Role of oxidative stress in the pathogenesis of alcohol-induced liver disease

References

• Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74–108.
   PubMed Web of Science ®Google Scholar
• El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007;132:2557–2576.
   PubMed Web of Science ®Google Scholar
• Venook AP, Papandreou C, Furuse J, de Guevara LL. The incidence and epidemiology of hepatocellular carcinoma: a global and regional perspective. Oncologist 2010;15:5–13.
   PubMed Web of Science ®Google Scholar
• Day CP. Genes or environment to determine alcoholic liver disease and non-alcoholic fatty liver disease. Liver Int 2006;26:1021–1028.
   PubMed Web of Science ®Google Scholar
• Dey A, Cederbaum AI. Alcohol and oxidative liver injury. Hepatology 2006;43:S63–S74.
   PubMed Web of Science ®Google Scholar
• Albano E. New concepts in the pathogenesis of alcoholic liver disease. Expert Rev Gastroenterol Hepatol 2008;2: 749–759.
   PubMedGoogle Scholar
• Cohen JI, Chen X, Nagy LE. Redox signaling and the innate immune system in alcoholic liver disease. Antioxid Redox Signal 2011;15:523–534.
   PubMed Web of Science ®Google Scholar
• Chance B, Sies H, Boveris A. Hydroperoxide metabolism in mammalian organs. Physiol Rev 1979;59:527–605.
   PubMed Web of Science ®Google Scholar
• Blanck J, Ristau O, Zhukov AA, Archakov AI, Rein H, Ruckpaul K. Cytochrome P-450 spin state and leakiness of the monooxygenase pathway. Xenobiotica 1991;21: 121–135.
   PubMed Web of Science ®Google Scholar
• Hebbel RP, Morgan WT, Eaton JW, Hedlund BE. Accelerated autoxidation and heme loss due to instability of sickle hemoglobin. Proc Natl Acad Sci USA 1988;85:237–241.
   PubMed Web of Science ®Google Scholar
• Ksenzenko M, Konstantinov AA, Khomutov GB, Tikhonov AN, Ruuge EK. Effect of electron transfer inhibitors on superoxide generation in the cytochrome bc1 site of the mitochondrial respiratory chain. FEBS Lett 1983;155:19–24.
   PubMed Web of Science ®Google Scholar
• de Groot H. Reactive oxygen species in tissue injury. Hepatogastroenterology 1994;41:328–332.
   PubMed Web of Science ®Google Scholar
• Perry G, Raina AK, Nunomura A, Wataya T, Sayre LM, Smith MA. How important is oxidative damage? Lessons from Alzheimer's disease. Free Radic Biol Med 2000;28:831–834.
   PubMed Web of Science ®Google Scholar
• Nakazawa H, Genka C, Fujishima M. Pathological aspects of active oxygens/free radicals. Jpn J Physiol 1996;46: 15–32.
   PubMedGoogle Scholar
• Tien Kuo M, Savaraj N. Roles of reactive oxygen species in hepatocarcinogenesis and drug resistance gene expression in liver cancers. Mol Carcinog 2006;45:701–709.
   PubMed Web of Science ®Google Scholar
• Ha HL, Shin HJ, Feitelson MA, Yu DY. Oxidative stress and antioxidants in hepatic pathogenesis. World J Gastroenterol 2010;16:6035–6043.
   PubMed Web of Science ®Google Scholar
• Vaziri ND. Roles of oxidative stress and antioxidant therapy in chronic kidney disease and hypertension. Curr Opin Nephrol Hypertens 2004;13:93–99.
   PubMedGoogle Scholar
• Ichikawa I, Kiyama S, Yoshioka T. Renal antioxidant enzymes: their regulation and function. Kidney Int 1994;45:1–9.
   PubMed Web of Science ®Google Scholar
• Rhee SG, Chae HZ, Kim K. Peroxiredoxins: a historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling. Free Radic Biol Med 2005;38:1543–1552.
   PubMed Web of Science ®Google Scholar
• Lillig CH, Berndt C, Holmgren A. Glutaredoxin systems. Biochim Biophys Acta 2008;1780:1304–1317.
   PubMed Web of Science ®Google Scholar
• Yu BP. Cellular defenses against damage from reactive oxygen species. Physiol Rev 1994;74:139–162.
   PubMed Web of Science ®Google Scholar
• Halliwell B. Antioxidant defence mechanisms: from the beginning to the end (of the beginning). Free Radic Res 1999;31:261–272.
   PubMed Web of Science ®Google Scholar
• Hill DB, Kugelmas M. Alcoholic liver disease. Treatment strategies for the potentially reversible stages. Postgrad Med 1998;103:261–264, 267–268, 273–275.
   Web of Science ®Google Scholar
• Siegmund SV, Brenner DA. Molecular pathogenesis of alcohol-induced hepatic fibrosis. Alcohol Clin Exp Res 2005; 29:102S–109S.
   Google Scholar
• Lalor PF, Faint J, Aarbodem Y, Hubscher SG, Adams DH. The role of cytokines and chemokines in the development of steatohepatitis. Semin Liver Dis 2007;27:173–193.
   PubMed Web of Science ®Google Scholar
• Koteish A, Yang S, Lin H, Huang X, Diehl AM. Chronic ethanol exposure potentiates lipopolysaccharide liver injury despite inhibiting Jun N-terminal kinase and caspase 3 activation. J Biol Chem 2002;277:13037–13044.
   PubMed Web of Science ®Google Scholar
• Schäfer C, Parlesak A, Schütt C, Bode JC, Bode C. Concentrations of lipopolysaccharide-binding protein, bactericidal/permeability-increasing protein, soluble CD14 and plasma lipids in relation to endotoxaemia in patients with alcoholic liver disease. Alcohol Alcohol 2002;37:81–86.
   PubMed Web of Science ®Google Scholar
• Crosse KI, Anania FA. Alcoholic Hepatitis. Curr Treat Options Gastroenterol. 2002;5:417–423.
   Google Scholar
• Zakhari S, Li TK. Determinants of alcohol use and abuse: impact of quantity and frequency patterns on liver disease. Hepatology 2007;46:2032–2039.
   PubMed Web of Science ®Google Scholar
• Mathurin P, Deltenre P. Effect of binge drinking on the liver: an alarming public health issue?Gut 2009;58:613–617.
   PubMed Web of Science ®Google Scholar
• Aroor AR, Roy LJ, Restrepo RJ, Mooney BP, Shukla SD. A proteomic analysis of liver after ethanol binge in chronically ethanol treated rats. Proteome Sci 2012;10:29.
   Google Scholar
• Hirano T. Alcohol consumption and oxidative DNA damage. Int J Environ Res Public Health 2011;8:2895–2906.
   PubMedGoogle Scholar
• Nordmann R, Ribière C, Rouach H. Implication of free radical mechanisms in ethanol-induced cellular injury. Free Radic Biol Med 1992;12:219–240.
   PubMed Web of Science ®Google Scholar
• Cederbaum AI. Microsomal generation of reactive oxygen species and their possible role in alcohol hepatotoxicity. Alcohol Alcohol Suppl 1991;1:291–296.
   PubMedGoogle Scholar
• Oh SI, Kim CI, Chun HJ, Park SC. Chronic ethanol consumption affects glutathione status in rat liver. J Nutr 1998; 128:758–763.
   PubMed Web of Science ®Google Scholar
• Devi BG, Henderson GI, Frosto TA, Schenker S. Effect of ethanol on rat fetal hepatocytes: studies on cell replication, lipid peroxidation and glutathione. Hepatology 1993;18:648–659.
   PubMed Web of Science ®Google Scholar
• Husain K, Scott BR, Reddy SK, Somani SM. Chronic ethanol and nicotine interaction on rat tissue antioxidant defense system. Alcohol 2001;25:89–97.
   PubMed Web of Science ®Google Scholar
• Di Luzio NR. A mechanism of the acute ethanol-induced fatty liver and the modification of liver injury by antioxidants. Am J Pharm Sci Support Public Health 1966;15:50–63.
   Google Scholar
• Kamimura S, Gaal K, Britton RS, Bacon BR, Triadafilopoulos G, Tsukamoto H. Increased 4-hydroxynonenal levels in experimental alcoholic liver disease: association of lipid peroxidation with liver fibrogenesis. Hepatology 1992;16:448–453.
   PubMed Web of Science ®Google Scholar
• Niemelä O, Parkkila S, Ylä-Herttuala S, Halsted C, Witztum JL, Lanca A, Israel Y. Covalent protein adducts in the liver as a result of ethanol metabolism and lipid peroxidation. Lab Invest 1994;70:537–546.
   PubMed Web of Science ®Google Scholar
• Smathers RL, Galligan JJ, Stewart BJ, Petersen DR. Overview of lipid peroxidation products and hepatic protein modification in alcoholic liver disease. Chem Biol Interact 2011;192:107–112.
   PubMed Web of Science ®Google Scholar
• Sharma P, Jha AB, Dubey RS, Pessarakli M. Reactive oxygen species, oxidative damage, and antioxidative defense mechanism in plants under stressful conditions. J Bot 2012; Article ID 217037:26. doi:10.1155/2012/217037
   Google Scholar
• Bailey SM, Patel VB, Young TA, Asayama K, Cunningham CC. Chronic ethanol consumption alters the glutathione/glutathione peroxidase-1 system and protein oxidation status in rat liver. Alcohol Clin Exp Res 2001;25:726–733.
   PubMed Web of Science ®Google Scholar
• Kasai H, Nishimura S. Hydroxylation of deoxyguanosine at the C-8 position by ascorbic acid and other reducing agents. Nucleic Acids Res 1984;12:2137–2145.
   PubMed Web of Science ®Google Scholar
• Ajakaiye M, Jacob A, Wu R, Nicastro JM, Coppa GF, Wang P. Alcohol and hepatocyte-Kupffer cell interaction. Mol Med Rep 2011;4:597–602.
   Google Scholar
• Beier JI, McClain CJ. Mechanisms and cell signaling in alcoholic liver disease. Biol Chem 2010;391:1249–1264.
   PubMed Web of Science ®Google Scholar
• Zhu H, Jia Z, Misra H, Li YR. Oxidative stress and redox signaling mechanisms of alcoholic liver disease: updated experimental and clinical evidence. J Dig Dis 2012;13: 133–142.
   PubMed Web of Science ®Google Scholar
• McKillop IH, Schrum LW. Alcohol and liver cancer. Alcohol 2005;35:195–203.
   PubMed Web of Science ®Google Scholar
• Cunningham CC, Bailey SM. Ethanol consumption and liver mitochondria function. Biol Signals Recept 2001;10: 271–282.
   PubMedGoogle Scholar
• Boveris A, Fraga CG, Varsavsky AI, Koch OR. Increased chemiluminescence and superoxide production in the liver of chronically ethanol-treated rats. Arch Biochem Biophys 1983;227:534–541.
   PubMed Web of Science ®Google Scholar
• Kukiełka E, Dicker E, Cederbaum AI. Increased production of reactive oxygen species by rat liver mitochondria after chronic ethanol treatment. Arch Biochem Biophys 1994; 309:377–386.
   PubMed Web of Science ®Google Scholar
• Giorgio M, Migliaccio E, Orsini F, Paolucci D, Moroni M, Contursi C, et al. Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis. Cell 2005;122:221–233.
   PubMed Web of Science ®Google Scholar
• Dupont I, Lucas D, Clot P, Ménez C, Albano E. Cytochrome P4502E1 inducibility and hydroxyethyl radical formation among alcoholics. J Hepatol 1998;28:564–571.
   PubMed Web of Science ®Google Scholar
• Nordblom GD, Coon MJ. Hydrogen peroxide formation and stoichiometry of hydroxylation reactions catalyzed by highly purified liver microsomal cytochrome P-450. Arch Biochem Biophys 1977;180:343–347.
   PubMed Web of Science ®Google Scholar
• Gonzalez FJ. Role of cytochromes P450 in chemical toxicity and oxidative stress: studies with CYP2E1. Mutat Res 2005; 569:101–110.
   PubMed Web of Science ®Google Scholar
• De Minicis S, Brenner DA. Oxidative stress in alcoholic liver disease: role of NADPH oxidase complex. J Gastroenterol Hepatol 2008;23:S98–S103.
   Google Scholar
• Chapman RW, Morgan MY, Bell R, Sherlock S. Hepatic iron uptake in alcoholic liver disease. Gastroenterology 1983; 84:143–147.
   Google Scholar
• Whitfield JB, Zhu G, Heath AC, Powell And LW, Martin NG. Effects of alcohol consumption on indices of iron stores and of iron stores on alcohol intake markers. Alcohol Clin Exp Res 2001;25:1037–1045.
   PubMed Web of Science ®Google Scholar
• Iimuro Y, Bradford BU, Yamashina S, Rusyn I, Nakagami M, Enomoto N, et al. The glutathione precursor L-2-oxothiazolidine-4-carboxylic acid protects against liver injury due to chronic enteral ethanol exposure in the rat. Hepatology 2000;31:391–398.
   PubMed Web of Science ®Google Scholar
• Otis JS, Guidot DM. Procysteine increases alcohol-depleted glutathione stores in rat plantaris following a period of abstinence. Alcohol Alcohol 2010;45:495–500.
   PubMedGoogle Scholar
• Gauthier TW, Kable JA, Burwell L, Coles CD, Brown LA. Maternal alcohol use during pregnancy causes systemic oxidation of the glutathione redox system. Alcohol Clin Exp Res 2010;34:123–130.
   PubMedGoogle Scholar
• Fernández-Checa JC, Kaplowitz N, García-Ruiz C, Colell A, Miranda M, Marí M, et al. GSH transport in mitochondria: defense against TNF-induced oxidative stress and alcohol-induced defect. Am J Physiol 1997;273:G7–G17.
   PubMed Web of Science ®Google Scholar
• Fernandez-Checa JC, Kaplowitz N. Hepatic mitochondrial glutathione: transport and role in disease and toxicity. Toxicol Appl Pharmacol 2005;204:263–273.
   PubMed Web of Science ®Google Scholar
• Coll O, Colell A, García-Ruiz C, Kaplowitz N, Fernández-Checa JC. Sensitivity of the 2-oxoglutarate carrier to alcohol intake contributes to mitochondrial glutathione depletion. Hepatology 2003;38:692–702.
   PubMed Web of Science ®Google Scholar
• García-Ruiz C, Morales A, Ballesta A, Rodés J, Kaplowitz N, Fernández-Checa JC. Effect of chronic ethanol feeding on glutathione and functional integrity of mitochondria in periportal and perivenous rat hepatocytes. J Clin Invest 1994;94:193–201.
   PubMed Web of Science ®Google Scholar
• Hirano T, Kaplowitz N, Tsukamoto H, Kamimura S, Fernandez-Checa JC. Hepatic mitochondrial glutathione depletion and progression of experimental alcoholic liver disease in rats. Hepatology 1992;16:1423–1427.
   PubMed Web of Science ®Google Scholar
• Kaur J, Shalini S, Bansal MP. Influence of vitamin E on alcohol-induced changes in antioxidant defenses in mice liver. Toxicol Mech Methods 2010;20:82–89.
   PubMed Web of Science ®Google Scholar
• Traber MG. Vitamin E regulatory mechanisms. Annu Rev Nutr 2007;27:347–362.
   PubMed Web of Science ®Google Scholar
• Bjørneboe A, Bjørneboe GE, Hagen BF, Drevon CA. Acute and chronic effects of ethanol on secretion of alpha-tocopherol from primary cultures of rat hepatocytes. Biochim Biophys Acta 1987;922:357–363.
   PubMedGoogle Scholar
• Hartman TJ, Baer DJ, Graham LB, Stone WL, Gunter EW, Parker CE, et al. Moderate alcohol consumption and levels of antioxidant vitamins and isoprostanes in postmenopausal women. Eur J Clin Nutr 2005;59:161–168.
   PubMed Web of Science ®Google Scholar
• Valls-Belles V, Torres Mdel C, Boix L, Muñiz P, Gonzalez-Sanjose ML, Codoñer-Franch P. alpha-Tocopherol, MDA-HNE and 8-OHdG levels in liver and heart mitochondria of adriamycin-treated rats fed with alcohol-free beer. Toxicology 2008;249:97–101.
   PubMed Web of Science ®Google Scholar
• Sadrzadeh SM, Nanji AA, Meydani M. Effect of chronic ethanol feeding on plasma and liver alpha- and gamma- tocopherol levels in normal and vitamin E-deficient rats. Relationship to lipid peroxidation. Biochem Pharmacol 1994;47:2005–2010.
   PubMed Web of Science ®Google Scholar
• Sadrzadeh SM, Meydani M, Khettry U, Nanji AA. High-dose vitamin E supplementation has no effect on ethanol-induced pathological liver injury. J Pharmacol Exp Ther 1995;273:455–460.
   Google Scholar
• Nanji AA, Yang EK, Fogt F, Sadrzadeh SM, Dannenberg AJ. Medium chain triglycerides and vitamin E reduce the severity of established experimental alcoholic liver disease. J Pharmacol Exp Ther 1996;277:1694–1700.
   PubMedGoogle Scholar
• Mezey E, Potter JJ, Rennie-Tankersley L, Caballeria J, Pares A. A randomized placebo controlled trial of vitamin E for alcoholic hepatitis. J Hepatol 2004;40:40–46.
   PubMedGoogle Scholar
• Bruno RD, Njar VC. Targeting cytochrome P450 enzymes: a new approach in anti-cancer drug development. Bioorg Med Chem 2007;15:5047–5060.
   PubMed Web of Science ®Google Scholar
• Brigelius-Flohé R. Vitamin E and drug metabolism. Biochem Biophys Res Commun 2003;305:737–740.
   PubMed Web of Science ®Google Scholar
• Parker RS, Sontag TJ, Swanson JE, McCormick CC. Discovery, characterization, and significance of the cytochrome P450 omega-hydroxylase pathway of vitamin E catabolism. Ann N Y Acad Sci 2004;1031:13–21.
   PubMed Web of Science ®Google Scholar
• Minuk GY, Kelly JK, Hwang WS. Vitamin A hepatotoxicity in multiple family members. Hepatology 1988;8:272–275.
   PubMedGoogle Scholar
• Leo MA, Lieber CS. Alcohol, vitamin A, and beta-carotene: adverse interactions, including hepatotoxicity and carcinogenicity. Am J Clin Nutr 1999;69:1071–1085.
   PubMed Web of Science ®Google Scholar
• Sato M, Lieber CS. Increased metabolism of retinoic acid after chronic ethanol consumption in rat liver microsomes. Arch Biochem Biophys. 1982;213:557–564.
   PubMed Web of Science ®Google Scholar
• Dan Z, Popov Y, Patsenker E, Preimel D, Liu C, Wang XD, et al. Hepatotoxicity of alcohol-induced polar retinol metabolites involves apoptosis via loss of mitochondrial membrane potential. FASEB J 2005;19:845–847.
   Google Scholar
• Wang XD. Alcohol, vitamin A, and cancer. Alcohol 2005;35:251–258.
   PubMed Web of Science ®Google Scholar
• Rouach H, Houzé P, Gentil M, Orfanelli MT, Nordmann R. Changes in some pro- and antioxidants in rat cerebellum after chronic alcohol intake. Biochem Pharmacol 1997; 53:539–545.
   Google Scholar
• Polavarapu R, Spitz DR, Sim JE, Follansbee MH, Oberley LW, Rahemtulla A, Nanji AA. Increased lipid peroxidation and impaired antioxidant enzyme function is associated with pathological liver injury in experimental alcoholic liver disease in rats fed diets high in corn oil and fish oil. Hepatology 1998;27:1317–1323.
   PubMed Web of Science ®Google Scholar
• Kessova IG, Ho YS, Thung S, Cederbaum AI. Alcohol- induced liver injury in mice lacking Cu, Zn-superoxide dismutase. Hepatology 2003;38:1136–1145.
   PubMed Web of Science ®Google Scholar
• Kessova IG, Cederbaum AI. Mitochondrial alterations in livers of Sod1-/- mice fed alcohol. Free Radic Biol Med 2007; 42:1470–1480.
   PubMedGoogle Scholar
• Wheeler MD, Kono H, Yin M, Rusyn I, Froh M, Connor HD, et al. Delivery of the Cu/Zn-superoxide dismutase gene with adenovirus reduces early alcohol-induced liver injury in rats. Gastroenterology 2001;120:1241–1250.
   PubMed Web of Science ®Google Scholar
• Adachi M, Ishii H. Role of mitochondria in alcoholic liver injury. Free Radic Biol Med 2002;32:487–491.
   PubMedGoogle Scholar
• Albano E. Alcohol, oxidative stress and free radical damage. Proc Nutr Soc 2006;65:278–290.
   PubMed Web of Science ®Google Scholar
• Lee YH, Lin Q, Boelsterli UA, Chung MC. The Sod2 mutant mouse as a model for oxidative stress: a functional proteomics perspective. Mass Spectrom Rev 2010;29:179–196.
   Google Scholar
• Sutton A, Khoury H, Prip-Buus C, Cepanec C, Pessayre D, Degoul F. The Ala16Val genetic dimorphism modulates the import of human manganese superoxide dismutase into rat liver mitochondria. Pharmacogenetics 2003;13:145–157.
   PubMedGoogle Scholar
• Namikawa C, Shu-Ping Z, Vyselaar JR, Nozaki Y, Nemoto Y, Ono M, et al. Polymorphisms of microsomal triglyceride transfer protein gene and manganese superoxide dismutase gene in non-alcoholic steatohepatitis. J Hepatol 2004;40:781–786.
   PubMed Web of Science ®Google Scholar
• Stewart SF, Leathart JB, Chen Y, Daly AK, Rolla R, Vay D, et al. Valine-alanine manganese superoxide dismutase polymorphism is not associated with alcohol-induced oxidative stress or liver fibrosis. Hepatology 2002;36:1355–1360.
   PubMed Web of Science ®Google Scholar
• Brind A, Fryer A, Hurlstone A, Fisher N, Pirmohamed M. The role of polymorphism in manganese superoxide dismutase in susceptibility to alcoholic liver disease. Gastroenterology 2003;124:2000–2002.
   Google Scholar
• Bailey SM. A review of the role of reactive oxygen and nitrogen species in alcohol-induced mitochondrial dysfunction. Free Radic Res 2003;37:585–596.
   PubMed Web of Science ®Google Scholar
• Miñana JB, Gómez-Cambronero L, Lloret A, Pallardó FV, Del Olmo J, Escudero A, et al. Mitochondrial oxidative stress and CD95 ligand: a dual mechanism for hepatocyte apoptosis in chronic alcoholism. Hepatology 2002;35:1205–1214.
   PubMed Web of Science ®Google Scholar
• Miyamoto K, French SW. Hepatic adenosine in rats fed ethanol: effect of acute hyperoxia or hypoxia. Alcohol Clin Exp Res 1988;12:512–515.
   Google Scholar
• Takahashi H, Geoffrion Y, Butler KW, French SW. In vivo hepatic energy metabolism during the progression of alcoholic liver disease: a noninvasive 31P nuclear magnetic resonance study in rats. Hepatology 1990;11:65–73.
   Google Scholar
• Gyamfi D, Everitt HE, Tewfik I, Clemens DL, Patel VB. Hepatic mitochondrial dysfunction induced by fatty acids and ethanol. Free Radic Biol Med 2012;53: 2131–2145.
   Google Scholar
• Hoek JB, Cahill A, Pastorino JG. Alcohol and mitochondria: a dysfunctional relationship. Gastroenterology 2002; 122:2049–2063.
   PubMed Web of Science ®Google Scholar
• Mansouri A, Fromenty B, Berson A, Robin MA, Grimbert S, Beaugrand M, et al. Multiple hepatic mitochondrial DNA deletions suggest premature oxidative aging in alcoholic patients. J Hepatol 1997;27:96–102.
   PubMed Web of Science ®Google Scholar
• Coleman WB, Cunningham CC. Effects of chronic ethanol consumption on the synthesis of polypeptides encoded by the hepatic mitochondrial genome. Biochim Biophys Acta 1990; 1019:142–150.
   PubMedGoogle Scholar
• Venkatraman A, Landar A, Davis AJ, Chamlee L, Sanderson T, Kim H, et al. Modification of the mitochondrial proteome in response to the stress of ethanol-dependent hepatotoxicity. J Biol Chem 2004;279:22092–22101.
   PubMed Web of Science ®Google Scholar
• Cahill A, Cunningham CC. Effects of chronic ethanol feeding on the protein composition of mitochondrial ribosomes. Electrophoresis 2000;21:3420–3426.
   Google Scholar
• Patel VB, Cunningham CC. Altered hepatic mitochondrial ribosome structure following chronic ethanol consumption. Arch Biochem Biophys 2002;398:41–50.
   PubMed Web of Science ®Google Scholar
• Moon KH, Hood BL, Kim BJ, Hardwick JP, Conrads TP, Veenstra TD, Song BJ. Inactivation of oxidized and S-nitrosylated mitochondrial proteins in alcoholic fatty liver of rats. Hepatology 2006;44:1218–1230.
   PubMed Web of Science ®Google Scholar
• Robin MA, Sauvage I, Grandperret T, Descatoire V, Pessayre D, Fromenty B. Ethanol increases mitochondrial cytochrome P450 2E1 in mouse liver and rat hepatocytes. FEBS Lett 2005;579:6895–6902.
   PubMed Web of Science ®Google Scholar
• Tretter L, Adam-Vizi V. Generation of reactive oxygen species in the reaction catalyzed by alpha-ketoglutarate dehydrogenase. J Neurosci 2004;24:7771–7778.
   PubMed Web of Science ®Google Scholar
• Tretter L, Takacs K, Hegedus V, Adam-Vizi V. Characteristics of alpha-glycerophosphate-evoked H2O2 generation in brain mitochondria. J Neurochem 2007;100:650–663.
   Google Scholar
• Mantena SK, King AL, Andringa KK, Eccleston HB, Bailey SM. Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases. Free Radic Biol Med 2008;44:1259–1272.
   PubMed Web of Science ®Google Scholar
• Colell A, García-Ruiz C, Miranda M, Ardite E, Marí M, Morales A, et al. Selective glutathione depletion of mitochondria by ethanol sensitizes hepatocytes to tumor necrosis factor. Gastroenterology 1998;115:1541–1551.
   PubMed Web of Science ®Google Scholar
• Pastorino JG, Hoek JB. Ethanol potentiates tumor necrosis factor-alpha cytotoxicity in hepatoma cells and primary rat hepatocytes by promoting induction of the mitochondrial permeability transition. Hepatology 2000;31:1141–1152.
   PubMed Web of Science ®Google Scholar
• Han D, Hanawa N, Saberi B, Kaplowitz N. Mechanisms of liver injury. III. Role of glutathione redox status in liver injury. Am J Physiol Gastrointest Liver Physiol 2006;291:G1–G7.
   PubMed Web of Science ®Google Scholar
• Garcia-Ruiz C, Fernandez-Checa JC. Mitochondrial glutathione: hepatocellular survival-death switch. J Gastroenterol Hepatol 2006;21:S3–S6.
   PubMed Web of Science ®Google Scholar
• Zhou Z, Wang L, Song Z, Lambert JC, McClain CJ, Kang YJ. A critical involvement of oxidative stress in acute alcohol-induced hepatic TNF-alpha production. Am J Pathol 2003;163:1137–1146.
   PubMed Web of Science ®Google Scholar
• Sozio M, Crabb DW. Alcohol and lipid metabolism. Am J Physiol Endocrinol Metab 2008;295:E10–E16.
   Google Scholar
• Arteel GE. Oxidants and antioxidants in alcohol-induced liver disease. Gastroenterology 2003;124:778–790.
   PubMed Web of Science ®Google Scholar
• Albano E. Oxidative mechanisms in the pathogenesis of alcoholic liver disease. Mol Aspects Med 2008;29:9–16.
   PubMed Web of Science ®Google Scholar
• Donohue TM Jr. Alcohol-induced steatosis in liver cells. World J Gastroenterol 2007;13:4974–4978.
   Google Scholar
• Lu Y, Zhuge J, Wu D, Cederbaum AI. Ethanol induction of CYP2A5: permissive role for CYP2E1. Drug Metab Dispos 2011;39:330–336.
   Google Scholar
• Lu Y, Zhang XH, Cederbaum AI. Ethanol induction of CYP2A5: role of CYP2E1-ROS-Nrf2 pathway. Toxicol Sci 2012;128:427–438.
   Google Scholar
• Wu KC, Liu J, Klaassen CD. Role of Nrf2 in preventing ethanol-induced oxidative stress and lipid accumulation. Toxicol Appl Pharmacol 2012;262:321–329.
   PubMed Web of Science ®Google Scholar
• Supakul R, Liangpunsakul S. Alcoholic-induced hepatic steatosis–role of ceramide and protein phosphatase 2A. Transl Res 2011;158:77–81.
   Google Scholar
• You M, Matsumoto M, Pacold CM, Cho WK, Crabb DW. The role of AMP-activated protein kinase in the action of ethanol in the liver. Gastroenterology 2004;127: 1798–1808.
   PubMed Web of Science ®Google Scholar
• Fernandez-Checa JC, Colell A, Mari M, García-Ruiz C. Ceramide, tumor necrosis factor and alcohol-induced liver disease. Alcohol Clin Exp Res 2005;29:151S–157S.
   Google Scholar
• Powell EE, Jonsson JR, Clouston AD. Steatosis: co-factor in other liver diseases. Hepatology 2005;42:5–13.
   PubMed Web of Science ®Google Scholar
• Sozio MS, Liangpunsakul S, Crabb D. The role of lipid metabolism in the pathogenesis of alcoholic and nonalcoholic hepatic steatosis. Semin Liver Dis 2010;30:378–390.
   PubMed Web of Science ®Google Scholar
• Ji C, Kaplowitz N. Betaine decreases hyperhomocysteinemia, endoplasmic reticulum stress, and liver injury in alcohol-fed mice. Gastroenterology 2003;124:1488–1499.
   PubMed Web of Science ®Google Scholar
• Ji C. Mechanisms of alcohol-induced endoplasmic reticulum stress and organ injuries. Biochem Res Int 2012; 2012:216450.
   PubMedGoogle Scholar
• Malhi H, Kaufman RJ. Endoplasmic reticulum stress in liver disease. J Hepatol 2011;54:795–809.
   PubMed Web of Science ®Google Scholar
• Rutkowski DT, Wu J, Back SH, Callaghan MU, Ferris SP, Iqbal J, et al. UPR pathways combine to prevent hepatic steatosis caused by ER stress-mediated suppression of transcriptional master regulators. Dev Cell 2008;15:829–840.
   PubMed Web of Science ®Google Scholar
• Ron D, Hubbard SR. How IRE1 reacts to ER stress. Cell 2008;132:24–26.
   PubMed Web of Science ®Google Scholar
• Lee AH, Scapa EF, Cohen DE, Glimcher LH. Regulation of hepatic lipogenesis by the transcription factor XBP1. Science 2008;320:1492–1496.
   PubMed Web of Science ®Google Scholar
• Rao RK, Seth A, Sheth P. Recent Advances in Alcoholic Liver Disease I. Role of intestinal permeability and endotoxemia in alcoholic liver disease. Am J Physiol Gastrointest Liver Physiol 2004;286:G881–G884.
   PubMed Web of Science ®Google Scholar
• Hines IN, Wheeler MD. Recent advances in alcoholic liver disease III. Role of the innate immune response in alcoholic hepatitis. Am J Physiol Gastrointest Liver Physiol 2004;287:G310–G314.
   PubMed Web of Science ®Google Scholar
• Uesugi T, Froh M, Arteel GE, Bradford BU, Thurman RG. Toll-like receptor 4 is involved in the mechanism of early alcohol-induced liver injury in mice. Hepatology 2001;34: 101–108.
   PubMed Web of Science ®Google Scholar
• Thakur V, Pritchard MT, McMullen MR, Wang Q, Nagy LE. Chronic ethanol feeding increases activation of NADPH oxidase by lipopolysaccharide in rat Kupffer cells: role of increased reactive oxygen in LPS-stimulated ERK1/2 activation and TNF-alpha production. J Leukoc Biol 2006;79: 1348–1356.
   PubMed Web of Science ®Google Scholar
• Park HS, Jung HY, Park EY, Kim J, Lee WJ, Bae YS. Cutting edge: direct interaction of TLR4 with NAD(P)H oxidase 4 isozyme is essential for lipopolysaccharide-induced production of reactive oxygen species and activation of NF-kappa B. J Immunol 2004;173:3589–3593.
   PubMed Web of Science ®Google Scholar
• Dasu MR, Devaraj S, Zhao L, Hwang DH, Jialal I. High glucose induces toll-like receptor expression in human monocytes: mechanism of activation. Diabetes 2008;57:3090–3098.
   PubMed Web of Science ®Google Scholar
• Kono H, Rusyn I, Yin M, Gäbele E, Yamashina S, Dikalova A, et al. NADPH oxidase-derived free radicals are key oxidants in alcohol-induced liver disease. J Clin Invest 2000;106:867–872.
   PubMed Web of Science ®Google Scholar
• Cao Q, Mak KM, Lieber CS. Dilinoleoylphosphatidylcholine decreases LPS-induced TNF-alpha generation in Kupffer cells of ethanol-fed rats: respective roles of MAPKs and NF-kappaB. Biochem Biophys Res Commun 2002;294:849–853.
   PubMedGoogle Scholar
• Gustot T, Lemmers A, Moreno C, Nagy N, Quertinmont E, Nicaise C, et al. Differential liver sensitization to toll-like receptor pathways in mice with alcoholic fatty liver. Hepatology 2006;43:989–1000.
   PubMedGoogle Scholar
• Mandrekar P, Szabo G. Signalling pathways in alcohol- induced liver inflammation. J Hepatol 2009;50:1258–1266.
   PubMed Web of Science ®Google Scholar
• Schuppan D. Structure of the extracellular matrix in normal and fibrotic liver: collagens and glycoproteins. Semin Liver Dis 1990;10:1–10.
   PubMedGoogle Scholar
• Friedman SL. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem 2000;275:2247–2250.
   PubMed Web of Science ®Google Scholar
• George J, Rao KR, Stern R, Chandrakasan G. Dimethylnitrosamine-induced liver injury in rats: the early deposition of collagen. Toxicology 2001;156:129–138.
   PubMed Web of Science ®Google Scholar
• Bissell DM. Cell-matrix interaction and hepatic fibrosis. Prog Liver Dis 1990;9:143–155.
   PubMedGoogle Scholar
• George J, Chandrakasan G. Biochemical abnormalities during the progression of hepatic fibrosis induced by dimethylnitrosamine. Clin Biochem 2000;33:563–570.
   PubMed Web of Science ®Google Scholar
• Gressner AM. Transdifferentiation of hepatic stellate cells (Ito cells) to myofibroblasts: a key event in hepatic fibrogenesis. Kidney Int Suppl 1996;54:S39–S45.
   PubMedGoogle Scholar
• Nieto N. Oxidative-stress and IL-6 mediate the fibrogenic effects of Kupffer cells on stellate cells. Hepatology 2006; 44:1487–1501.
   PubMed Web of Science ®Google Scholar
• Tsukamoto H. Cytokine regulation of hepatic stellate cells in liver fibrosis. Alcohol Clin Exp Res 1999;23:911–916.
   PubMed Web of Science ®Google Scholar
• Tilg H, Hotamisligil GS. Nonalcoholic fatty liver disease: cytokine-adipokine interplay and regulation of insulin resistance. Gastroenterology 2006;131:934–945.
   PubMed Web of Science ®Google Scholar
• Bataller R, Brenner DA. Liver fibrosis. J Clin Invest 2005;115:209–218.
   PubMed Web of Science ®Google Scholar
• De Minicis S, Bataller R, Brenner DA. NADPH oxidase in the liver: defensive, offensive, or fibrogenic?Gastroenterology 2006;131:272–275.
   PubMed Web of Science ®Google Scholar
• Bataller R, Schwabe RF, Choi YH, Yang L, Paik YH, Lindquist J, et al. NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis. J Clin Invest 2003;112:1383–1394.
   PubMed Web of Science ®Google Scholar
• Adachi T, Togashi H, Suzuki A, Kasai S, Ito J, Sugahara K, Kawata S. NAD(P)H oxidase plays a crucial role in PDGF-induced proliferation of hepatic stellate cells. Hepatology 2005;41:1272–1281.
   PubMed Web of Science ®Google Scholar
• Hasegawa T, Kikuyama M, Sakurai K, Kambayashi Y, Adachi M, Saniabadi AR, et al. Mechanism of superoxide anion production by hepatic sinusoidal endothelial cells and Kupffer cells during short-term ethanol perfusion in the rat. Liver 2002;22:321–329.
   Google Scholar
• Polikandriotis JA, Rupnow HL, Elms SC, Clempus RE, Campbell DJ, Sutliff RL, et al. Chronic ethanol ingestion increases superoxide production and NADPH oxidase expression in the lung. Am J Respir Cell Mol Biol 2006;34: 314–319.
   Google Scholar
• Wang X, Ke Z, Chen G, Xu M, Bower KA, Frank JA, et al. Cdc42-dependent activation of NADPH oxidase is involved in ethanol-induced neuronal oxidative stress. PLoS One 2012;7:e38075.
   Google Scholar
• Dong J, Sulik KK, Chen SY. The role of NOX enzymes in ethanol-induced oxidative stress and apoptosis in mouse embryos. Toxicol Lett 2010;193:94–100.
   PubMed Web of Science ®Google Scholar
• Nieto N, Friedman SL, Cederbaum AI. Stimulation and proliferation of primary rat hepatic stellate cells by cytochrome P450 2E1-derived reactive oxygen species. Hepatology 2002;35:62–73.
   PubMed Web of Science ®Google Scholar
• George J, Pera N, Phung N, Leclercq I, Yun Hou J, Farrell G. Lipid peroxidation, stellate cell activation and hepatic fibrogenesis in a rat model of chronic steatohepatitis. J Hepatol 2003;39:756–764.
   PubMed Web of Science ®Google Scholar