany
Mihály Boros
Affiliation:
Institute of Surgical Research, University of Szeged, Hungary
*
*Corresponding author: Dr Miklós Ghyezy, fax +49 221 509 2816, email miklos.ghyczy@aventis.com
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Abstract

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Reductive stress, characterised by an increased NADH:NAD+ ratio, may be as common and as important a consequence of redox imbalance as oxidative stress. It may also be an important predisposing cause of the generation of reactive oxygen species. Considerable experimental and indirect clinical evidence suggests that protection against reductive stress depends on biomolecules with electrophilic methyl groups (EMG) such as S-adenosylmethionine, betaine, carnitine and phosphatidylcholine. Pathological processes leading to reductive stress and their relief by such protective agents is reviewed and the proposed molecular mechanism is outlined. These and other EMG-containing biomolecules are part of the daily diet and may represent an important control system for redox balance.

Type
Review article
Copyright
Copyright © The Nutrition Society 2001

References

Aleynik, SI, Leo, MA, Ma, X, Aleynik, MK & Lieber, CS (1997) Polyenylphosphatidylcholine prevents carbon tetrachloride-induced lipid peroxidation while it attenuates liver fibrosis. Journal of Hepatology 27, 554561.CrossRefGoogle ScholarPubMed
Arias-Diaz, J, Vara, E, Garcia, C, Villa, N, Rodriguez, JM, Ortiz, P & Balibrea, JL (1996) S-adenosylmethionine protects hepatocytes against the effects of cytokines. Journal of Surgical Research 62, 7984.CrossRefGoogle ScholarPubMed
Balazsovits, JA, Mayer, LD, Bally, MB, Cullis, PR, McDonell, M, Ginsberg, RS & Falk, RE (1989) Analysis of the effect of liposome encapsulation on the vesicant properties, acute and cardiac toxicities, and antitumor efficacy of doxorubicin. Cancer Chemotherapy and Pharmacology 23, 8186.CrossRefGoogle ScholarPubMed
Barak, AJ, Beckenhauer, HC, Badakhsh, S & Tuma, DJ (1997) The effect of betaine in reversing alcoholic steatosis. Alcohol Clinical and Experimental Research 21, 11001102.CrossRefGoogle ScholarPubMed
Barak, A, Beckenhauer, HC, Junnila, M & Tuma, DJ (1993) Dietary betaine promotes generation of hepatic S-adenosylmethionine and protects the liver from ethanol-induced fatty infiltration. Alcohol Clinical and Experimental Research 17, 552555.CrossRefGoogle ScholarPubMed
Barak, AJ, Beckenhauer, HC & Tuma, DJ (1994) S-adenosylmethionine generation and prevention of alcoholic fatty liver by betaine. Alcohol 11, 501503.CrossRefGoogle ScholarPubMed
Bertelli, A, Cerrati, A, Giovannini, L, Mian, M, Spaggiari, P & Bertelli, AA (1993) Protective action of L-carnitine and coenzyme Q10 against hepatic triglyceride infiltration induced by hyperbaric oxygen and ethanol. Drugs Experimental and Clinical Research 19, 6568.Google ScholarPubMed
Blusztajn, JK (1998) Choline, a vital amine. Science 281, 794795.CrossRefGoogle ScholarPubMed
Broderick, TL, Quinney, HA, Barker, CC & Lopaschuk, GD (1993) Beneficial effect of carnitine on mechanical recovery of rat hearts reperfused after a transient period of global ischemia is accompanied by a stimulation of glucose oxidation. Circulation 87, 972981.CrossRefGoogle ScholarPubMed
Broderick, TL, Quinney, HA & Lopaschuk, GD (1995) L-carnitine increases glucose metabolism and mechanical function following ischaemia in diabetic rat heart. Cardiovascular Research 29, 373378.CrossRefGoogle ScholarPubMed
Cha, YS & Sachan, DS (1995) Acetylcarnitine-mediated inhibition of ethanol oxidation in hepatocytes. Alcohol 12, 289294.CrossRefGoogle ScholarPubMed
Corbucci, GG, Menichetti, A, Cogliatti, A, Nicoli, P & Ruvolo, C (1992) Metabolic aspects of acute tissue hypoxia during extracorporeal circulation and their modification induced by L-carnitine treatment. International Journal of Clinical Pharmacology Research 12, 149157.Google ScholarPubMed
Diplock, AT, Aggett, PJ, Aswell, M, Bornet, F, Fern, EB & Roberfroid, MB (1999) Scientific concepts of functional foods in Europe: consensus document. British Journal of Nutrition 81, S1S27.Google Scholar
Diplock, AT, Charleux, J-L, Crozier-Willi, G, Kok, FJ, Rice-Evans, C, Roberfroid, M, Stahl, W & Vina-Ribes, J (1998) Functional food science and defence against reactive oxidative. British Journal of Nutrition 80, S77S112.CrossRefGoogle ScholarPubMed
Duan, J & Karmazyn, M (1990) Protection of the reperfused ischemic isolated rat heart by phosphatidylcholine. Journal of Cardiovascular Pharmacology 15, 163171.CrossRefGoogle ScholarPubMed
Duan, J & Moffat, MP (1990) Protective effects of phosphatidylcholine against mechanisms of ischemia and reperfusion-induced arrhythmias in isolated guinea pig ventricular tissues. Naunyn-Schmiedeberg′s Archives of Pharmacology 342, 342348.CrossRefGoogle ScholarPubMed
Duce, AM, Ortíz, P, Cabrero, C & Mato, JM (1988) S-adenosyl-L-methionine synthetase and phospholipid methyltransferase are inhibited in human cirrhosis. Hepatology 8, 6568.CrossRefGoogle ScholarPubMed
Dunjic, BS, Axelson, J, Ar′Rajab, A, Larsson, K & Bengkmark, S (1993) Gastroprotective capability of exogenous phosphatidylcholine in experimentally induced chronic gastric ulcers in rats. Scandinavian Journal of Gastroenterology 28, 8994.CrossRefGoogle ScholarPubMed
Dunne, JB, Davenport, M, Williams, R & Tredger, JM (1994) Evidence that S-adenosylmethionine and N-acetylcysteine reduce injury from sequential cold and warm ischemia in the isolated perfused rat liver. Transplantation 57, 11611168.CrossRefGoogle ScholarPubMed
Dunne, JB, Piratvisuth, T, Williams, R & Tredger, JM (1997) Treatment of experimental ischemia/reperfusion injury with S-adenosylmethionine: Evidence that donor pretreatment complements other regimens. Transplantation 63, 500506.CrossRefGoogle ScholarPubMed
Feo, F, Pascale, R, Garcea, R, Daino, L, Pirisi, L, Frassetto, S, Ruggiu, ME, Di Padova, C & Stramentinoli, G (1986) Effect of the variations of S-adenosyl-L-methionine liver content on fat accumulation and ethanol metabolism in ethanol-intoxicated rats. Toxicology and Applied Pharmacology 83, 331341.CrossRefGoogle ScholarPubMed
Fernandez, E, Galan, AI, Moran, D, Gonzalez-Buitrago, JM, Munoz, ME & Jimenez, R (1995) Reversal of cyclosporine A-induced alterations in biliary secretion by S-adenosyl-L-methionine in rats. Journal of Pharmacology and Experimental Therapeutics 275, 442449.Google ScholarPubMed
Gabizon, A, Meshorer, A & Barenholz, Y (1986) Comparative long-term study of the toxicities of free and liposome-associated doxorubicin in mice after intravenous administration. Journal of the National Cancer Institute 77, 459469.Google ScholarPubMed
Garcia-Ruiz, C, Morales, A, Colell, A, Ballelsta, A, Rodes, J, Kaplowitz, N & Fernandez-Checa, JC (1995) Feeding S-adenosyl-L-methionine attenuates both ethanol-induced depletion of mitochondrial glutathione and mitochondrial dysfunction in periportal and perivenous rat hepatocytes. Hepatology 21, 207214.CrossRefGoogle ScholarPubMed
Garro, AJ, McBeth, DL, Lima, V & Lieber, CS (1991) Ethanol consumption inhibits fetal DNA methylation in mice: implications for the fetal alcohol syndrome. Alcohol Clinical and Experimental Research 15, 395398.CrossRefGoogle ScholarPubMed
Gilbert, BE, Knight, C, Alvarez, FG, Waldrep, C, Rodarte, JR, Knight, V & Eschenbacher, WL (1997) Tolerance of volunteers to cyclosporine A-dilauroylphosphatidylcholine liposome aerosol. American Journal of Respiration Critical Care Medicine 156, 17891793.CrossRefGoogle ScholarPubMed
Giovannini, L, Palla, R, Bertelli, AA, Migliori, M, Panichi, V, Andreini, B, De Pietro, S & Bertelli, A (1996) Cyclosporine nephrotoxicity evaluated by tissue calcium deposition and tubular enzymes is prevented by L-propionylcarnitine in isolated perfused rat kidney. Transplantation Proceedings 28, 31223125.Google ScholarPubMed
Hensley, K, Kotake, Y, Sang, H, Pye, QN, Wallis, GL, Kolker, LM, Tabatabaie, T, Stewart, CE, Konishi, Y, Nakae, D & Floyd, RE (2000) Dietary choline restriction causes complex I dysfunction and increased H2O2 generation in liver mitochondria. Carcinogenesis 21, 983989.CrossRefGoogle Scholar
Jaeschke, H, Kleinwaechter, C & Wendel, A (1992) NADH-dependent reductive stress and ferritin-bound iron in allyl alcohol-induced lipid peroxidation in vivo: the protective effect of vitamin E. Chemical Biology Interactions 81, 5768.CrossRefGoogle ScholarPubMed
Khan, S & O′Brien, PJ (1995) Modulating hypoxia-induced hepatocyte injury by affecting intracellular redox state. Biochimica et Biophysica Acta 1269, 153161.CrossRefGoogle ScholarPubMed
Laudanno, OM, Finkelstein, D & Capdepon, E (1987) Complete cytoprotective action on the gastroduodenal mucosa induced by SAM against damage provoked by ethanol in man. Panminerva Medica 29, 7578.Google Scholar
Leyck, S, Dereu, N, Etschenberg, E, Ghyczy, M, Graf, E, Winkelmann, J & Parnham, MJ (1985) Improvement of the gastric tolerance of non-steroidal antiinflammatory drugs by polyene phosphatidylcholine (Phospholipon 100). European Journal of Pharmacology 117, 3542.CrossRefGoogle Scholar
Lichtenberger, LM, Graziani, LA, Dial, EJ, Butler, BD & Hills, BA (1982) Role of surface-active phospholipids in gastric cytoprotection. Science 219, 13271329.CrossRefGoogle Scholar
Lieber, CS (1997) Role of oxidative stress and antioxidant therapy in alcoholic and nonalcoholic liver diseases. Advances in Pharmacology 38, 601628.CrossRefGoogle ScholarPubMed
Lieber, CS, Casini, A, De Carli, LM, Kim, CI, Lowe, N, Sasaki, R & Leo, MA (1990 a) S-adenosyl-L-methionine attenuates alcohol-induced liver injury in the baboon. Hepatology 11, 165172.CrossRefGoogle ScholarPubMed
Lieber, CS, De Carli, LM, Mak, KM, Kim, CI & Leo, MA (1990 b) Attenuation of alcohol-induced hepatic fibrosis by polyunsaturated lecithin. Hepatology 12, 13901398.CrossRefGoogle ScholarPubMed
Lieber, CS, Leo, MA, Aleynik, SI, Aleynik, MK & DeCarli, LM (1997) Polyenylphosphatidylcholine decreases alcohol-induced oxidative stress in the baboon. Alcohol Clinical Experimental Research 21, 375379.CrossRefGoogle ScholarPubMed
Lieber, CS, Robins, SJ & Leo, MA (1994 a) Hepatic phosphatidylethanolamine methyltransferase activity is decreased by ethanol and increased by phosphatidylcholine. Alcoholism Clinical and Experimental Research 18, 592595.CrossRefGoogle ScholarPubMed
Lieber, CS, Robins, SJ, Li, J, De Carli, LM, Mak, KM, Fasulo, JM & Leo, MA (1994 a) Phosphatidylcholine protects against fibrosis and cirrhosis in the baboon. Gastroenterology 106, 152159.CrossRefGoogle ScholarPubMed
Niknahad, H, Khan, S & O′Brien, PJ (1995) Hepatocyte injury resulting from the inhibition of mitochondrial respiration at low oxygen concentrations involves reductive stress and oxygen activation. Chemical Biology Interaction 98, 2744.CrossRefGoogle ScholarPubMed
Packer, L, Valenza, M, Serbinova, E, Starke-Reed, P, Frost, K & Kagan, V (1991) Free radical scavenging is involved in the protective effect of L-propionyl-carnitine against ischemia-reperfusion injury of the heart. Archives of Biochemistry and Biophysics 288, 533537.CrossRefGoogle Scholar
Panos, MZ, Polson, R, Johnson, R, Portman, B & Williams, R (1990) Polyunsaturated phosphatidyl choline for acute alcoholic hepatitis: a double-blind, randomized, placebo-contolled trial. Journal of Gastroenterology and Hepatology 2, 351355.Google Scholar
Poirier, LA (1994) Methyl group deficiency in hepatocarcinogenesis. Drug Metabolism Review 26, 185199.CrossRefGoogle ScholarPubMed
Rhew, TH & Sachan, DS (1986) Dose-dependent lipotropic effect of carnitine in chronic alcoholic rats. Journal of Nutrition 116, 22632269.CrossRefGoogle ScholarPubMed
Roman, ID, Johnson, GD & Coleman, R (1996) S-adenosyl-L-methionine prevents disruption of canalicular function and pericanalicular cytoskeleton integrity caused by cyclosporin A in isolated rat hepatocyte couplets. Hepatology 24, 134140.CrossRefGoogle ScholarPubMed
Sachan, DS & Cha, YS (1994) Acetylcarnitine inhibits alcohol dehydrogenase. Biochemical Biophysical Research Communications 203, 14961501.CrossRefGoogle ScholarPubMed
Sachan, DS, Rhew, TH & Ruark, RA (1984) Ameliorating effects of carnitine and its precursors on alcohol-induced fatty liver. American Journal of Clinical Nutrition 39, 738744.CrossRefGoogle ScholarPubMed
Shinozuka, H, Lombardi, B, Sell, S & Iammarino, RM (1978) Early histological and functional alterations of ethionine liver. Cancer Research 38, 10921098.Google ScholarPubMed
Soehngen, EC, Godin-Ostro, E, Fielder, FG, Ginsberg, RS, Slusher, MA & Weiner, AL (1987) Encapsulation of indomethacin in liposomes provides protection against both gastric and intestinal ulceration when orally administered to rats. Arthritis Rheumatology 31, 110.Google Scholar
Stäubli, A & Boelsterli, UA (1998) The labile iron pool in hepatocytes: prooxidant-induced increase in free iron precedes oxidative cell injury. American Journal of Physiology 274, G1031G1037.Google ScholarPubMed
Stoffel, W, Le Kim, D & Tschung, TS (1971) A simple chemical method for labelling phosphatidylcholine and sphingomyelin in the choline moiety. Zeitschrift für Physiologische Chemie 352, 10581064.CrossRefGoogle ScholarPubMed
Storm, G, Van Hoesel, QG, De Groot, G, Kop, W, Steerenberg, PA & Hillen, FC (1989) A comparative study on the antitumor effect, cardiotoxicity and nephrotoxicity of doxorubicin given as a bolus, continuous infusion or entrapped in liposomes in the Lou/M Wsl rat. Cancer Chemotherapy and Pharmacology 24, 341348.CrossRefGoogle ScholarPubMed
Swarm, RA, Ashley, SW, Soybel, DI, Ordway, FS & Cheung, LY (1987) Protective effect of exogenous phospholipid on aspirin-induced gastric mucosal injury. American Journal of Surgery 153, 4853.CrossRefGoogle ScholarPubMed
Szelenyi, I & Engler, H (1986) Cytoprotective role of gastric surfactant in the ethanol-produced gastric mucosal injury of the rat. Pharmacology 33, 199205.CrossRefGoogle ScholarPubMed
Vara, E, Arias-Diaz, J, Garcia, C, Villa, N, Simon, C, Ortiz, P & Balibrea, JL (1994) S-adenosyl-methionine may protect transplanted hepatocytes against the toxic effects of cytokines. Transplantation Proceedings 26, 33643366.Google ScholarPubMed
Winter, BK, Fiskum, G & Gallo, LL (1995) Effects of L-carnitine on serum triglyceride and cytokine levels in rat models of cachexia and septic shock. British Journal of Cancer 72, 11731179.CrossRefGoogle ScholarPubMed
Zeisel, SH, Da Costa, KA, Franklin, PD, Alexander, EA, Lamont, JT, Sheard, NF & Beiser, A (1991) Choline, an essential nutrient for humans. FASEB Journal 5, 20932098.CrossRefGoogle ScholarPubMed
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