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Adverse Effects of Chronic Alcohol Consumption

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Abstract

Chronic alcohol consumption has emerged as a leading cause of metabolic derangement in susceptible cohorts worldwide; ethanol has a high calorific value and excessive intake interferes with energy metabolism. It has a very high glycemic index, so the glucose homeostasis does not follow the normal physiological regulations in chronic consumption of ethanol. Chronic alcohol consumption is a global concern for its health issues. The detailed mechanism of alcohol-associated organ damage and health anomalies has been reviewed here. Almost all of its metabolic fates has minor to major impacts on any physiological process. The main rate-limiting markers of glucose homeostasis, i.e. NADH/NAD+ and ATP/ADP, are physiologically misjudged in ethanol consumption; as a result, excess acetoacetyl CoA becomes engaged in ketone body formation resulting in ketoacidosis. Ethanol induced ROS production and antioxidant depletion resulting in necrotic tissue damage especially in the stomach, intestine epithelial cells, and liver. Increased oxidative stress causes vascular dysfunction, NO deregulation, peripheral vascular resistance, increased blood pressure, and aldosterone-induced hypertension. Ethanol manipulates intracellular phosphorylation regulations by influencing MAPK and inflammatory molecule, like TNFa and IL-6, and transcriptional stress factor like NF-κβ, Nrf-2, and Hif-α via redox signalling. Activation of lipogenic factors and PPAR signalling drastically increase body fat accumulation. Direct damage to the pancreatic cells generates insulin resistance. Synergistic effects of several metabolic malfunctioning develop insulin resistance, chronic hyperglycaemia, and abnormal fat accumulation.

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References

  1. Wan Q, Liu Y, Guan Q, Gao L, Lee KO, Zhao J. Ethanol feeding impairs insulin-stimulated glucose uptake in isolated rat skeletal muscle: role of Gs alpha and cAMP. Alcohol Clin Exp Res. 2005;29:1450–6.

    Article  CAS  Google Scholar 

  2. Wei M, Gibbons LW, Mitchell TL, Kampert JB, Blair SN. Alcohol intake and incidence of type 2 diabetes in men. Diabetes Care. 2000;23:18–22.

    Article  CAS  Google Scholar 

  3. Dillon ES, Dyer WW, Smelo LS. Ketone acidosis of non-diabetic adults. Med Clin N Am. 1940;24:1813–22.

    Article  Google Scholar 

  4. Umpierrez GE, Digirolamo M, Tuvlin JA, et al. Differences in metabolic and hormonal milieu in diabetic and alcohol-induced ketoacidosis. J Crit Care. 2000;15:52–9.

    Article  CAS  Google Scholar 

  5. McGuire LC, Cruickshank AM, Munro PT. Alcoholic ketoacidosis. Emerg Med J. 2006;23:417–20. https://doi.org/10.1136/emj.2004.017590.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Lefevre A, Adler H, Lieber CS. Effect of ethanol on ketone metabolism. J Clin Invest. 1970;49:1775–82.

    Article  CAS  Google Scholar 

  7. Das SK, Vasudevan DM. Effect of ethanol on liver antioxidant defense systems: a dose dependent study. Indian J Clin Biochem. 2005;20:80–4.

    Article  CAS  Google Scholar 

  8. Gongora MC, Qin Z, Laude K, Kim HW, McCann L, Folz JR, et al. Role of extracellular superoxide dismutase in hypertension. Hypertension. 2006;48:473–81. https://doi.org/10.1161/01.HYP.0000235682.47673.ab.

    Article  CAS  PubMed  Google Scholar 

  9. Tajima M, Kurashima Y, Sugiyama K, Ogura T, Sakagami H. The redox state of glutathione regulates the hypoxic induction of HIF-1. Eur J Pharmacol. 2009;606:45–9. https://doi.org/10.1016/j.ejphar.2009.01.026.

    Article  CAS  PubMed  Google Scholar 

  10. Husain K, Scott BR, Reddy SK, Somani SM. Chronic ethanol and nicotine interaction on rat tissue antioxidant defense system. Alcohol. 2001;25:89–97. https://doi.org/10.1016/S0741-8329(01)00176-8.

    Article  CAS  PubMed  Google Scholar 

  11. Pigeolet E, Corbisier P, Houbion A, Lambert D, Michiels C, Raes M, et al. Glutathione peroxidase, superoxide dismutase, and catalase inactivation by peroxides and oxygen derived free radicals. Mech Ageing Dev. 1990;51:283–97. https://doi.org/10.1016/0047-6374(90)90078-T.

    Article  CAS  PubMed  Google Scholar 

  12. Dinu D, Nechifor MT, Movileanu L. Ethanol-induced alterations of the antioxidant defense system in rat kidney. J Biochem Mol Toxicol. 2005;19:386–95. https://doi.org/10.1002/jbt.20101.

    Article  CAS  PubMed  Google Scholar 

  13. Husain K, Mejia J, Lalla J. Physiological basis for effect of physical conditioning on chronic ethanol-induced hypertension in a rat model. Mol Cell Biochem. 2006;289:175–83. https://doi.org/10.1007/s11010-006-9161-3.

    Article  CAS  PubMed  Google Scholar 

  14. Ibsen H, Christensen NJ, Rasmussen S, Hollnagel H, Damkjaer Nielsen M, Giese J. The influence of chronic high alcohol intake on blood pressure, plasma noradrenaline concentration and plasma renin concentration. Clin Sci (Lond). 1981;61(Suppl):377s–9s.

    Article  CAS  Google Scholar 

  15. Puddey IB, Vandongen R, Beilin LJ, Rouse IL. Alcohol stimulation of renin release in man: its relation to the hemodynamic, electrolyte, and sympatho-adrenal responses to drinking. J Clin Endocrinol Metab. 1985;61:37–42. https://doi.org/10.1210/jcem-61-1-37.

    Article  CAS  PubMed  Google Scholar 

  16. Nieminen MM. Renin-aldosterone axis in ethanol intoxication during sodium and fluid repletion versus depletion. Int J Clin Pharmacol TherToxicol. 1983;21:552–7.

    CAS  Google Scholar 

  17. Arkwright PD, Beilin LJ, Vandongen R, Rouse IA, Lalor C. The pressor effect of moderate alcohol consumption in man: a search for mechanisms. Circulation. 1982;66:515–9. https://doi.org/10.1161/01.CIR.66.3.515.

    Article  CAS  PubMed  Google Scholar 

  18. Russ R, Abdel-Rahman AR, Wooles WR. Role of the sympathetic nervous system in ethanol-induced hypertension in rats. Alcohol. 1991;8:301–7. https://doi.org/10.1016/0741-8329(91)90433-W.

    Article  CAS  PubMed  Google Scholar 

  19. Chan TC, Sutter MC. Ethanol consumption and blood pressure. Life Sci. 1983;33:1965–73. https://doi.org/10.1016/0024-3205(83)90734-8.

    Article  CAS  PubMed  Google Scholar 

  20. Hussa RO. Immunologic and physical characterization of human chorionic gonadotropin and its subunits in cultures of human malignant trophoblast. J Clin Endocrinol Metab. 1977;44:1154–62. https://doi.org/10.1161/01.HYP.19.2.175.

    Article  CAS  PubMed  Google Scholar 

  21. Husain K, Vazquez M, Ansari RA, Malafa MP, Lalla J. Chronic alcohol-induced oxidative endothelial injury relates to angiotensin II levels in the rat. Mol Cell Biochem. 2008;307:51–8. https://doi.org/10.1007/s11010-007-9583-6.

    Article  CAS  PubMed  Google Scholar 

  22. Wright JW, Morseth SL, Abhold RH, Harding JW. Elevations in plasma angiotensin II with prolonged ethanol treatment in rats. Pharmacol Biochem Behav. 1986;24:813–8. https://doi.org/10.1016/0091-3057(86)90416-8.

    Article  CAS  PubMed  Google Scholar 

  23. Okuno F, Arai M, Ishii H, Shigeta Y, Ebihara Y, Takagi S, et al. Mild but prolonged elevation of serum angiotensin converting enzyme (ACE) activity in alcoholics. Alcohol. 1986;3:357–9. https://doi.org/10.1016/0741-8329(86)90053-4.

    Article  CAS  PubMed  Google Scholar 

  24. Husain K, Ansari RA, Ferder L. Alcohol-induced hypertension: mechanism and prevention. World J Cardiol. 2014;6(5):245–52 ISSN 1949–8462. https://doi.org/10.4330/wjc.v6.i5.245.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288:373–6. https://doi.org/10.1038/288373a0.

    Article  CAS  PubMed  Google Scholar 

  26. Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987;327:524–6. https://doi.org/10.1038/327524a0.

    Article  CAS  PubMed  Google Scholar 

  27. Ignarro LJ, Byrns RE, Buga GM, Wood KS. Endothelium derived relaxing factor from pulmonary artery and vein possesses pharmacologic and chemical properties identical to those of nitric oxide radical. Circ Res. 1987;61:866–79. https://doi.org/10.1161/01.RES.61.6.866.

    Article  CAS  PubMed  Google Scholar 

  28. Thorand B, Baumert J, Döring A, Schneider A, Chambless L, Löwel H, et al. Association of cardiovascular risk factors with markers of endothelial dysfunction in middle-aged men and women. Results from the MONICA/ KORA Augsburg Study. Thromb Haemost. 2006;95:134–41.

    Article  CAS  Google Scholar 

  29. Villanueva C, Giulivi C. Subcellular and cellular locations of nitric oxide synthase isoforms as determinants of health and disease. Free Radic Biol Med. 2010;49:307–16. https://doi.org/10.1016/j.freeradbiomed.2010.04.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Tirapelli CR, Fukada SY, Yogi A, Chignalia AZ, Tostes RC, Bonaventura D, et al. Gender-specific vascular effects elicited by chronic ethanol consumption in rats: a role for inducible nitric oxide synthase. Br J Pharmacol. 2008;153:468–79. https://doi.org/10.1038/sj.bjp.0707589.

    Article  CAS  PubMed  Google Scholar 

  31. Krecsmarik M, Izbéki F, Bagyánszki M, Linke N, Bódi N, Kaszaki J, et al. Chronic ethanol exposure impairs neuronal nitric oxide synthase in the rat intestine. Alcohol Clin Exp Res. 2006;30:967–73. https://doi.org/10.1111/j.1530-0277.2006.00110.x.

    Article  CAS  PubMed  Google Scholar 

  32. Marchi KC, Muniz JJ, Tirapelli CR. Hypertension and chronic ethanol consumption: what do we know after a century of study? World J Cardiol. 2014;6(5):283–94 ISSN 1949–8462. https://doi.org/10.4330/wjc.v6.i5.283.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Griendling KK, Sorescu D, Ushio-Fukai M. NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res. 2000;86:494–501. https://doi.org/10.1161/01.RES.86.5.494.

    Article  CAS  PubMed  Google Scholar 

  34. Fukui T, Ishizaka N, Rajagopalan S, Laursen JB, Capers Q, Taylor WR, et al. p22phox mRNA expression and NADPH oxidase activity are increased in aortas from hypertensive rats. Circ Res. 1997;80:45–51. https://doi.org/10.1161/01.RES.80.1.45.

    Article  CAS  PubMed  Google Scholar 

  35. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA. 1990;87:1620–4. https://doi.org/10.1073/pnas.87.4.1620.

    Article  CAS  PubMed  Google Scholar 

  36. Husain K, Ferder L, Ansari RA, Lalla J. Chronic ethanol ingestion induces aortic inflammation/oxidative endothelial injury and hypertension in rats. Hum Exp Toxicol. 2011;30:930–9. https://doi.org/10.1177/0960327110384520.

    Article  CAS  PubMed  Google Scholar 

  37. Johnson RA, Freeman RH. Sustained hypertension in the rat induced by chronic blockade of nitric oxide production. Am J Hypertens. 1992;5:919–22.

    Article  CAS  Google Scholar 

  38. Husain K. Physical conditioning modulates rat cardiac vascular endothelial growth factor gene expression in nitric oxide deficient hypertension. Biochem Biophys Res Commun. 2004;320:1169–74. https://doi.org/10.1016/j.bbrc.2004.06.058.

    Article  CAS  PubMed  Google Scholar 

  39. Husain K, Mejia J, Lalla J, Kazim S. Dose response of alcohol-induced changes in BP, nitric oxide and antioxidants in rat plasma. Pharmacol Res. 2005;51:337–43. https://doi.org/10.1016/j.phrs.2004.10.005.

    Article  CAS  PubMed  Google Scholar 

  40. Husain K, Vazquez-Ortiz M, Lalla J. Down-regulation of ventricular nitric oxide generating system in chronic alcohol treated hypertensive rats. Cell Mol Biol(Noisy-le-grand). 2007;53:32–7.

    CAS  Google Scholar 

  41. Husain K. Vascular endothelial oxidative stress in alcohol induced hypertension. Cell Mol Biol(Noisy-le-grand). 2007;53:70–7.

    CAS  Google Scholar 

  42. Husain K, Vazquez-Ortiz M, Lalla J. Down regulation of aortic nitric oxide and antioxidant systems in chronic alcohol-induced hypertension in rats. Hum Exp Toxicol. 2007;26:427–34. https://doi.org/10.1177/0960327106072993.

    Article  CAS  PubMed  Google Scholar 

  43. Ansari RA, Husain K, Rizvi SAA. Role of transcription factors in steatohepatitis and hypertension after ethanol: the epicenter of metabolism. Biomolecules. 2016;6:29. https://doi.org/10.3390/biom6030029.

    Article  CAS  PubMed Central  Google Scholar 

  44. Ohnishi H, Miyata T, Yasuda H, Satoh Y, Hanatsuka K, Kita H, et al. Distinct roles of Smad2-, Smad3-, and ERK-dependent pathways in transforming growth factor-beta1 regulation of pancreatic stellate cellular functions. J Biol Chem. 2004;279:8873–8. https://doi.org/10.1074/jbc.M309698200.

    Article  CAS  PubMed  Google Scholar 

  45. Aoki H, Ohnishi H, Hama K, Ishijima T, Satoh Y, Hanatsuka K, et al. Autocrine loop between TGF-beta1 and IL-1beta through Smad3- and ERK dependent pathways in rat pancreatic stellate cells. Am J Physiol Cell Physiol. 2006;290:C1100–8. https://doi.org/10.1152/ajpcell.00465.2005.

    Article  CAS  PubMed  Google Scholar 

  46. Massagué J, Wotton D. Transcriptional control by the TGF-beta/Smadsignaling system. EMBO J. 2000;19:1745–54. https://doi.org/10.1093/emboj/19.8.1745.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Wakefield LM, Roberts AB. TGF-beta signaling: positive and negative effects on tumorigenesis. Curr Opin Genet Dev. 2002;12:22–9.

    Article  CAS  Google Scholar 

  48. Nicolás FJ, Hill CS. Attenuation of the TGF-beta-Smad signalling pathway in pancreatic tumor cells confers resistance to TGF-betainduced growth arrest. Oncogene. 2003;22:3698–711. https://doi.org/10.1038/sj.onc.1206420.

    Article  CAS  PubMed  Google Scholar 

  49. Chang L, Karin M. Mammalian MAP kinase signalling cascades. Nature. 2001;410:37–40. https://doi.org/10.1038/35065000.

    Article  CAS  PubMed  Google Scholar 

  50. 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.

    Article  CAS  Google Scholar 

  51. McCarroll JA, Phillips PA, Park S, Doherty E, Pirola RC, Wilson JS, et al. Pancreatic stellate cell activation by ethanol and acetaldehyde: is it mediated by the mitogen-activated protein kinase signaling pathway? Pancreas. 2003;27:150–60.

    Article  CAS  Google Scholar 

  52. Lesina M, Wörmann SM, Neuhöfer P, Song L, Algül H. Interleukin-6 in inflammatory and malignant diseases of the pancreas. Semin Immunol. 2014;26:80–7. https://doi.org/10.1016/j.smim.2014.01.002.

    Article  CAS  PubMed  Google Scholar 

  53. Polsky S, Akturk HK. Alcohol consumption, diabetes risk, and cardiovascular disease within diabetes. Curr Diab Rep. 2017;17(12):136. https://doi.org/10.1007/s11892-017-0950-8.

    Article  PubMed  Google Scholar 

  54. Knott C, Bell S, Britton A. Alcohol consumption and the risk of type 2 diabetes: a systematic review and dose-response meta-analysis of more than 1.9 million individuals from 38 observational studies. Diabetes Care. 2015;38(9):1804–12. https://doi.org/10.2337/dc15-0710.

    Article  CAS  PubMed  Google Scholar 

  55. Li XH, Yu FF, Zhou YH, He J. Association between alcohol consumption and the risk of incident type 2 diabetes: a systematic review and dose-response meta-analysis. Am J Clin Nutr. 2016;103(3):818–29. https://doi.org/10.3945/ajcn.115.114389.

    Article  CAS  PubMed  Google Scholar 

  56. Pandey S. Healthy controls in nonalcoholic fatty liver disease management: a biomedical research perspective. Hepatology. 2017;66(3):1006–7. https://doi.org/10.1002/hep.29334.

    Article  PubMed  Google Scholar 

  57. Elgendy R, Deschênes SS, Burns RJ, Schmitz N. Do mental disorders moderate the association between diabetes status and alcohol consumption? Psychol Health Med. 2018;23(3):277–84. https://doi.org/10.1080/13548506.2017.1384552.

    Article  PubMed  Google Scholar 

  58. Pandey S. Letter to editor: chronic alcohol exposure alters circulating insulin and ghrelin levels in hepatic steatosis: a translational research perspective. Am J Physiol Gastrointest Liver Physiol. 2019;317(3):G359–60. https://doi.org/10.1152/ajpgi.00102.2019.

    Article  CAS  PubMed  Google Scholar 

  59. Bhattacharya S, Ghosh R, Maiti S, Khan GA, Sinha AK. The activation by glucose of liver membrane nitric oxide synthase in the synthesis and translocation of glucose transporter-4 in the production of insulin in the mice hepatocytes. PLoS One. 2013;8(12):e81935. https://doi.org/10.1371/journal.pone.0081935.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Bhattacharya S, Maji U, Khan GA, Das R, Sinha AK, Ghosh C, et al. Antidiabetic role of a novel protein from garlic via NO in expression of Glut-4/insulin in liver of alloxan induced diabetic mice. Biomed Pharmacother. 2019;111:1302–14. https://doi.org/10.1016/j.biopha.2019.01.036.

    Article  CAS  PubMed  Google Scholar 

  61. Shen C, Wang C, Han S, Wang Z, Dong Z, Zhao X, et al. Aldehyde dehydrogenase 2 deficiency negates chronic low-to-moderate alcohol consumption-induced cardioprotecion possibly via ROS-dependent apoptosis and RIP1/RIP3/MLKL-mediated necroptosis. Biochim Biophys Acta Mol basis Dis. 2017;1863(8):1912–8.

    Article  CAS  Google Scholar 

  62. Feng HY, Chen YC. Role of bile acids in carcinogenesis of pancreatic cancer: an old topic with new perspective. World J Gastroenterol. 2016;22(33):7463–77. https://doi.org/10.3748/wjg.v22.i33.7463.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Shi J, Xue J. Inflammation and development of pancreatic ductal adenocarcinoma. Chin Clin Oncol. 2019;8(2):19. https://doi.org/10.21037/cco.2019.04.02.

    Article  PubMed  Google Scholar 

  64. Yan X, Wu L, Lin Q, Dai X, Hu H, Wang K, et al. From the cover: alcohol inhibition of the enzymatic activity of glyceraldehyde 3-phosphate dehydrogenase impairs cardiac glucose utilization, Contributing to alcoholic cardiomyopathy. Toxicol Sci. 2017;159(2):392–401. https://doi.org/10.1093/toxsci/kfx140.

    Article  CAS  PubMed  Google Scholar 

  65. Zhu L, Rossi M, Cui Y, Lee RJ, Sakamoto W, Perry NA, et al. Hepatic β-arrestin 2 is essential for maintaining euglycemia. J Clin Invest. 2017;127(8):2941–5. https://doi.org/10.1172/JCI92913.

    Article  PubMed  PubMed Central  Google Scholar 

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  1. Department of Biochemistry, Cell & Molecular Therapeutics Laboratory, Oriental Institute of Science and Technology, Rangamati, Midnapore, WB, 721102, India

    Suchismita Mukharjee & Smarajit Maiti

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Initial draft preparation and diagram preparation: SuM; conceptual basis, diagram designing, and final approval: SM; manuscript review: both authors.

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Mukharjee, S., Maiti, S. Adverse Effects of Chronic Alcohol Consumption. SN Compr. Clin. Med. 2, 308–315 (2020). https://doi.org/10.1007/s42399-020-00237-9

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