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Oxidative Stress and Inflammation: Essential Partners in Alcoholic Liver Disease

By Aditya Ambade and Pranoti Mandrekar


Alcoholic liver disease (ALD) is a multifaceted disease that is characterized by hepatic steatosis or fat deposition and hepatitis or inflammation. Over the past decade, multiple lines of evidence have emerged on the mechanisms associated with ALD. The key mechanisms identified so far are sensitization to gut-derived endotoxin/lipopolysaccharide resulting in proinflammatory cytokine production and cellular stress due to oxidative processes, contributing to the development and progression of disease. While oxidative stress and inflammatory responses are studied independently in ALD, mechanisms linking these two processes play a major role in pathogenesis of disease. Here we review major players of oxidative stress and inflammation and highlight signaling intermediates regulated by oxidative stress that provokes proinflammatory responses in alcoholic liver disease

Topics: Review Article
Publisher: Hindawi Publishing Corporation
OAI identifier: oai:pubmedcentral.nih.gov:3303590
Provided by: PubMed Central
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    1. (2005). A central role for the Hsp90·Cdc37 molecular chaperone module in interleukin1 receptor-associated-kinase-dependent signaling by Toll-like receptors,”
    2. (2010). A clear and present danger: endogenous ligands of Toll-like receptors,”
    3. (1996). a l a b r e s e ,M .R e n i s ,A .C a l d e r o n e ,A .R u s s o ,M .L .B a r c e l
    4. (2001). A non-toxic heat shock protein 70 inducer,8 International Journal of Hepatology geranylgeranylacetone, suppresses apoptosis of cultured rat hepatocytes caused by hydrogen peroxide and ethanol,”
    5. (2009). Activation of MEK 1/2 and p42/44 MAPK by angiotensin II in hepatocyte nucleus and their potentiation by ethanol,” Alcohol,v o l .4 3 ,n o .4 ,p p .
    6. (2006). Alcohol and lipid metabolism,”
    7. (2002). Alcohol and mitochondria: a dysfunctional relationship,”
    8. (2008). Alcohol exposure regulates heat shock transcription factor binding and heat shock proteins 70 and 90 in monocytes and macrophages: implication for TNF-α regulation,”
    9. (2001). Alcohol-induced free radicals in mice: direct toxicants or signaling molecules?”
    10. (2003). Alcohol, oxidative stress, and free radical damage,”
    11. (2000). Alcohol: its metabolism and interaction with nutrients,”
    12. (2010). Alcoholic hepatitis 2010: a clinician’s guide to diagnosis and therapy,”
    13. (2010). Analysis of the liver mitochondrial proteome in response to ethanol and S-adenosylmethionine treatments: novel molecular targets of disease andhepatoprotection,”
    14. and Egr-1 contribute to increased TNF-α production in rat Kupffer cells after chronic ethanol feeding,”
    15. (2010). Anti-inflammatory and anti-apoptotic roles of endothelial cell
    16. (2009). Autophagy and ethanol-induced liver injury,”
    17. (2003). Betaine decreases hyperhomocysteinemia, endoplasmic reticulum stress, and liver injury in alcohol-fed mice,”
    18. (2008). C h a u n g ,A .J a c o b ,Y .J i ,a n dP .W a n g ,“ S u p p r e s s i o n of PGC-1alpha by ethanol: implications of its role in alcohol induced liver injury,”
    19. (2008). Cell type-dependent pro- and anti-inflammatory role of signal transducer and activator of transcription 3 in alcoholic liver injury,”
    20. (2010). Chronic alcohol-induced liver injury and oxidant stress are decreased in cytochrome P4502E1 knockout mice and restored
    21. (2010). Chronic ethanol consumption results in atypical liver injury in copper/zinc superoxide dismutase deficient mice,” Alcoholism:
    22. (2002). Chronic ethanol exposure potentiates lipopolysaccharide liver injury despite inhibiting Jun N-terminal kinase and caspase 3 activation,”
    23. (2006). 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-α production,” J o u r n a lo fL e u k o c y t e Biology,
    24. (2002). Chronic ethanol increases lipopolysaccharide-stimulated Egr-1 expression in RAW 264.7 macrophages. Contribution to enhanced tumor necrosis factor α production,”
    25. (2003). Combined exposure to m-xylene and ethanol: oxidative stress in the rat liver,”
    26. (1994). Covalent protein adducts in the liver as a result of ethanol metabolism and lipid peroxidation,”
    27. (2001). CYP2E1-dependent toxicity and oxidative stress in
    28. (2008). Cytochrome P450 2E1 contributes to ethanol-induced fatty liver in mice,”
    29. (2002). D.J.Tuma,“Roleofmalondialdehyde-acetaldehydeadductsin liver injury,” Free Radical Biology and Medicine,
    30. (2005). DNA adducts from acetaldehyde: implications for alcohol-related carcinogenesis,”
    31. (2001). e s u g i ,M .F r o h ,G .E .A r t e e l ,B .U .B r a d f o r d ,a n dR .G . Thurman, “Toll-like receptor 4 is involved in the mechanism of early alcohol-induced liver injury in mice,” Hepatology,
    32. (2008). Effect of chronic alcohol consumption on Hepatic
    33. (2002). Effects of alcohol and oxidative stress on liver pathology: the role of the mitochondrion,”
    34. (2010). Elevated mitochondrial reactive oxygen species generation affects the immune response via hypoxia-inducible factor-1α in longlived Mclk1+/− mouse mutants,”
    35. (2003). Endotoxin and kupffer cell activation in alcoholic liver disease,”
    36. (2001). Ethanol consumption and liver mitochondria function,”
    37. (2000). Ethanol potentiates tumor necrosis factor-α cytotoxicity in hepatoma cells and primary rat hepatocytes by promoting induction of the mitochondrial permeability transition,”
    38. (2005). Ethanol-induced sensitization to endotoxin in Kupffer cells is dependent upon oxidative stress,” Alcoholism:
    39. (2009). Formation of γ-ketoaldehydeprotein adducts during ethanol-induced liver injury
    40. (2002). Free radicals in the physiological control of cell function,”
    41. (2003). Geldanamycin treatment ameliorates the response to LPS in murine macrophages by decreasing CD14 surface expression,”
    42. (2006). h i a n g ,O .D a n g ,K .A n d e r s o n ,A .M a t s u z a w a ,H .I c h i j o
    43. (1999). Iimuro et al., “Mechanisms of alcohol-induced hepatotoxicity: studies in rats,”
    44. (2008). Impaired receptor-mediated endocytosis: its role in alcoholinduced apoptosis,”
    45. (2006). Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation,”
    46. (2001). Lipopolysaccharide stimulates the MyaD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes,”
    47. (2003). LPS-TLR4 signaling to IRF-3/7 and NF-κBi n v o l v e st h et o l la d a p t e r s TRAM and TRIF,”
    48. (2007). Lysosomal leakage andlack ofadaptation ofhepatoprotective enzyme contribute to enhanced susceptibility to ethanolinduced liver injury in female rats,”
    49. (2004). Malondialdehyde-acetaldehyde (MAA) modified proteins induce pro-inflammatory and pro-fibrotic responses by liver endothelial cells,”
    50. (2011). Mitochondrial reactive oxygen species drive proinflammatory cytokine production,”
    51. (2001). Mitogen-activated protein kinase p38 controls the expression and posttranslational modification of tristetraprolin, a regulator of tumor necrosis factor alpha mRNA stability,” Molecular and Cellular Biology,
    52. (2005). Molecular links between aging and adipose tissue,”
    53. (2008). N2-ethyldeoxyguanosine as a potential biomarker for assessing effects of alcohol consumption
    54. (2000). NADPH oxidase-derived free radicals are key oxidants in alcohol-induced liver disease,”
    55. (1998). NF-κB and rel proteins: evolutionarily conserved mediators of immune responses,”
    56. (2011). Nitric oxide and hypoxia exacerbate alcohol-induced mitochondrial dysfunctioninhepatocytes,”BiochimicaetBiophysicaActa,vol.
    57. (2007). Novel interactions of mitochondria and reactive oxygen/nitrogen species in alcoholInternational
    58. (2005). Nutrient control of glucose homeostasis through a complex of PGC-1α and
    59. (2000). Oxidants, oxidative stress and the biology of ageing,”
    60. (2007). Oxidative stress and aberrant signaling in aging and cognitive decline,”
    61. (2005). Oxidative stress and signal transduction pathways in alcoholic liver disease,”
    62. (2004). P a r k ,H .Y .J u n g ,E .Y .P a r k
    63. (2003). P a s t o r i n o ,N .S h u l g a ,a n dJ .B .H o e k ,“ T N F - α-induced cell death in ethanol-exposed cells depends on p38 MAPK signaling but is independent of Bid and caspase-8,”
    64. (2006). Pattern recognition receptors: a contemporary view on liver diseases,”
    65. (2003). Peroxisome proliferator-activated receptor α (PPARα) agonist treatment reverses PPARα dysfunction and abnormalities in hepatic lipid metabolism in ethanol-fed mice,”
    66. (2006). Predominant role of sterol response element binding proteins (SREBP) lipogenic pathways in hepatic steatosis in the murine intragastric ethanol feeding model,”
    67. (2003). Recent insights into the role of the innate immune system in the development of alcoholic liver disease,”
    68. (2001). Reduced early alcohol-induced liver injury in CD14-deficient mice,”
    69. (2010). Regulation of innate immune responses by autophagy-related proteins,” J o u r n a lo fC e l l Biology,
    70. (2011). Regulation of innate immunity by signaling pathways emerging from the endoplasmic reticulum,”
    71. (2004). Requirement of Hsp90 activity for IκB kinase (IKK) biosynthesis and for constitutive and inducible
    72. sensitizes the liver to LPS- and TNF α-induced toxicity via elevatedoxidativeandnitrosativestressandactivationofASK1 and JNK mitogen-activated kinases,”
    73. (2009). Signalling pathways
    74. (2001). Stabilization o ft u m o rn e c r o s i sf a c t o rα mRNA by chronic ethanol: role of A+U-rich elements and p38 mitogen-activated protein kinase signaling pathway,”
    75. (2010). The anti-inflammatory effects of adiponectin are mediated via a heme oxygenase-1-dependent pathway in rat kupffer cells,”
    76. (2008). The critical role of toll-like receptor (TLR) 4
    77. (2007). The grateful dead: damage-associated molecular pattern molecules and reduction/oxidation regulate immunity,”
    78. (2009). The opposite effects of acute and chronic alcohol on lipopolysaccharide-inducedinflammationarelinkedtoIRAKM in human monocytes,”
    79. (2007). Toll-like receptor 4 is a sensor for autophagy associated with innate immunity,”
    80. (2007). Toll-like receptors and type I Interferons,”
    81. (2005). Toll-like receptors in innate immunity,”
    82. (2008). TRIF and IRF-3 binding to the TNF promoter results in macrophage TNF dysregulation and steatosis induced by chronic ethanol,”
    83. (2006). u s t o t ,A .L e m m e r s ,C .M o r e n oe ta l . ,“ D i fferential liver sensitization to toll-like receptor pathways in mice with alcoholic fatty liver,”
    84. (2006). Unfolding new mechanisms of alcoholic liver disease in the endoplasmic reticulum,”
    85. (1998). V.Calabrese,M.Renis,A.Calderoneetal.,“Stressproteinsand SH-groups in oxidant-induced cellular injury after chronic ethanol administration in rat,”
    86. (2008). Y.LuandA.I.Cederbaum,“CYP2E1andoxidativeliverinjury by alcohol,” Free Radical Biology and Medicine,

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