Alcohol
Volume 32, Issue 3 , Pages 175-186 , April 2004

Ethanol and acetaldehyde in alcoholic cardiomyopathy: from bad to ugly en route to oxidative stress

  • Xiaochun Zhang

      Affiliations

    • Division of Pharmaceutical Sciences, Graduate Neuroscience Program, and Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071-3375, USA
    • ,
  • Shi-Yan Li

      Affiliations

    • Division of Pharmaceutical Sciences, Graduate Neuroscience Program, and Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071-3375, USA
    • ,
  • Ricardo A Brown

      Affiliations

    • Biomedical Research Branch, Division of Basic Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-7003, USA
    • ,
  • Jun Ren

      Affiliations

    • Division of Pharmaceutical Sciences, Graduate Neuroscience Program, and Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071-3375, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1-307-766-6131; fax: +1-307-766-2953.

Received 24 September 2003 ,Revised 21 January 2004 ,Accepted 23 January 2004.

References 

  1. Aberle NS, Privratsky JR, Burd L, Ren J. Combined acetaldehyde and nicotine exposure depresses cardiac contraction in ventricular myocytes: prevention by folic acid. Neurotoxicol Teratol. 2003;25:731–736
  2. Aberle NS, Ren J. Experimental assessment of the role of acetaldehyde in alcoholic cardiomyopathy. Biol Proced Online. 2003;5:1–12
  3. Aberle NS, Ren J. Short-term acetaldehyde exposure depresses ventricular myocyte contraction: role of cytochrome P450 oxidase, xanthine oxidase, and lipid peroxidation. Alcohol Clin Exp Res. 2003;27:577–583
  4. Albano E, Clot P, Comoglio A, Dianzani MU, Tomasi A. Free radical activation of acetaldehyde and its role in protein alkylation. FEBS Lett. 1994;348:65–69
  5. Badger TM, Ronis MJJ, Seitz HK, Albano E, Ingelman-Sundberg M, Lieber CS. Alcohol metabolism: role in toxicity and carcinogenesis. Alcohol Clin Exp Res. 2003;27:336–347
  6. Bailey SM, Pietsch EC, Cunningham CC. Ethanol stimulates the production of reactive oxygen species at mitochondrial complexes I and III. Free Radic Biol Med. 1999;27:891–900
  7. Baraona E, Abittan CS, Dohmen K, Moretti M, Pozzato G, Chayes ZW, et al. Gender differences in pharmacokinetics of alcohol. Alcohol Clin Exp Res. 2001;25:502–507
  8. Boh EE, Baricos WH, Bernofsky C, Steele RH. Mitochondrial chemiluminescence elicited by acetaldehyde. J Bioenerg Biomembr. 1982;14:115–133
  9. Brien JF, Loomis CW. Pharmacology of acetaldehyde. Can J Physiol Pharmacol. 1983;61:1–22
  10. Brown RA, Anthony MJ, Petrovski P, Ren J. The influence of gender, diabetes, and acetaldehyde on the intrinsic contractile properties of isolated rat myocardium. Cardiovasc Toxicol. 2001;1:35–42
  11. Brown RA, Carpentier RG. Effects of acetaldehyde on the automaticity of the guinea pig sinus node. Alcohol. 1989;6:103–107
  12. Brown RA, Carpentier RG. Effects of acetaldehyde on membrane potentials of sinus node pacemaker fibers. Alcohol. 1990;7:33–36
  13. Brown RA, Jefferson L, Sudan N, Lloyd TC, Ren J. Acetaldehyde depresses myocardial contraction and cardiac myocyte shortening in spontaneously hypertensive rats: role of intracellular Ca2+. Cell Mol Biol (Noisy-le-grand). 1999;45:453–465
  14. Brown RA, Savage AO. Effects of acute acetaldehyde, chronic ethanol, and pargyline treatment on agonist responses of the rat aorta. Toxicol Appl Pharmacol. 1996;136:170–178
  15. Camougrand N, Rigoulet M. Aging and oxidative stress: studies of some genes involved both in aging and in response to oxidative stress. Respir Physiol. 2001;128:393–401
  16. Cao Q, Mak KM, Lieber CS. Dilinoleoylphosphatidylcholine decreases acetaldehyde-induced TNF-α generation in Kupffer cells of ethanol-fed rats. Biochem Biophys Res Commun. 2002;299:459–464
  17. Cederbaum AI, Wu D, Mari M, Bai J. CYP2E1-dependent toxicity and oxidative stress in HepG2 cells. Free Radic Biol Med. 2001;31:1539–1543
  18. Che W, Asahi M, Takahashi M, Kaneto H, Okado A, Higashiyama S, et al. Selective induction of heparin-binding epidermal growth factor-like growth factor by methylglyoxal and 3-deoxyglucosone in rat aortic smooth muscle cells. The involvement of reactive oxygen species formation and a possible implication for atherogenesis in diabetes. J Biol Chem. 1997;272:18453–18459
  19. Chen A, Davis BH. The DNA binding protein BTEB mediates acetaldehyde-induced, Jun N-terminal kinase-dependent αI(I) collagen gene expression in rat hepatic stellate cells. Mol Cell Biol. 2000;20:2818–2826
  20. Chen Y-C, Lu R-B, Peng G-S, Wang M-F, Wang H-K, Ko H-C, et al. Alcohol metabolism and cardiovascular response in an alcoholic patient homozygous for the ALDH2∗2 variant gene allele. Alcohol Clin Exp Res. 1999;23:1853–1860
  21. Colbert MC, Hall DG, Kimball TR, Witt SA, Lorenz JN, Kirby ML, et al. Cardiac compartment-specific overexpression of a modified retinoic acid receptor produces dilated cardiomyopathy and congestive heart failure in transgenic mice. J Clin Invest. 1997;100:1958–1968
  22. Conduah Birt JE, Shuker DE, Farmer PB. Stable acetaldehyde–protein adducts as biomarkers of alcohol exposure. Chem Res Toxicol. 1998;11:136–142
  23. Constant J. The alcoholic cardiomyopathies—genuine and pseudo. Cardiology. 1999;91:92–95
  24. Cunningham CC, Bailey SM. Ethanol consumption and liver mitochondria function. Biol Signals Recept. 2001;10:271–282
  25. Duan J, Esberg LB, Ye G, Borgerding AJ, Ren BH, Aberle NS, et al. Influence of gender on ethanol-induced ventricular myocyte contractile depression in transgenic mice with cardiac overexpression of alcohol dehydrogenase. Comp Biochem Physiol A Mol Integr Physiol. 2003;134:607–614
  26. Duan J, McFadden GE, Borgerding AJ, Norby FL, Ren BH, Ye G, et al. Overexpression of alcohol dehydrogenase exacerbates ethanol-induced contractile defect in cardiac myocytes. Am J Physiol Heart Circ Physiol. 2002;282:H1216–H1222
  27. Edes I, Piros G, Forster T, Csanady M. Alcohol-induced congestive cardiomyopathy in adult turkeys: effects on myocardial antioxidant defence systems. Basic Res Cardiol. 1987;82:551–556
  28. Eriksson CJP. The role of acetaldehyde in the actions of alcohol (update 2000). Alcohol Clin Exp Res. 2001;25:15S–32S
  29. Eriksson CJP, Fukunaga T, Sarkola T, Lindholm H, Ahola L. Estrogen-related acetaldehyde elevation in women during alcohol intoxication. Alcohol Clin Exp Res. 1996;20:1192–1195
  30. Espinet C, Argiles JM. Ethanol and acetaldehyde concentrations in the rat foeto-maternal system after an acute ethanol administration given to the mother. Arch Int Physiol Biochim. 1984;92:339–344
  31. Estruch R, Nicolas JM, Villegas E, Junque A, Urbano-Marquez A. Relationship between ethanol-related diseases and nutritional status in chronically alcoholic men. Alcohol Alcohol. 1993;28:543–550
  32. Fang JL, Vaca CE. Detection of DNA adducts of acetaldehyde in peripheral white blood cells of alcohol abusers. Carcinogenesis. 1997;18:627–632
  33. Folden DV, Gupta A, Sharma AC, Li S-Y, Saari JT, Ren J. Malondialdehyde inhibits cardiac contractile function in ventricular myocytes via a p38 mitogen-activated protein kinase–dependent mechanism. Br J Pharmacol. 2003;139:1310–1316
  34. Gómez-Quiroz L, Bucio L, Souza V, Escobar C, Farfán B, Hernández E, et al. Interleukin 8 response and oxidative stress in HepG2 cells treated with ethanol, acetaldehyde or lipopolysaccharide. Hepatol Res. 2003;26:134–141
  35. Gonthier B, Jeunet A, Barret L. Electron spin resonance study of free radicals produced from ethanol and acetaldehyde after exposure to a Fenton system or to brain and liver microsomes. Alcohol. 1991;8:369–375
  36. Guerri C, Montoliu C, Renau-Piqueras J. Involvement of free radical mechanism in the toxic effects of alcohol: implications for fetal alcohol syndrome. Adv Exp Med Biol. 1994;366:291–305
  37. Hannuksela ML, Liisanantt MK, Savolainen MJ. Effect of alcohol on lipids and lipoproteins in relation to atherosclerosis. Crit Rev Clin Lab Sci. 2002;39:225–283
  38. Harcombe AA, Ramsay L, Kenna JG, Koskinas J, Why HJ, Richardson PJ, et al. Circulating antibodies to cardiac protein–acetaldehyde adducts in alcoholic heart muscle disease. Clin Sci (Lond). 1995;88:263–268
  39. Hashimoto Y, Nakayama T, Futamura A, Omura M, Nakarai H, Nakahara K. Relationship between genetic polymorphisms of alcohol-metabolizing enzymes and changes in risk factors for coronary heart disease associated with alcohol consumption. Clin Chem. 2002;48:1043–1048
  40. Heap L, Ward RJ, Abiaka C, Dexter D, Lawlor M, Pratt O, et al. The influence of brain acetaldehyde on oxidative status, dopamine metabolism and visual discrimination task. Biochem Pharmacol. 1995;50:263–270
  41. Hintz KK, Relling DP, Saari JT, Borgerding AJ, Duan J, Ren BH, et al. Cardiac overexpression of alcohol dehydrogenase exacerbates cardiac contractile dysfunction, lipid peroxidation, and protein damage after chronic ethanol ingestion. Alcohol Clin Exp Res. 2003;27:1090–1098
  42. Jänkälä H, Eklund KK, Kokkonen JO, Kovanen PT, Linstedt KA, Härkönen M, et al. Ethanol infusion increases ANP and p21 gene expression in isolated perfused rat heart. Biochem Biophys Res Commun. 2001;281:328–333
  43. Jänkälä H, Eriksson CJP, Eklund KK, Härkönen M, Mäki T. Combined calcium carbimide and ethanol treatment induces high blood acetaldehyde levels, myocardial apoptosis and altered expression of apoptosis-regulating genes in rat. Alcohol Alcohol. 2002;37:222–228
  44. Jänkälä H, Eriksson CJP, Petersen NE, Härkönen M, Mäki T. Role of acetaldehyde in the induction of heart left ventricular atrial natriuretic peptide gene expression in rats. Alcohol Alcohol. 2000;35:331–335
  45. Jeong K-S, Soh Y, Jeng J, Felder MR, Hardwick JP, Song BJ. Cytochrome P450 2E1 (CYP2E1)-dependent production of a 37-kDa acetaldehyde–protein adduct in the rat liver. Arch Biochem Biophys. 2000;384:81–87
  46. Kajander OA, Kupari M, Perola M, Pajarinen J, Savolainen V, Penttilä A, et al. Testing genetic susceptibility loci for alcoholic heart muscle disease. Alcohol Clin Exp Res. 2001;25:1409–1413
  47. Knecht KT, Adachi Y, Bradford BU, Iimuro Y, Kadiiska M, Xuang QH, et al. Free radical adducts in the bile of rats treated chronically with intragastric alcohol: inhibition by destruction of Kupffer cells. Mol Pharmacol. 1995;47:1028–1034
  48. Korsten MA, Matsuzaki S, Feinman L, Lieber CS. High blood acetaldehyde levels after ethanol administration. Difference between alcoholic and nonalcoholic subjects. N Engl J Med. 1975;292:386–389
  49. Lai C-L, Chao Y-C, Chen Y-C, Liao C-S, Chen M-C, Liu Y-C, et al. No sex and age influence on the expression pattern and activities of human gastric alcohol and aldehyde dehydrogenases. Alcohol Clin Exp Res. 2000;24:1625–1632
  50. Lange LG, Sobel BE. Mitochondrial dysfunction induced by fatty acid ethyl esters, myocardial metabolites of ethanol. J Clin Invest. 1983;72:724–731
  51. Lee YJ, Aroor AR, Shukla SD. Temporal activation of p42/44 mitogen-activated protein kinase and c-Jun N-terminal kinase by acetaldehyde in rat hepatocytes and its loss after chronic ethanol exposure. J Pharmacol Exp Ther. 2002;301:908–914
  52. Li S-Y, Gomelsky M, Duan J, Zhang Z, Gomelsky L, Zhang X, et al. Overexpression of aldehyde dehydrogenase-2 (ALDH2) transgene prevents acetaldehyde-induced cell injury in human umbilical vein endothelial cells: role of ERK and p38 mitogen-activated protein kinase. J Biol Chem. 2004;279:11244–11252
  53. Liang Q, Carlson EC, Borgerding AJ, Epstein PN. A transgenic model of acetaldehyde overproduction accelerates alcohol cardiomyopathy. J Pharmacol Exp Ther. 1999;291:766–772
  54. Lieber CS. Microsomal ethanol-oxidizing system (MEOS): the first 30 years (1968–1998)—a review. Alcohol Clin Exp Res. 1999;23:991–1007
  55. Lindros KO, Stowell A, Pikkarainen P, Salaspuro M. Elevated blood acetaldehyde in alcoholics with accelerated ethanol elimination. Pharmacol Biochem Behav 13 Suppl. 1980;1:119–124
  56. Lucey MR, Hill EM, Young JP, Demo-Dananberg L, Beresford TP. The influences of age and gender on blood ethanol concentrations in healthy humans. J Stud Alcohol. 1999;60:103–110
  57. Mantle D, Preedy VR. Free radicals as mediators of alcohol toxicity. Adverse Drug React Toxicol Rev. 1999;18:235–252
  58. Masamune A, Kikuta K, Satoh M, Satoh A, Shimosegawa T. Alcohol activates activator protein-1 and mitogen-activated protein kinases in rat pancreatic stellate cells. J Pharmacol Exp Ther. 2002;302:36–42
  59. McDonough KH. The role of alcohol in the oxidant antioxidant balance in heart. Front Biosci. 1999;4:d601–d606
  60. Morales JA, Ram JL, Song J, Brown RA. Acetaldehyde inhibits current through voltage-dependent calcium channels. Toxicol Appl Pharmacol. 1997;143:70–74
  61. Nakano M, Kikuyama M, Hasegawa T, Ito T, Sakurai K, Hiraishi K, et al. The first observation of O2− generation at real time in vivo from non-Kupffer sinusoidal cells in perfused rat liver during acute ethanol intoxication. FEBS Lett. 1995;372:140–143
  62. Nakao LS, Kadiiska MB, Mason RP, Grijalba MT, Augusto O. Metabolism of acetaldehyde to methyl and acetyl radicals: in vitro and in vivo electron paramagnetic resonance spin-trapping studies. Free Radic Biol Med. 2000;29:721–729
  63. Napoli C, de Nigris F, Palinski W. Multiple role of reactive oxygen species in the arterial wall. J Cell Biochem. 2001;82:674–682
  64. Niemelä O. Aldehyde–protein adducts in the liver as a result of ethanol-induced oxidative stress. Front Biosci. 1999;4:d506–d513
  65. Niemelä O. Distribution of ethanol-induced protein adducts in vivo: relationship to tissue injury. Free Radic Biol Med. 2001;31:1533–1538
  66. Nishimura FT, Fukunaga T, Kajiura H, Umeno K, Takakura H, Ono T, et al. Effects of aldehyde dehydrogenase-2 genotype on cardiovascular and endocrine responses to alcohol in young Japanese subjects. Auton Neurosci. 2002;102:60–70
  67. Nuutinen H, Lindros KO, Salaspuro M. Determinants of blood acetaldehyde level during ethanol oxidation in chronic alcoholics. Alcohol Clin Exp Res. 1983;7:163–168
  68. Oei HH, Zoganas HC, McCord JM, Schaffer SW. Role of acetaldehyde and xanthine oxidase in ethanol-induced oxidative stress. Res Commun Chem Pathol Pharmacol. 1986;51:195–203
  69. Parola M, Robino G, Marra F, Pinzani M, Bellomo G, Leonarduzzi G, et al. HNE interacts directly with JNK isoforms in human hepatic stellate cells. J Clin Invest. 1998;102:1942–1950
  70. Patel VB, Ajmal R, Sherwood RA, Sullivan A, Richardson PJ, Preedy VR. Cardioprotective effect of propranolol from alcohol-induced heart muscle damage as assessed by plasma cardiac troponin-T. Alcohol Clin Exp Res. 2001;25:882–889
  71. Patel VB, Why HJ, Richardson PJ, Preedy VR. The effects of alcohol on the heart. Adverse Drug React Toxicol Rev. 1997;16:15–43
  72. Peng GS, Wang MF, Chen CY, Luu SU, Chou HC, Li T-K, et al. Involvement of acetaldehyde for full protection against alcoholism by homozygosity of the variant allele of mitochondrial aldehyde dehydrogenase gene in Asians. Pharmacogenetics. 1999;9:463–476
  73. Peng GS, Yin JH, Wang MF, Lee JT, Hsu YD, Yin SJ. Alcohol sensitivity in Taiwanese men with different alcohol and aldehyde dehydrogenase genotypes. J Formos Med Assoc. 2002;101:769–774
  74. Piano MR. Effects of gender on alcohol's heart dysfunction. In:  Watson RR,  Myers AK editor. Alcohol and Heart Disease. New York: Taylor & Francis; 2002;p. 28–47
  75. Preedy VR, Adachi J, Asano M, Koll M, Mantle D, Niemelä O, et al. Free radicals in alcoholic myopathy: indices of damage and preventive studies. Free Radic Biol Med. 2002;32:683–687
  76. Preedy VR, Adachi J, Peters TJ, Worrall S, Parkkila S, Niemelä O, et al. Recent advances in the pathology of alcoholic myopathy. Alcohol Clin Exp Res. 2001;25:54S–59S
  77. Rajasinghe H, Jayatilleke E, Shaw S. DNA cleavage during ethanol metabolism: role of superoxide radicals and catalytic iron. Life Sci. 1990;47:807–814
  78. Rao DN, Yang MX, Lasker JM, Cederbaum AI. 1-Hydroxyethyl radical formation during NADPH- and NADH-dependent oxidation of ethanol by human liver microsomes. Mol Pharmacol. 1996;49:814–821
  79. Ren J, Davidoff AJ, Brown RA. Acetaldehyde depresses shortening and intracellular Ca2+ transients in adult rat ventricular myocytes. Cell Mol Biol (Noisy-le-grand). 1997;43:825–834
  80. Ren J, Natavio M, Jefferson L, Pavlik ML, Brown RA. Loss of cardiac contractile response to tetrahydropapaveroline with advanced age and hypertension. Cell Mol Biol (Noisy-le-grand). 2001;47:OL15–OL22 Online Pub
  81. Richardson PJ, Patel VB, Preedy VR. Alcohol and the myocardium. Novartis Found Symp. 1998;216:35–45
  82. Ruef J, Rao GN, Li F, Bode C, Patterson C, Bhatnagar A, et al. Induction of rat aortic smooth muscle cell growth by the lipid peroxidation product 4-hydroxy-2-nonenal. Circulation. 1998;97:1071–1078
  83. Savage AO, Dunbar JC, Brown RA. Effects of acetaldehyde on the isolated papillary muscle of diabetic rats. J Cardiovasc Pharmacol. 1995;26:251–258
  84. Schoppet M, Maisch B. Alcohol and the heart. Herz. 2001;26:345–352
  85. Siddiq T, Richardson PJ, Mitchell WD, Teare J, Preedy VR. Ethanol-induced inhibition of ventricular protein synthesis in vivo and the possible role of acetaldehyde. Cell Biochem Funct. 1993;11:45–54
  86. Spies CD, Sander M, Stangl K, Fernandez-Sola J, Preedy VR, Rubin E, et al. Effects of alcohol on the heart. Curr Opin Crit Care. 2001;7:337–343
  87. Svegliati-Baroni G, Ridolfi F, Di Sario A, Saccomanno S, Bendia E, Benedetti A, et al. Intracellular signaling path-ways involved in acetaldehyde-induced collagen and fibronectin gene expression in human hepatic stellate cells. Hepatology. 2001;33:1130–1140
  88. Tanaka K, Honda M, Takabatake T. Redox regulation of MAPK pathways and cardiac hypertrophy in adult rat cardiac myocyte. J Am Coll Cardiol. 2001;37:676–685
  89. Tsukamoto S, Muto T, Nagoya T, Shimamura M, Saito M, Tainaka H. Determinations of ethanol, acetaldehyde and acetate in blood and urine during alcohol oxidation in man. Alcohol Alcohol. 1989;24:101–108
  90. Uchida K. Role of reactive aldehyde in cardiovascular diseases. Free Radic Biol Med. 2000;28:1685–1696
  91. Uchida K, Shiraishi M, Naito Y, Torii Y, Nakamura Y, Osawa T. Activation of stress signaling pathways by the end product of lipid peroxidation. 4-hydroxy-2-nonenal is a potential inducer of intracellular peroxide production. J Biol Chem. 1999;274:2234–2242
  92. Vendemiale G, Grattagliano I, Altomare E, Serviddio G, Portincasa P, Prigigallo F, et al. Mitochondrial oxidative damage and myocardial fibrosis in rats chronically intoxicated with moderate doses of ethanol. Toxicol Lett. 2001;123:209–216
  93. Watanabe A, Kobayashi M, Hobara N, Nakatsukasa H, Nagashima H, Fujimoto A. A report of unusually high blood ethanol and acetaldehyde levels in two surviving patients. Alcohol Clin Exp Res. 1985;9:14–16
  94. Weng Y-I, Shukla SD. Ethanol alters angiotensin II stimulated mitogen activated protein kinase in hepatocytes: agonist selectivity and ethanol metabolic independence. Eur J Pharmacol. 2000;398:323–331
  95. Worrall S, Niemelä O, Parkkila S, Peters TJ, Preedy VR. Protein adducts in type I and type II fibre predominant muscles of the ethanol-fed rat: preferential localisation in the sarcolemmal and subsarcolemmal region. Eur J Clin Invest. 2001;31:723–730
  96. Wu C-F, Bishopric NH, Pratt RE. Atrial natriuretic peptide induces apoptosis in neonatal rat cardiac myocytes. J Biol Chem. 1997;272:14860–14866
  97. Yoon S-O, Yun C-H, Chung A-S. Dose effect of oxidative stress on signal transduction in aging. Mech Ageing Dev. 2002;123:1597–1604
  98. Yoshida A. Molecular genetics of human aldehyde dehydrogenase. Pharmacogenetics. 1992;2:139–147
  99. Zhang X, Klein AL, Alberle NS, Norby FL, Ren BH, Duan J, et al. Cardiac-specific overexpression of catalase rescues ventricular myocytes from ethanol-induced cardiac contractile defect. J Mol Cell Cardiol. 2003;35:645–652
  100. Zima T, Fialova L, Mestek O, Janebova M, Crkovska J, Malbohan I, et al. Oxidative stress, metabolism of ethanol and alcohol-related diseases. J Biomed Sci. 2001;8:59–70

PII: S0741-8329(04)00049-7

doi: 10.1016/j.alcohol.2004.01.005

Alcohol
Volume 32, Issue 3 , Pages 175-186 , April 2004

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