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Dual effect of red wine on liver redox status: a concise and mechanistic review

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Abstract

Chronic ethanol consumption is a strong risk factor for the development of liver disease. Multiple mechanisms are involved in ethanol-mediated liver injury; oxidative stress being pointed has an important factor. However, it should be noted that moderate consumption of red wine has been associated with hepatoprotective effects, mainly due to the antioxidant effect of resveratrol, one of its polyphenolic compounds. In this paper, the potential molecular mechanisms through which the protective effects of resveratrol counteract the oxidative effect of ethanol and the way as this dual effect impacts liver oxidative stress are reviewed. Mechanistic evaluation of modulation of oxidative signaling pathways by ethanol and resveratrol may explain the pathogenesis of various liver diseases and ultimately to disclose possible pharmacological therapies.

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References

  • Ahmad A, Ahmad R (2014) Resveratrol mitigate structural changes and hepatic stellate cell activation in N’-nitrosodimethylamine-induced liver fibrosis via restraining oxidative damage. Chem Biol Interact 221:1–12. doi:10.1016/j.cbi.2014.07.007

    Article  CAS  PubMed  Google Scholar 

  • Ajakaiye M, Jacob A, Wu R, Nicastro JM, Coppa GF, Wang P (2011) Alcohol and hepatocyte-Kupffer cell interaction. Mol Med Rep 4:597–602. doi:10.3892/mmr.2011.471

    CAS  PubMed  Google Scholar 

  • Ajmo JM, Liang X, Rogers CQ, Pennock B, You M (2008) Resveratrol alleviates alcoholic fatty liver in mice. Am J Physiol Gastrointest Liver Physiol 295:833–842. doi:10.1152/ajpgi.90358.2008

    Article  CAS  Google Scholar 

  • Albano E, French SW, Ingelman-Sundberg M (1999) Hydroxyethyl radicals in ethanol hepatotoxicity. Front Biosci 4:533–540

    Article  Google Scholar 

  • Andrukhiv A, Costa AD, West IC, Garlid KD (2006) Opening mitoKATP increases superoxide generation from complex I of the electron transport chain. Am J Physiol Heart Circ Physiol 291:2067–2074. doi:10.1152/ajpheart.00272.2006

    Article  CAS  Google Scholar 

  • Apostolou A, Stagos D, Galitsiou E, Spyrou A, Haroutounian S, Portesis N, Trizoglou I, Wallace Hayes A, Tsatsakis AM, Kouretas D (2013) Assessment of polyphenolic content, antioxidant activity, protection against ROS-induced DNA damage and anticancer activity of Vitis vinifera stem extracts. Food Chem Toxicol 61:60–68. doi:10.1016/j.fct.2013.01.029

    Article  CAS  PubMed  Google Scholar 

  • Arteel GE, Raleigh JA, Bradford BU, Thurman RG (1996) Acute alcohol produces hypoxia directly in rat liver tissue in vivo: role of Kupffer cells. Am J Physiol 271:494–500

    Google Scholar 

  • Bastianetto S, Ménard C, Quirion R (2014) Neuroprotective action of resveratrol. Biochim Biophys Acta. doi:10.1016/j.bbadis.2014.09.011

    PubMed  Google Scholar 

  • Bautista AP (1997) Chronic alcohol intoxication induces hepatic injury through enhanced macrophage inflammatory protein-2 production and intercellular adhesion molecule-1 expression in the liver. Hepatology 25(2):335–342. doi:10.1002/hep.510250214

    Article  CAS  PubMed  Google Scholar 

  • Becker U, Deis A, Sorensen TI, Grønbaek M, Borch-Johnsen K, Müller CF, Schnohr P, Jensen G (1996) Prediction of risk of liver disease by alcohol intake, sex, and age: a prospective population study. Hepatology 23:1025–1029. doi:10.1002/hep.510230513

    Article  CAS  PubMed  Google Scholar 

  • Becker U, Gronbaek M, Johansen D, Sorensen TI (2002) Lower risk for alcohol induced cirrhosis in wine drinkers. Hepatology 35:808–875. doi:10.1053/jhep.2002.32101

    Article  Google Scholar 

  • Beier JI, McClain CJ (2010) Mechanisms and cell signaling in alcoholic liver disease. Biol Chem 391:1249–1264. doi:10.1515/BC.2010.137

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bertelli AAE, Giovannini L, Stradi R, Bertelli A, Tillement JP (1996) Plasma, urine and tissue levels of trans- and cis-resveratrol (3,40,5-trihydroxystilbene) after short-term or prolonged administration of red wine to rats. Int J Tissue React 18(2–3):67–71

    CAS  PubMed  Google Scholar 

  • Bertelli A, Bertelli AAE, Gozzini A, Giovannini L (1998) Plasma and tissue resveratrol concentrations and pharmacological activity. Drugs Exp Clin Res 24:133–138

    CAS  PubMed  Google Scholar 

  • Bishayee A, Darvesh AS, Politis T, McGory R (2010) Resveratrol and liver disease: from bench to bedside and community. Liver Int 30:1103–1114. doi:10.1111/j.1478-3231.2010.02295.x

    Article  CAS  PubMed  Google Scholar 

  • Bjørneboe G-EA, Bjørneboe A, Hagen BF, Mørland J, Drevon CA (1987) Reduced hepatic α-tocopherol content after long-term administration of ethanol to rats. Biochim Biophys Acta 918:236–241

    Article  PubMed  Google Scholar 

  • Blouin J, Peynaud É (2012) Connaissance et travail du vin-5e édition. Dunod

  • Bode C, Bode JC (2003) Effect of alcohol consumption on the gut. Best Pract Res Clin Gastroenterol 17:575–592. doi:10.1016/S1521-6918(03)00034-9

    Article  CAS  PubMed  Google Scholar 

  • Bugianesi E, McCullough AJ, Marchesini G (2005) Insulin resistance: a metabolic pathway to chronic liver disease. Hepatology 42:978–1000. doi:10.1002/hep.20920

    Article  CAS  Google Scholar 

  • Bujanda L, Hijona E, Larzabal M, Beraza M, Aldazabal P, García-Urkia N, Sarasqueta C, Cosme A, Irastorza B, González A, Arenas JI Jr (2008) Resveratrol inhibits nonalcoholic fatty liver disease in rats. BMC Gastroenterol 8:40. doi:10.1186/1471-230X-8-40

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Byun JS, Suh YG, Yi HS, Lee YS, Jeong WI (2013) Activation of toll-like receptor 3 attenuates alcoholic liver injury by stimulating Kupffer cells and stellate cells to produce interleukin-10 in mice. J Hepatol 58:342–349. doi:10.1016/j.jhep.2012.09.016

    Article  CAS  PubMed  Google Scholar 

  • Cai YJ, Fang JG, Ma LP, Yang L, Liu ZL (2003) Inhibition of free radical-induced peroxidation of rat liver microsomes by resveratrol and its analogues. Biochim Biophys Acta 1637:31–38. doi:10.1016/S0925-4439(02)00174-6

    Article  CAS  PubMed  Google Scholar 

  • Carando S, Teissedre PL, Waffo-Teguo P, Cabanis JC, Deffieux G, Merillon JM (1999) High–performance liquid chromatography coupled with fluorescence detection for the determination of trans–astringin in wine. J Chromatogr A 849:617–620. doi:10.1016/S0021-9673(99)00595-6

    Article  CAS  PubMed  Google Scholar 

  • Cederbaum AI, Lu Y, Wu D (2009) Role of oxidative stress in alcohol-induced liver injury. Arch Toxicol 83:519–548. doi:10.1007/s00204-009-0432-0

    Article  CAS  PubMed  Google Scholar 

  • Cenesiz S, Yarim GF, Karabulut AB, Ara C (2007) Changing of antioxidant enzyme activity on the biliary obstructed rats treated with resveratrol. Dtsch Tierarztl Wochenschr 114:345–348

    CAS  PubMed  Google Scholar 

  • Chan CC, Cheng LY, Lin CL, Huang YH, Lin HC, Lee FY (2011) The protective role of natural phytoalexin resveratrol on inflammation, fibrosis and regeneration in cholestatic liver injury. Mol Nutr Food Res 55:1841–1849. doi:10.1002/mnfr.201100374

    Article  CAS  PubMed  Google Scholar 

  • Chan CC, Lee KC, Huang YH, Chou CK, Lin HC, Lee FY (2014) Regulation by resveratrol of the cellular factors mediating liver damage and regeneration after acute toxic liver injury. J Gastroenterol Hepatol 29:603–613. doi:10.1111/jgh.12366

    Article  CAS  PubMed  Google Scholar 

  • Chang CC, Chang CY, Huang JP, Hung LM (2012) Effect of resveratrol on oxidative and inflammatory stress in liver and spleen of streptozotocin-induced type 1 diabetic rats. Chin J Physiol 55:192–201. doi:10.4077/CJP.2011.BAA012

    Article  CAS  PubMed  Google Scholar 

  • Chávez E, Reyes-Gordillo K, Segovia J, Shibayama M, Tsutsumi V, Vergara P, Moreno MG, Muriel P (2008) Resveratrol prevents fibrosis, NF-kappaB activation and TGF-beta increases induced by chronic CCl4 treatment in rats. J Appl Toxicol 28:35–43. doi:10.1002/jat.1249

    Article  PubMed  CAS  Google Scholar 

  • Colell A, Garcia-Ruiz C, Miranda M, Ardite E, Marì M, Morales A, Corrales F, Kaplowitz N, Fernandez-Checa JC (1998) Selective glutathione depletion of mitochondria by ethanol sensitizes hepatocytes to tumor necrosis factor. Gastroenterology 115:1541–1551. doi:10.1016/S0016-5085(98)70034-4

    Article  CAS  PubMed  Google Scholar 

  • Conte E, Fagone E, Fruciano M, Gili E, Iemmolo M, Vancheri C (2014) Anti-inflammatory and antifibrotic effects of resveratrol in the lung. Histol Histopathol 30(5):523–529. doi:10.14670/HH-30.523

    PubMed  Google Scholar 

  • Cottart CH, Nivet-Antoine V, Laguillier-Morizot C, Beaudeux JL (2010) Resveratrol bioavailability and toxicity in humans. Mol Nutr Food Res 54:7–16. doi:10.1002/mnfr.200900437

    Article  CAS  PubMed  Google Scholar 

  • Crabb DW, Liangpunsakul S (2006) Alcohol and lipid metabolism. J Gastroenterol Hepatol 21:56–60. doi:10.1111/j.1440-1746.2006.04582.x

    Article  CAS  Google Scholar 

  • Cunningham CC, Bailey SM (2001) Ethanol consumption and liver mitochondria function. Biol Signals Recept 10(3–4):271–282. doi:10.1159/000046892

    Article  CAS  PubMed  Google Scholar 

  • Curzio M, Esterbauer H, Di Mauro C, Cecchini G, Dianzani MU (1986) Chemotactic activity of the lipid peroxidation product 4-hydroxynonenal and homologous hydroxyalkenals. Biol Chem Hoppe Seyler 367:321–329

    Article  CAS  PubMed  Google Scholar 

  • Dani C, Oliboni LS, Pasquali MA, Oliveira MR, Umezu FM, Salvador M, Moreira JC, Henriques JÁ (2008) Intake of purple juice as a hepatoprotective agent in Wistar rats. J Med Food 11:127–132. doi:10.1089/jmf.2007.558

    Article  CAS  PubMed  Google Scholar 

  • Di Pascoli M, Diví M, Rodríguez-Vilarrupla A, Rosado E, Gracia-Sancho J, Vilaseca M, Bosch J, García-Pagán JC (2013) Resveratrol improves intrahepatic endothelial dysfunction and reduces hepatic fibrosis and portal pressure in cirrhotic rats. J Hepatol 58:904–910. doi:10.1016/j.jhep.2012.12.012

    Article  PubMed  CAS  Google Scholar 

  • Fernandez-Checa JC, Hirano T, Tsukamoto H, Kaplowitz N (1993) Mitochondrial glutathione depletion in alcoholic liver disease. Alcohol 10(6):469–475. doi:10.1016/0741-8329(93)90067-X

    Article  CAS  PubMed  Google Scholar 

  • Fernandez-Checa JC, Kaplowitz N, García-Ruiz C, Colell A, Miranda M, Marí M, Ardite E, Morales A (1997) GSH transport in mitochondria: defense against TNF-induced oxidative stress and alcohol-induced defect. Am J Physiol 273:7–17

    Google Scholar 

  • Fernandez-Checa JC, Garcia-Ruiz C, Colell A, Morales A, Mari M, Miranda M, Ardite E (1998) Oxidative stress: role of mitochondria and protection by glutathione. BioFactors 8(1–2):7–11

    Article  CAS  PubMed  Google Scholar 

  • French SW (2004) The role of hypoxia in the pathogenesis of alcoholic liver disease. Hepatol Res 29:69–74. doi:10.1016/j.hepres.2004.02.006

    Article  CAS  PubMed  Google Scholar 

  • Galli A, Pinaire J, Fischer M, Dorris R, Crabb DW (2001) The transcriptional and DNA binding activity of peroxisome proliferator-activated receptor alpha is inhibited by ethanol metabolism. A novel mechanism for the development of ethanol-induced fatty liver. J Biol Chem 276:68–75. doi:10.1074/jbc.M008791200

    Article  CAS  PubMed  Google Scholar 

  • Gedik E, Girgin S, Ozturk H, Obay BD, Ozturk H, Buyukbayram H (2008) Resveratrol attenuates oxidative stress and histological alternations induced by liver ischemia/reperfusion in rats. World J Gastroenterol 14:7101–7106. doi:10.3748/wjg.14.7101

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Godichaud S, Krisa S, Couronné B, Dubuisson L, Mérillon JM, Desmoulière A, Rosenbaum J (2000) Deactivation of cultured human liver myofibroblasts by trans-resveratrol, a grapevine-derived polyphenol. Hepatology 31:922–931. doi:10.1053/he.2000.5848

    Article  CAS  PubMed  Google Scholar 

  • Granzotto A, Zatta P (2014) Resveratrol and Alzheimer’s disease: message in a bottle on red wine and cognition. Front Aging Neurosci 6:95. doi:10.3389/fnagi.2014.00095

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Grattagliano I, Vendemiale G, Sabbà G, Buonamico P, Altomare E (1996) Oxidation of circulating proteins in alcoholics: role of acetaldehyde and xanthine oxidase. J Hepatol 25:28–36. doi:10.1016/S0168-8278(96)80324-2

    Article  CAS  PubMed  Google Scholar 

  • Gülçin I (2010) Antioxidant properties of resveratrol: a structure–activity insight. Innov Food Sci Emerg 11:210–218. doi:10.1016/j.ifset.2009.07.002

    Article  CAS  Google Scholar 

  • Hassan-Khabbar S, Cottart C, Wendum D, Vibert F, Clot JP, Savouret JF, Conti M, Nivet-Antoine V (2008) Postischemic treatment by trans-resveratrol in rat liver ischemia-reperfusion: a possible strategy in liver surgery. Liver Transpl 14:451–459. doi:10.1002/lt.21405

    Article  PubMed  Google Scholar 

  • Hassan-Khabbar S, Vamy M, Cottart CH, Wendum D, Vibert F, Savouret JF, Thérond P, Clot JP, Waligora AJ, Nivet-Antoine V (2010) Protective effect of post-ischemic treatment with trans-resveratrol on cytokine production and neutrophil recruitment by rat liver. Biochimie 92:405–410. doi:10.1016/j.biochi.2009.12.009

    Article  CAS  PubMed  Google Scholar 

  • Hodge AM, English DR, O’Dea K, Giles GG (2006) Alcohol intake, consumption pattern and beverage type, and the risk of Type II diabetes. Diabet Med 23:690–697. doi:10.1111/j.1464-5491.2006.01864.x

    Article  CAS  PubMed  Google Scholar 

  • Holford NHG (1987) Clinical pharmacokinetics of ethanol. Clin Pharmacokinet 13:273–292. doi:10.2165/00003088-198713050-00001

    Article  CAS  PubMed  Google Scholar 

  • Holthoff JH, Wang Z, Seely KA, Gokden N, Mayeux PR (2011) Resveratrol improves renal microcirculation, protects the tubular epithelium, and prolongs survival in a mouse model of sepsis-induced acute kidney injury. Kidney Int 81:370–378. doi:10.1038/ki.2011.347

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Houtkooper RH, Pirinen E, Auwerx J (2012) Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol 13:225–238. doi:10.1038/nrm3293

    Article  CAS  PubMed  Google Scholar 

  • Hsu SC, Huang SM, Chen A, Sun CY, Lin SH, Chen JS, Liu ST, Hsu YJ (2014) Resveratrol increases anti-aging Klotho gene expression via the activating transcription factor 3/c-Jun complex-mediated signaling pathway. Int J Biochem Cell Biol 53:361–371. doi:10.1016/j.biocel.2014.06.002

    Article  CAS  PubMed  Google Scholar 

  • Hultcrantz R, Bissell DM, Roll FJ (1991) Iron mediates production of a neutrophil chemoattractant by rat hepatocytes metabolizing ethanol. J Clin Invest 87:45–49. doi:10.1172/JCI114999

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ishak KG, Zimmerman HJ, Ray MB (1991) Alcoholic liver disease: pathologic, pathogenetic and clinical aspects. Alcohol Clin Exp Res 15:45–66. doi:10.1111/j.1530-0277.1991.tb00518.x

    Article  CAS  PubMed  Google Scholar 

  • Israel Y, Hurwitz E, Niemelä O, Arnon R (1986) Monoclonal and polyclonal antibodies against acetaldehyde-containing epitopes in acetaldehyde-protein adducts. Proc Natl Acad Sci USA 83:7923–7927

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jagavelu K, Routray C, Shergill U, O’Hara SP, Faubion W, Shah VH (2010) Endothelial cell toll-like receptor 4 regulates fibrosis-associated angiogenesis in the liver. Hepatology 52:590–601. doi:10.1002/hep.23739

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jamroz A, Beltowski J (2001) Antioxidant capacity of select wines. Med Sci Monit 7:1198–1202

    CAS  PubMed  Google Scholar 

  • Jannin B, Menzel M, Berlot JP, Delmas D, Lancon A, Latruffe N (2004) Transport of resveratrol, a cancer chemopreventive agent, to cellular targets: plasmatic protein binding and cell uptake. Biochem Pharmacol 68(6):1113–1118. doi:10.1016/j.bcp.2004.04.028

    Article  CAS  PubMed  Google Scholar 

  • Jeon BT, Jeong EA, Shin HJ, Lee Y, Lee DH, Kim HJ, Kang SS, Cho GJ, Choi WS, Roh GS (2012) Resveratrol attenuates obesity associated peripheral and central inflammation and improves memory deficit in mice fed a high-fat diet. Diabetes 61:1444–1454. doi:10.2337/db11-1498

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Juránek I, Nikitovic D, Kouretas D, Hayes AW, Tsatsakis AM (2013) Biological importance of reactive oxygen species in relation to difficulties of treating pathologies involving oxidative stress by exogenous antioxidants. Food Chem Toxicol 61:240–247. doi:10.1016/j.fct.2013.08.074

    Article  PubMed  CAS  Google Scholar 

  • Kasdallah-Grissa A, Mornagui B, Aouani E, Hammami M, Gharbi N, Kamoun A, El-Fazaa S (2006) Protective effect of resveratrol on ethanol-induced lipid peroxidation in rats. Alcohol Alcohol 41:236–239. doi:10.1093/alcalc/agh256

    Article  CAS  PubMed  Google Scholar 

  • Kasdallah-Grissa A, Mornagui B, Aouani E, Hammami M, El May M, Gharbi N, Kamoun A, El-Fazaâ S (2007) Resveratrol, a red wine polyphenol, attenuates ethanol-induced oxidative stress in rat liver. Life Sci 80:1033–1039. doi:10.1016/j.lfs.2006.11.044

    Article  CAS  PubMed  Google Scholar 

  • Kawada N, Seki S, Inoue M, Kuroki T (1998) Effect of antioxidants, resveratrol, quercetin, and N-acetylcysteine, on the functions of cultured rat hepatic stellate cells and Kupffer cells. Hepatology 27:1265–1274. doi:10.1002/hep.510270512

    Article  CAS  PubMed  Google Scholar 

  • Keegan A, Martini R, Batey R (1995) Ethanol-related liver injury in the rat: a model of steatosis, inflammation and pericentral fibrosis. J Hepatol 23(5):591–600. doi:10.1016/0168-8278(95)80067-0

    Article  CAS  PubMed  Google Scholar 

  • Kono H, Rusyn I, Uesugi T, Yamashina S, Connor HD, Dikalova A, Mason RP, Thurman RG (2001) Diphenyleneiodonium sulfate, an NADPH oxidase inhibitor, prevents early alcohol-induced liver injury in the rat. Am J Physiol Gastrointest Liver Physiol 280:1005–1012

    Google Scholar 

  • Kourkoutas Y, Kanellaki M, Koutinas AA, Tzia C (2006) Effect of storage of immobilized cells at ambient temperature on volatile by-products during wine-making. J Food Eng 74(2):217–223. doi:10.1016/j.jfoodeng.2005.03.013

    Article  CAS  Google Scholar 

  • Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127:1109–1122. doi:10.1016/j.cell.2006.11.013

    Article  CAS  PubMed  Google Scholar 

  • Landrault N, Larronde F, Delaunay JC, Castagnino C, Vercauteren J, Merillon JM, Gasc F, Cros G, Teissedre PL (2002) Levels of stilbene oligomers and astilbin in French wines and grapes during noble rot development. J Agric Food Chem 50:2046–2052. doi:10.1021/jf010794g

    Article  CAS  PubMed  Google Scholar 

  • Lands WE (1995) Cellular signals in alcohol-induced liver injury: a review. Alcohol Clin Exp Res 19:928–938. doi:10.1111/j.1530-0277.1995.tb00969.x

    Article  CAS  PubMed  Google Scholar 

  • Lea AG, Piggott JR, Piggott JR (2003) Fermented beverage production. Springer, United States

    Book  Google Scholar 

  • Lee ES, Shin MO, Yoon S, Moon JO (2010) Resveratrol inhibits dimethylnitrosamine-induced hepatic fibrosis in rats. Arch Pharm Res 33:925–932. doi:10.1007/s12272-010-0616-4

    Article  CAS  PubMed  Google Scholar 

  • Li L, Hai J, Li Z, Zhang Y, Peng H, Li K, Weng X (2014) Resveratrol modulates autophagy and NF-κB activity in a murine model for treating non-alcoholic fatty liver disease. Food Chem Toxicol 63:166–173. doi:10.1016/j.fct.2013.08.036

    Article  CAS  PubMed  Google Scholar 

  • Lieber CS (1994) Alcohol and the liver: 1994 update. Gastroenterology 106(4):1085–1105

    CAS  PubMed  Google Scholar 

  • Lieber CS (1997) Ethanol metabolism, cirrhosis and alcoholism. Clin Chim Acta 257:59–84. doi:10.1016/S0009-8981(96)06434-0

    Article  CAS  PubMed  Google Scholar 

  • Lieber CS (1999) Microsomal ethanol-oxidizing system (MEOS): the first 30 years (1968–1998)—a review. Alcohol Clin Exp Res 23:991–1007. doi:10.1111/j.1530-0277.1999.tb04217.x

    CAS  PubMed  Google Scholar 

  • Lieber CS, Leo MA, Wang X, Decarli LM (2008) Effect of chronic alcohol consumption on Hepatic SIRT1 and PGC-1alpha in rats. Biochem Biophys Res Commun 370:44–48. doi:10.1016/j.bbrc.2008.03.005

    Article  CAS  PubMed  Google Scholar 

  • Liu L, Fan Z, Tang Y, Ke Z (2014) The resveratrol attenuates ethanol-induced hepatocyte apoptosis via inhibiting ER-related caspase-12 activation and PDE activity. Alcohol Clin Exp Res 38(3):683–693. doi:10.1111/acer.12311

    Article  CAS  PubMed  Google Scholar 

  • López-Vélez M, Martínez-Martínez F, Del Valle-Ribes C (2003) The study of phenolic compounds as natural antioxidants in wine. Crit Rev Food Sci Nutr 43:233–244. doi:10.1080/10408690390826509

    Article  PubMed  Google Scholar 

  • Lu Y, Zhuge J, Wang X, Bai J, Cederbaum AI (2008) Cytochrome P450 2E1 contributes to ethanol-induced fatty liver in mice. Hepatology 47:1483–1494. doi:10.1002/hep.22222

    Article  CAS  PubMed  Google Scholar 

  • Maddrey WC (2000) Alcoholic-induced liver disease. Clin Liver Dis 4(1):115–131

    Article  CAS  PubMed  Google Scholar 

  • Madesh M, Hajnoczky G (2001) VDAC-dependent permeabilization of the outer mitochondrial membrane by superoxide induces rapid and massive cytochrome c release. J Cell Biol 155:1003–1015. doi:10.1083/jcb.200105057

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Malhi H, Gores GJ (2008) Cellular and molecular mechanisms of liver injury. Gastroenterology 134:1641–1654. doi:10.1053/j.gastro.2008.03.002

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Marier JF, Vachon P, Gritsas A, Zhang J, Moreau JP, Ducharme MP (2002) Metabolism and disposition of resveratrol in rats: extent of absorption, glucuronidation, and enterohepatic recirculation evidenced by a linked–rat model. J Pharmacol Exp Ther 302(1):369–373. doi:10.1124/jpet.102.033340

    Article  CAS  PubMed  Google Scholar 

  • McVicker BL, Tuma PL, Kharbanda KK, Lee SM, Tuma DJ (2009) Relationship between oxidative stress and hepatic glutathione levels in ethanol–mediated apoptosis of polarized hepatic cells. World J Gastroenterol 15:2609–2616. doi:10.3748/wjg.15.2609

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mello T, Ceni E, Surrenti C, Galli A (2008) Alcohol induced hepatic fibrosis: role of acetaldehyde. Mol Aspects Med 29:17–21. doi:10.1016/j.mam.2007.10.001

    Article  CAS  PubMed  Google Scholar 

  • Mira L, Maia L, Barreira L, Manso CF (1995) Evidence for free radical generation due to NADH oxidation by aldehyde oxidase during ethanol metabolism. Arch Biochem Biophys 318:53–58. doi:10.1006/abbi.1995.1203

    Article  CAS  PubMed  Google Scholar 

  • Muñoz-González I, Espinosa-Martos I, Rodríguez JM, Jiménez-Girón A, Martín-Álvarez PJ, Bartolomé B, Moreno-Arribas MV (2014) Moderate consumption of red wine can modulate human intestinal inflammatory response. J Agric Food Chem 62:10567–10575. doi:10.1021/jf503310c

    Article  PubMed  CAS  Google Scholar 

  • Nanji AA, Hiller-Sturmhofel S (1997) Apoptosis and necrosis: two types of cell death in liver disease. Alcohol Health Res World 21(4):325–330

    CAS  PubMed  Google Scholar 

  • Natori S, Rust C, Stadheim LM, Srinivasan A, Burgart LJ, Gores GJ (2001) Hepatocyte apoptosis is a pathological feature of human alcoholic hepatitis. J Hepatol 34:248–253. doi:10.1016/S0168-8278(00)00089-1

    Article  CAS  PubMed  Google Scholar 

  • Norberg A, Jones AW, Hahn RG, Gabrielsson JL (2003) Role of variability in explaining ethanol pharmacokinetics: research and forensic applications. Clin Pharmacokinet 42:1–31. doi:10.2165/00003088-200342010-00001

    Article  CAS  PubMed  Google Scholar 

  • Okay E, Simsek T, Subasi C, Gunes A, Duruksu G, Gurbuz Y, Gacar G, Karaoz E (2014) Cross effects of resveratrol and mesenchymal stem cells on liver regeneration and homing in partially hepatectomized rats. Stem Cell Rev Rep. doi:10.1007/s12015-014-9572-6

    Google Scholar 

  • Oshino N, Oshino R, Chance B (1973) The characteristics of the peroxidatic reaction in ethanol oxidation. Biochem J 131:555–567

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Paik YH, Schwabe RF, Bataller R, Russo MP, Jobin C, Brenner DA (2003) Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells. Hepatology 37:1043–1055. doi:10.1053/jhep.2003.50182

    Article  CAS  PubMed  Google Scholar 

  • Peng Z, Borea PA, Varani K, Wilder T, Yee H, Chiriboga L, Blackburn MR, Azzena G, Resta G, Cronstein BN (2009) Adenosine signaling contributes to ethanol-induced fatty liver in mice. J Clin Invest 119:582–594. doi:10.1172/JCI37409

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pessayre D, Fromenty B (2005) NASH a mitochondrial disease. J Hepatol 42:928–940. doi:10.1016/j.jhep.2005.03.004

    Article  CAS  PubMed  Google Scholar 

  • Poulsen MM, Vestergaard PF, Clasen BF, Radko Y, Christensen LP, Stødkilde-Jørgensen H, Møller N, Jessen N, Pedersen SB, Jørgensen JO (2013) High-Dose resveratrol supplementation in obese men: an investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition. Diabetes 4:1186–1195. doi:10.2337/db12-0975

    Article  CAS  Google Scholar 

  • Rao DNR, Yang MX, Lasker JM, Cederbaum AI (1996) 1-hydroxyethyl radical formation during NADPH- and NADH-dependent oxidation of ethanol by human liver microsomes. Mol Pharmacol 49:814–821

    CAS  PubMed  Google Scholar 

  • Reinke LA, Moore DR, McCay PB (1997) Mechanisms for metabolism of ethanol to 1-hydroxyethyl radicals in rat liver microsomes. Arch Biochem Biophys 348:9–14. doi:10.1006/abbi.1997.0387

    Article  CAS  PubMed  Google Scholar 

  • Renaud S, de Lorgeril M (1992) Wine, alcohol, platelets, and the French Paradox for coronary heart disease. Lancet 339:1523–1526. doi:10.1016/0140-6736(92)91277-F

    Article  CAS  PubMed  Google Scholar 

  • Rivera H, Shibayama M, Tsutsumi V, Perez-Alvarez V, Muriel P (2008) Resveratrol and trimethylated resveratrol protect from acute liver damage induced by CCl4 in the rat. J Appl Toxicol 28:147–155. doi:10.1002/jat.1260

    Article  CAS  PubMed  Google Scholar 

  • Romero-Pérez A, Lamuela-Raventós RM, Waterhouse AL, de la Torre-Boronat MC (1996) Levels of cis–and trans–resveratrol and their glucosides in white and rosé Vitis vinifera wines from Spain. J Agric Food Chem 44:2124–2128

    Article  Google Scholar 

  • Ronis MJJ, Lindros KO, Ingelman-Sundberg M (1996) The CYP2E family. In: Ioannides C (ed) Cytochromes P450: metabolic and toxicological aspects. CRC Press, Boca Raton, pp 211–239

    Google Scholar 

  • Sahpazidou D, Geromichalos GD, Stagos D, Apostolou A, Haroutounian SA, Tsatsakis AM, Tzanakakis GN, Hayes AW, Kouretas D (2014) Anticarcinogenic activity of polyphenolic extracts from grape stems against breast, colon, renal and thyroid cancer cells. Toxicol Lett 230(2):218–224. doi:10.1016/j.toxlet.2014.01.042

    Article  CAS  PubMed  Google Scholar 

  • Saldanha JF, Leal Vde O, Stenvinkel P, Carraro-Eduardo JC, Mafra D (2013) Resveratrol: why is it a promising therapy for chronic kidney disease patients? Oxid Med Cell Longev Article ID 963217. http://dx.doi.org/10.1155/2013/963217

  • Sato M, Suzuki S, Senoo H (2003) Hepatic stellate cells: unique characteristics in cell biology and phenotype. Cell Struct Funct 28:105–112. doi:10.1247/csf.28.105

    Article  CAS  PubMed  Google Scholar 

  • Seki E, De Minicis S, Osterreicher CH, Kluwe J, Osawa Y, Brenner DA, Schwabe RF (2007) TLR4 enhances TGF-beta signaling and hepatic fibrosis. Nat Med 13:1324–1332. doi:10.1038/nm1663

    Article  CAS  PubMed  Google Scholar 

  • Senoo H (2004) Structure and function of hepatic stellate cells. Med Electron Microsc 37:3–15. doi:10.1007/s00795-003-0230-3

    Article  CAS  PubMed  Google Scholar 

  • Shattemberg JM, Wang Y, Singh R, Rigoli RM, Czaja MJ (2005) Hepatocyte CYP2E1 overexpression and steatohepatitis lead to impaired hepatic insulin signalling. J Biol Chem 280:9887–9894. doi:10.1074/jbc.M410310200

    Article  CAS  Google Scholar 

  • Shaw S, Jayatilleke E (1990a) Ethanol-induced iron mobilization: role of acetaldehyde-aldehyde oxidase generated superoxide. Free Radic Biol Med 9:11–15

    Article  CAS  PubMed  Google Scholar 

  • Shaw S, Jayatilleke E (1990b) The role of aldehyde oxidase in ethanol-induced hepatic lipid peroxidation in the rat. Biochem J268:579–583

    Article  Google Scholar 

  • Slater TF (1988) Free radicals mechanisms in tissue injury with special reference to the cytotoxic effects of ethanol and related alcohols. In: Nordmann R, Ribiere C, Rouach H (eds) Alcohol toxicity and free radical mechanisms, advances in biosciences, vol 71. Pergamon Press, Oxford, pp 1–9

    Google Scholar 

  • Soleas GJ, Goldberg DM, Karumanchiri A, Diamandis EP, Ng E (1995) Influences of viticultural and enological factors on changes in cis– and trans–resveratrol in commercial wines. J Wine Res 6:107–121. doi:10.1080/09571269508718028

    Article  Google Scholar 

  • Souza IC, Martins LA, Coelho BP, Grivicich I, Guaragna RM, Gottfried C, Borojevic R, Guma FC (2008) Resveratrol inhibits cell growth by inducing cell cycle arrest in activated hepatic stellate cells. Mol Cell Biochem 315:1–7. doi:10.1007/s11010-008-9781-x

    Article  CAS  PubMed  Google Scholar 

  • Stewart S, Jones D, Day CP (2001) Alcoholic liver disease: new insights into mechanisms and preventative strategies. Trends Mol Med 7:408–413. doi:10.1016/S1471-4914(01)02096-2

    Article  CAS  PubMed  Google Scholar 

  • Su GL, Klein RD, Aminlari A, Zhang HY, Steinstraesser L, Alarcon WH, Remick DG, Wang SC (2000) Kupffer cell activation by lipopolysaccharide in rats: role for lipopolysaccharide binding protein and toll-like receptor 4. Hepatology 31:932–936. doi:10.1053/he.2000.5634

    Article  CAS  PubMed  Google Scholar 

  • Szabo G, Bala S (2010) Alcoholic liver disease and the gut-liver axis. World J Gastroenterol 16:1321–1329

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Szkudelski T, Szkudelska K (2011) Anti-diabetic effects of resveratrol. Ann N Y Acad Sci 1215:34–39. doi:10.1111/j.1749-6632.2010.05844.x

    Article  CAS  PubMed  Google Scholar 

  • Tamai H, Kato S, Horie Y, Ohki E, Yokoyama H, Ishii H (2000) Effect of acute ethanol administration on the intestinal absorption of endotoxin in rats. Alcohol Clin Exp Res 24:390–394. doi:10.1111/j.1530-0277.2000.tb04629.x

    Article  CAS  PubMed  Google Scholar 

  • Toth P, Tarantini S, Springo Z, Tucsek Z, Gautam T, Giles CB, Wren JD, Koller A, Sonntag WE, Csiszar A, Ungvari Z (2015) Aging exacerbates hypertension-induced cerebral microhemorrhages in mice: role of resveratrol treatment in vasoprotection. Aging Cell. doi:10.1111/acel.12315

    PubMed Central  Google Scholar 

  • Vina J, Estrela JM, Guerri C, Romero FJ (1980) Effect of ethanol on glutathione concentration in isolated hepatocytes. Biochem J 188(2):549–552

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Walle T (2011) Bioavailability of resveratrol. Ann N Y Acad Sci 1215:9–15. doi:10.1111/j.1749-6632.2010.05842.x

    Article  CAS  PubMed  Google Scholar 

  • Walle T, Hsieh F, DeLegge MH, Oatis JE Jr, Walle UK (2004) High absorption but very low bioavailability of oral resveratrol metabolism in humans. Drug Metab Dispos 32:1377–1382. doi:10.1124/dmd.104.000885

    Article  CAS  PubMed  Google Scholar 

  • Wang K (2014) Molecular mechanisms of hepatic apoptosis. Cell Death Dis 5:e996. doi:10.1038/cddis.2013.499

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wheeler GL, Trotter EW, Dawes IW, Grant CM (2003) Coupling of the transcriptional regulation of glutathione biosynthesis to the availability of glutathione and methionine via the Met4 and Yap1 transcription factors. J Biol Chem 278(50):49920–49928. doi:10.1074/jbc.M310156200

    Article  CAS  PubMed  Google Scholar 

  • Yang H, Lee MK, Kim YC (2005a) Protective activities of stilbene glycosides from Acer mono leaves against H2O2-induced oxidative damage in primary cultured rat hepatocytes. J Agric Food Chem 53:4182–4186. doi:10.1021/jf050093+

    Article  CAS  PubMed  Google Scholar 

  • Yang H, Sung SH, Kim YC (2005b) Two new hepatoprotective stilbene glycosides from Acer mono leaves. J Nat Prod 68:101–103. doi:10.1021/np0497907

    Article  CAS  PubMed  Google Scholar 

  • Yoshino J, Conte C, Fontana L, Mittendorfer Imai S, Schechtman KB, Gu C, Kunz I, Rossi Fanelli F, Patterson BW, Klein S (2012) Resveratrol supplementation does not improve metabolic function in non-obese women with normal glucose tolerance. Cell Metab 16:658–664. doi:10.1016/j.cmet.2012.09.015

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • You M, Fischer M, Deeg MA, Crabb DW (2002) Ethanol induces fatty acid synthesis pathways by activation of sterol regulatory element binding protein (SREBP). J Biol Chem 277:29342–29347

    Article  CAS  PubMed  Google Scholar 

  • You M, Matsumoto M, Pacold CM, Cho WK, Crabb DW (2004) The role of AMP-activated protein kinase in the action of ethanol in the liver. Gastroenterology 127:1798–1808. doi:10.1053/j.gastro.2004.09.049

    Article  CAS  PubMed  Google Scholar 

  • You M, Considine RV, Leone TC, Kelly DP, Crabb DW (2005) Role of adiponectin in the protective action of dietary saturated fat against alcoholic fatty liver in mice. Hepatology 42:568–577. doi:10.1002/hep.20821

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • You M, Liang X, Ajmo JM, Ness GC (2008) Involvement of mammalian sirtuin 1 in the action of ethanol in the liver. Am J Physiol Gastrointest Liver Physiol 294:892–898. doi:10.1152/ajpgi.00575.2007

    Article  CAS  Google Scholar 

  • Yu W, Fu YC, Wang W (2012) Cellular and molecular effects of resveratrol in health and disease. J Cell Biochem 113:752–759. doi:10.1002/jcb.23431

    Article  CAS  PubMed  Google Scholar 

  • Zhao K, Zhao GM, Wu D, Soong Y, Birk AV, Schiller PW, Szeto HH (2004) Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. J Biol Chem 279:34682–34690. doi:10.1074/jbc.M402999200

    Article  CAS  PubMed  Google Scholar 

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  1. UCIBIO-REQUIMTE, Laboratory of Histology and Embryology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira no. 228, 4050-313, Porto, Portugal

    Paula Silva

  2. UCIBIO-REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal

    Eduarda Fernandes

  3. UCIBIO-REQUIMTE, Department of Biological Sciences, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira no. 228, 4050-313, Porto, Portugal

    Félix Carvalho

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Silva, P., Fernandes, E. & Carvalho, F. Dual effect of red wine on liver redox status: a concise and mechanistic review. Arch Toxicol 89, 1681–1693 (2015). https://doi.org/10.1007/s00204-015-1538-1

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