CoChat
Sign Up
Cited by 648Liver Disease Diagnosis and TreatmentLiver physiology and pathologyDrug-Induced Hepatotoxicity and Protection

Role of Oxidative Stress in Pathophysiology of Nonalcoholic Fatty Liver Disease

Open access
Masarone, Mario, Rosato, Valerio, Dallio, Marcello, Gravina, Antonietta Gerarda, Aglitti, Andrea, Loguercio, Carmelina, Federico, Alessandro, Persico, Marcello·2018·Oxidative Medicine and Cellular Longevity
DOI 10.1155/2018/9547613PMC PMC6016172
Open this paper in CoChat — free accountOpen PDF

Abstract

Liver steatosis without alcohol consumption, namely, nonalcoholic fatty liver disease (NAFLD), is a common hepatic condition that encompasses a wide spectrum of presentations, ranging from simple accumulation of triglycerides in the hepatocytes without any liver damage to inflammation, necrosis, ballooning, and fibrosis (namely, nonalcoholic steatohepatitis) up to severe liver disease and eventually cirrhosis and/or hepatocellular carcinoma. The pathophysiology of fatty liver and its progression is influenced by multiple factors (environmental and genetics), in a “multiple parallel‐hit model,” in which oxidative stress plays a very likely primary role as the starting point of the hepatic and extrahepatic damage. The aim of this review is to give a comprehensive insight on the present researches and findings on the role of oxidative stress mechanisms in the pathogenesis and pathophysiology of NAFLD. With this aim, we evaluated the available data in basic science and clinical studies in this field, reviewing the most recent works published on this topic.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1155/2018/9547613

Cites

20 of 20 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • An increase in ROS formation is accompanied by decrease in the levels of glutathione, MnSOD and Catalase.

    “An increase in ROS formation was accompanied by decrease in the levels of glutathione, MnSOD and Catalase [31].”

    From Intervention by picroside II on FFAs induced lipid accumulation and lipotoxicity in HepG2 cells (2021) · cites this paper as [31]

    Section 2.1 reports that, in a high-fat-diet mouse model, increased oxidative stress was associated with lower glutathione levels and reduced catalase and superoxide-dismutase activity. Section 2 separately links reduced MnSOD activity to increased ROS production. The paper supports the general association, but it does not report decreased MnSOD and catalase levels together with increased ROS; it discusses enzyme activity, and the findings come from different contexts. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 98

  1. [1]Angulo P. Nonalcoholic fatty liver disease The New England Journal of Medicine 2002 346 16 1221 1231 10.1056/NEJMra011775 2-s2.0-0037129380 11961152 · DOI · Paper page
  2. [2]Bedogni G. Miglioli L. Masutti F. Tiribelli C. Marchesini G. Bellentani S. Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study Hepatology 2005 42 1 44 52 10.1002/hep.20734 2-s2.0-21344449292 15895401 · DOI
  3. [3]Masarone M. Federico A. Abenavoli L. Loguercio C. Persico M. Non alcoholic fatty liver: epidemiology and natural history Reviews on Recent Clinical Trials 2014 9 3 126 133 25514916
  4. [5]Brunt E. M. Pathology of nonalcoholic fatty liver disease Nature Reviews Gastroenterology & Hepatology 2010 7 4 195 203 10.1038/nrgastro.2010.21 2-s2.0-77950858243 20195271 · DOI · Paper page
  5. [6]Nascimbeni F. Pais R. Bellentani S. From NAFLD in clinical practice to answers from guidelines Journal of Hepatology 2013 59 4 859 871 10.1016/j.jhep.2013.05.044 2-s2.0-84884419004 23751754 · DOI
  6. [7]Ertle J. Dechêne A. Sowa J. P. Non-alcoholic fatty liver disease progresses to hepatocellular carcinoma in the absence of apparent cirrhosis International Journal of Cancer 2011 128 10 2436 2443 10.1002/ijc.25797 2-s2.0-79953185045 21128245 · DOI
  7. [8]Masarone M. Rosato V. Aglitti A. Liver biopsy in type 2 diabetes mellitus: steatohepatitis represents the sole feature of liver damage PLoS One 2017 12 6, article e0178473 10.1371/journal.pone.0178473 2-s2.0-85020175200 28570615 PMC5453539 · DOI
  8. [10]Vos B. Moreno C. Nagy N. Lean non-alcoholic fatty liver disease (lean-NAFLD): a major cause of cryptogenic liver disease Acta Gastroenterologica Belgica 2011 74 3 389 394 22103042
  9. [11]Podrini C. Borghesan M. Greco A. Pazienza V. Mazzoccoli G. Vinciguerra M. Redox homeostasis and epigenetics in non-alcoholic fatty liver disease (NAFLD) Current Pharmaceutical Design 2013 19 15 2737 2746 10.2174/1381612811319150009 2-s2.0-84876727580 23092327 · DOI
  10. [12]Pirola C. J. Gianotti T. F. Burgueno A. L. Epigenetic modification of liver mitochondrial DNA is associated with histological severity of nonalcoholic fatty liver disease Gut 2013 62 9 1356 1363 10.1136/gutjnl-2012-302962 2-s2.0-84881546730 22879518 · DOI · Paper page
  11. [13]Lakka H. M. Laaksonen D. E. Lakka T. A. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men JAMA 2002 288 21 2709 2716 10.1001/jama.288.21.2709 2-s2.0-0037021505 12460094 · DOI · Paper page
  12. [14]Petta S. Gastaldelli A. Rebelos E. Pathophysiology of non alcoholic fatty liver disease International Journal of Molecular Sciences 2016 17 12, article 2082 10.3390/ijms17122082 2-s2.0-85006134935 27973438 PMC5187882 · DOI
  13. [15]Pasarin M. Abraldes J. G. Liguori E. Kok B. La Mura V. Intrahepatic vascular changes in non-alcoholic fatty liver disease: potential role of insulin-resistance and endothelial dysfunction World Journal of Gastroenterology 2017 23 37 6777 6787 10.3748/wjg.v23.i37.6777 2-s2.0-85030097485 29085222 PMC5645612 · DOI
  14. [16]Day C. P. James OF Steatohepatitis: a tale of two “hits”? Gastroenterology 1998 114 4 842 845 10.1016/S0016-5085(98)70599-2 2-s2.0-0031947715 9547102 · DOI · Paper page
  15. [18]Caldwell S. H. Swerdlow R. H. Khan E. M. Mitochondrial abnormalities in non-alcoholic steatohepatitis Journal of Hepatology 1999 31 3 430 434 10.1016/S0168-8278(99)80033-6 2-s2.0-0033198978 10488700 · DOI
  16. [19]Grattagliano I. de Bari O. Bernardo T. C. Oliveira P. J. Wang D. Q. Portincasa P. Role of mitochondria in nonalcoholic fatty liver disease-from origin to propagation Clinical Biochemistry 2012 45 9 610 618 10.1016/j.clinbiochem.2012.03.024 2-s2.0-84861230299 22484459 · DOI
  17. [20]Begriche K. Massart J. Robin M. A. Bonnet F. Fromenty B. Mitochondrial adaptations and dysfunctions in nonalcoholic fatty liver disease Hepatology 2013 58 4 1497 1507 10.1002/hep.26226 2-s2.0-84884984539 23299992 · DOI · Paper page
  18. [21]Seki S. Kitada T. Yamada T. Sakaguchi H. Nakatani K. Wakasa K. In situ detection of lipid peroxidation and oxidative DNA damage in non-alcoholic fatty liver diseases Journal of Hepatology 2002 37 1 56 62 10.1016/S0168-8278(02)00073-9 2-s2.0-0035991444 12076862 · DOI
  19. [22]Silva M. F. Aires C. C. Luis P. B. Valproic acid metabolism and its effects on mitochondrial fatty acid oxidation: a review Journal of Inherited Metabolic Disease 2008 31 2 205 216 10.1007/s10545-008-0841-x 2-s2.0-43149094182 18392741 · DOI
  20. [23]Davidzon G. Mancuso M. Ferraris S. POLG mutations and Alpers syndrome Annals of Neurology 2005 57 6 921 923 10.1002/ana.20498 2-s2.0-20444370205 15929042 · DOI
  21. [24]Sabbagha N. G. Kao H. J. Yang C. F. Alternative splicing in Acad8 resulting a mitochondrial defect and progressive hepatic steatosis in mice Pediatric Research 2011 70 1 31 36 10.1203/PDR.0b013e31821b89ee 2-s2.0-79960228914 21659959 · DOI
  22. [25]Ding R. B. Bao J. Deng C. X. Emerging roles of SIRT1 in fatty liver diseases International Journal of Biological Sciences 2017 13 7 852 867 10.7150/ijbs.19370 2-s2.0-85025167674 28808418 PMC5555103 · DOI
  23. [26]Li M. Guo K. Vanella L. Taketani S. Adachi Y. Ikehara S. Stem cell transplantation upregulates Sirt1 and antioxidant expression, ameliorating fatty liver in type 2 diabetic mice International Journal of Biological Sciences 2015 11 4 472 481 10.7150/ijbs.10809 2-s2.0-84928790444 25798066 PMC4366645 · DOI
  24. [28]Houtkooper R. H. Canto C. Wanders R. J. Auwerx J. The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways Endocrine Reviews 2010 31 2 194 223 10.1210/er.2009-0026 2-s2.0-77953631698 20007326 PMC2852209 · DOI · Paper page
  25. [30]Donnelly K. L. Smith C. I. Schwarzenberg S. J. Jessurun J. Boldt M. D. Parks E. J. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease The Journal of Clinical Investigation 2005 115 5 1343 1351 10.1172/JCI23621 15864352 PMC1087172 · DOI · Paper page
  26. [31]Yamaguchi K. Yang L. McCall S. Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis Hepatology 2007 45 6 1366 1374 10.1002/hep.21655 2-s2.0-34250356015 17476695 · DOI
  27. [32]Patterson R. E. Kalavalapalli S. Williams C. M. Lipotoxicity in steatohepatitis occurs despite an increase in tricarboxylic acid cycle activity American Journal of Physiology Endocrinology and Metabolism 2016 310 7 E484 E494 10.1152/ajpendo.00492.2015 2-s2.0-84969704993 26814015 PMC4824140 · DOI · Paper page
  28. [33]Kushnareva Y. Murphy A. N. Andreyev A. Complex I-mediated reactive oxygen species generation: modulation by cytochrome c and NAD(P)+ oxidation-reduction state The Biochemical Journal 2002 368 2 545 553 10.1042/BJ20021121 2-s2.0-0036903625 12180906 PMC1222999 · DOI
  29. [34]Hensley K. Kotake Y. Sang H. Dietary choline restriction causes complex I dysfunction and increased H2O2 generation in liver mitochondria Carcinogenesis 2000 21 5 983 989 10.1093/carcin/21.5.983 10783322 · DOI
  30. [35]Chalasani N. Gorski J. C. Asghar M. S. Hepatic cytochrome P450 2E1 activity in nondiabetic patients with nonalcoholic steatohepatitis Hepatology 2003 37 3 544 550 10.1053/jhep.2003.50095 2-s2.0-0037369729 12601351 · DOI
  31. [36]Weltman M. D. Farrell G. C. Liddle C. Increased hepatocyte CYP2E1 expression in a rat nutritional model of hepatic steatosis with inflammation Gastroenterology 1996 111 6 1645 1653 10.1016/S0016-5085(96)70028-8 2-s2.0-0029829455 8942745 · DOI
  32. [37]Aubert J. Begriche K. Knockaert L. Robin M. A. Fromenty B. Increased expression of cytochrome P450 2E1 in nonalcoholic fatty liver disease: mechanisms and pathophysiological role Clinics and Research in Hepatology and Gastroenterology 2011 35 10 630 637 10.1016/j.clinre.2011.04.015 2-s2.0-80054859494 21664213 · DOI
  33. [38]Varela N. M. Quinones L. A. Orellana M. Study of cytochrome P450 2E1 and its allele variants in liver injury of nondiabetic, nonalcoholic steatohepatitis obese women Biological Research 2008 41 1 81 92 10.4067/S0716-97602008000100010 18769766 · DOI
  34. [39]Caballero F. Fernandez A. Matias N. Specific contribution of methionine and choline in nutritional nonalcoholic steatohepatitis: impact on mitochondrial S-adenosyl-L-methionine and glutathione Journal of Biological Chemistry 2010 285 24 18528 18536 10.1074/jbc.M109.099333 2-s2.0-77953305752 20395294 PMC2881778 · DOI
  35. [40]Nobili V. Donati B. Panera N. A 4-polymorphism risk score predicts steatohepatitis in children with nonalcoholic fatty liver disease Journal of Pediatric Gastroenterology and Nutrition 2014 58 5 632 636 10.1097/MPG.0000000000000279 2-s2.0-84900417152 24345846 · DOI
  36. [41]Gao D. Wei C. Chen L. Huang J. Yang S. Diehl A. M. Oxidative DNA damage and DNA repair enzyme expression are inversely related in murine models of fatty liver disease American Journal of Physiology Gastrointestinal and Liver Physiology 2004 287 5 G1070 G1077 10.1152/ajpgi.00228.2004 2-s2.0-7044264899 15231485 · DOI
  37. [42]Wang D. Wei Y. Pagliassotti M. J. Saturated fatty acids promote endoplasmic reticulum stress and liver injury in rats with hepatic steatosis Endocrinology 2006 147 2 943 951 10.1210/en.2005-0570 2-s2.0-30944451788 16269465 · DOI
  38. [43]Wei Y. Wang D. Topczewski F. Pagliassotti M. J. Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells American Journal of Physiology Endocrinology and Metabolism 2006 291 2 E275 E281 10.1152/ajpendo.00644.2005 2-s2.0-33745828301 16492686 · DOI
  39. [44]Ricchi M. Odoardi M. R. Carulli L. Differential effect of oleic and palmitic acid on lipid accumulation and apoptosis in cultured hepatocytes Journal of Gastroenterology and Hepatology 2009 24 5 830 840 10.1111/j.1440-1746.2008.05733.x 2-s2.0-65949090538 19207680 · DOI
  40. [45]Feldstein A. E. Werneburg N. W. Li Z. Bronk S. F. Gores G. J. Bax inhibition protects against free fatty acid-induced lysosomal permeabilization American Journal of Physiology Gastrointestinal and Liver Physiology 2006 290 6 G1339 G1346 10.1152/ajpgi.00509.2005 2-s2.0-33646891970 16484678 PMC3056273 · DOI · Paper page
  41. [46]Leamy A. K. Egnatchik R. A. Shiota M. Enhanced synthesis of saturated phospholipids is associated with ER stress and lipotoxicity in palmitate treated hepatic cells Journal of Lipid Research 2014 55 7 1478 1488 10.1194/jlr.M050237 2-s2.0-84904015435 24859739 PMC4076085 · DOI
  42. [47]Malhotra J. D. Kaufman R. J. The endoplasmic reticulum and the unfolded protein response Seminars in Cell & Developmental Biology 2007 18 6 716 731 10.1016/j.semcdb.2007.09.003 2-s2.0-36248949141 18023214 PMC2706143 · DOI
  43. [48]Song B. Scheuner D. Ron D. Pennathur S. Kaufman R. J. Chop deletion reduces oxidative stress, improves β cell function, and promotes cell survival in multiple mouse models of diabetes The Journal of Clinical Investigation 2008 118 10 3378 3389 10.1172/JCI34587 2-s2.0-55849096988 18776938 PMC2528909 · DOI
  44. [51]Shimizu Y. Hendershot L. M. Oxidative folding: cellular strategies for dealing with the resultant equimolar production of reactive oxygen species Antioxidants & Redox Signaling 2009 11 9 2317 2331 10.1089/ARS.2009.2501 2-s2.0-68949196897 19243234 PMC2819804 · DOI
  45. [52]Rinella M. E. Siddiqui M. S. Gardikiotes K. Gottstein J. Elias M. Green R. M. Dysregulation of the unfolded protein response in db/db mice with diet-induced steatohepatitis Hepatology 2011 54 5 1600 1609 10.1002/hep.24553 2-s2.0-80055033307 21748768 PMC3205284 · DOI
  46. [54]Fuchs C. D. Claudel T. Scharnagl H. Stojakovic T. Trauner M. FXR controls CHOP expression in steatohepatitis FEBS Letters 2017 591 20 3360 3368 10.1002/1873-3468.12845 2-s2.0-85031115448 28895119 PMC5698708 · DOI
  47. [56]Deniaud A. Sharaf el dein O. Maillier E. Endoplasmic reticulum stress induces calcium-dependent permeability transition, mitochondrial outer membrane permeabilization and apoptosis Oncogene 2008 27 3 285 299 10.1038/sj.onc.1210638 2-s2.0-38049155818 17700538 · DOI · Paper page
  48. [57]Wei Y. Wang D. Gentile C. L. Pagliassotti M. J. Reduced endoplasmic reticulum luminal calcium links saturated fatty acid-mediated endoplasmic reticulum stress and cell death in liver cells Molecular and Cellular Biochemistry 2009 331 1-2 31 40 10.1007/s11010-009-0142-1 2-s2.0-74049143238 19444596 PMC2899892 · DOI
  49. [58]Fu S. Yang L. Li P. Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity Nature 2011 473 7348 528 531 10.1038/nature09968 2-s2.0-79957605136 21532591 PMC3102791 · DOI
  50. [59]Kang S. Dahl R. Hsieh W. Small molecular allosteric activator of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) attenuates diabetes and metabolic disorders Journal of Biological Chemistry 2016 291 10 5185 5198 10.1074/jbc.M115.705012 2-s2.0-84964599823 26702054 PMC4777852 · DOI
  51. [60]Greene M. W. Burrington C. M. Ruhoff M. S. Johnson A. K. Chongkrairatanakul T. Kangwanpornsiri A. PKCδ is activated in a dietary model of steatohepatitis and regulates endoplasmic reticulum stress and cell death Journal of Biological Chemistry 2010 285 53 42115 42129 10.1074/jbc.M110.168575 2-s2.0-78650649415 20971848 PMC3009937 · DOI
  52. [61]Lai S. Li Y. Kuang Y. PKCδ silencing alleviates saturated fatty acid induced ER stress by enhancing SERCA activity Bioscience Reports 2017 37 6, article BSR20170869 10.1042/BSR20170869 2-s2.0-85039838635 29046367 PMC5700272 · DOI
  53. [62]Okada K. Warabi E. Sugimoto H. Deletion of Nrf2 leads to rapid progression of steatohepatitis in mice fed atherogenic plus high-fat diet Journal of Gastroenterology 2013 48 5 620 632 10.1007/s00535-012-0659-z 2-s2.0-84878111720 22972520 · DOI
  54. [63]Bacon B. R. Farahvash M. J. Janney C. G. Neuschwander-Tetri B. A. Nonalcoholic steatohepatitis: an expanded clinical entity Gastroenterology 1994 107 4 1103 1109 7523217 10.1016/0016-5085(94)90235-6 2-s2.0-0028070562 7523217 · DOI
  55. [64]Hagstrom H. Nasr P. Bottai M. Elevated serum ferritin is associated with increased mortality in non-alcoholic fatty liver disease after 16 years of follow-up Liver International 2016 36 11 1688 1695 10.1111/liv.13144 2-s2.0-84991515493 27064133 · DOI
  56. [65]Nelson J. E. Brunt E. M. Kowdley K. V. Lower serum hepcidin and greater parenchymal iron in nonalcoholic fatty liver disease patients with C282Y HFE mutations Hepatology 2012 56 5 1730 1740 10.1002/hep.25856 2-s2.0-84868213438 22611049 PMC3462887 · DOI
  57. [66]George D. K. Goldwurm S. MacDonald G. A. Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis Gastroenterology 1998 114 2 311 318 10.1016/S0016-5085(98)70482-2 2-s2.0-0031915149 9453491 · DOI
  58. [67]Dongiovanni P. Fracanzani A. L. Fargion S. Valenti L. Iron in fatty liver and in the metabolic syndrome: a promising therapeutic target Journal of Hepatology 2011 55 4 920 932 10.1016/j.jhep.2011.05.008 2-s2.0-80052940689 21718726 · DOI
  59. [68]Valenti L. Rametta R. Dongiovanni P. The A736V TMPRSS6 polymorphism influences hepatic iron overload in nonalcoholic fatty liver disease PLoS One 2012 7 11, article e48804 10.1371/journal.pone.0048804 2-s2.0-84868349912 23144979 PMC3489825 · DOI
  60. [69]Yokota S. Oda T. Fahimi H. D. The role of 15-lipoxygenase in disruption of the peroxisomal membrane and in programmed degradation of peroxisomes in normal rat liver Journal of Histochemistry & Cytochemistry 2001 49 5 613 621 10.1177/002215540104900508 2-s2.0-0035030869 11304799 · DOI
  61. [70]Cornejo P. Varela P. Videla L. A. Fernandez V. Chronic iron overload enhances inducible nitric oxide synthase expression in rat liver Nitric Oxide 2005 13 1 54 61 10.1016/j.niox.2005.04.009 2-s2.0-20744437023 15927492 · DOI
  62. [71]Imeryuz N. Tahan V. Sonsuz A. Iron preloading aggravates nutritional steatohepatitis in rats by increasing apoptotic cell death Journal of Hepatology 2007 47 6 851 859 10.1016/j.jhep.2007.06.018 2-s2.0-35748974840 17825453 · DOI
  63. [72]Minamiyama Y. Takemura S. Kodai S. Iron restriction improves type 2 diabetes mellitus in Otsuka Long-Evans Tokushima fatty rats American Journal of Physiology Endocrinology and Metabolism 2010 298 6 E1140 E1149 10.1152/ajpendo.00620.2009 2-s2.0-77952628680 20215574 · DOI
  64. [73]Brown K. E. Dennery P. A. Ridnour L. A. Effect of iron overload and dietary fat on indices of oxidative stress and hepatic fibrogenesis in rats Liver International 2003 23 4 232 242 10.1034/j.1600-0676.2003.00832.x 12895262 · DOI
  65. [74]Malaguarnera L. Madeddu R. Palio E. Arena N. Malaguarnera M. Heme oxygenase-1 levels and oxidative stress-related parameters in non-alcoholic fatty liver disease patients Journal of Hepatology 2005 42 4 585 591 10.1016/j.jhep.2004.11.040 2-s2.0-14844288046 15763346 · DOI
  66. [75]Inoue M. Tazuma S. Kanno K. Hyogo H. Igarashi K. Chayama K. Bach1 gene ablation reduces steatohepatitis in mouse MCD diet model Journal of Clinical Biochemistry and Nutrition 2011 48 2 161 166 10.3164/jcbn.09-122GFR 2-s2.0-79952425249 21373270 PMC3045690 · DOI
  67. [76]Otogawa K. Kinoshita K. Fujii H. Erythrophagocytosis by liver macrophages (Kupffer cells) promotes oxidative stress, inflammation, and fibrosis in a rabbit model of steatohepatitis The American Journal of Pathology 2007 170 3 967 980 10.2353/ajpath.2007.060441 2-s2.0-34247844680 17322381 PMC1864892 · DOI
  68. [77]Maeda H. Yoshida K. Intermittent hypoxia upregulates hepatic heme oxygenase-1 and ferritin-1, thereby limiting hepatic pathogenesis in rats fed a high-fat diet Free Radical Research 2016 50 7 720 731 10.3109/10715762.2016.1170125 2-s2.0-84964461183 27021659 · DOI
  69. [80]Sanduzzi Zamparelli M. Compare D. Coccoli P. The metabolic role of gut microbiota in the development of nonalcoholic fatty liver disease and cardiovascular disease International Journal of Molecular Sciences 2016 17 8 10.3390/ijms17081225 2-s2.0-85016312583 27483246 PMC5000623 · DOI
  70. [81]Federico A. Dallio M. Caprio G. G. Ormando V. M. Loguercio C. Gut microbiota and the liver Minerva Gastroenterologica e Dietologica 2017 63 4 385 398 10.23736/S1121-421X.17.02375-3 2-s2.0-85030469985 28927250 · DOI
  71. [82]Betrapally N. S. Gillevet P. M. Bajaj J. S. Changes in the intestinal microbiome and alcoholic and nonalcoholic liver diseases: causes or effects? Gastroenterology 2016 150 8 1745 1755.e3 10.1053/j.gastro.2016.02.073 2-s2.0-84964263169 26948887 PMC5026236 · DOI · Paper page
  72. [84]Peterson L. W. Artis D. Intestinal epithelial cells: regulators of barrier function and immune homeostasis Nature Reviews Immunology 2014 14 3 141 153 10.1038/nri3608 2-s2.0-84896851032 24566914 · DOI
  73. [85]Rahman K. Desai C. Iyer S. S. Loss of junctional adhesion molecule a promotes severe steatohepatitis in mice on a diet high in saturated fat, fructose, and cholesterol Gastroenterology 2016 151 4 733 746.e12 10.1053/j.gastro.2016.06.022 2-s2.0-84989859198 27342212 PMC5037035 · DOI
  74. [86]Guo H. Callaway J. B. Ting J. P. Inflammasomes: mechanism of action, role in disease, and therapeutics Nature Medicine 2015 21 7 677 687 10.1038/nm.3893 2-s2.0-84936891896 26121197 PMC4519035 · DOI · Paper page
  75. [89]Zaki M. H. Boyd K. L. Vogel P. Kastan M. B. Lamkanfi M. Kanneganti T. D. The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis Immunity 2010 32 3 379 391 10.1016/j.immuni.2010.03.003 2-s2.0-77950002937 20303296 PMC2982187 · DOI · Paper page
  76. [90]Elinav E. Strowig T. Kau A. L. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis Cell 2011 145 5 745 757 10.1016/j.cell.2011.04.022 2-s2.0-79957576718 21565393 PMC3140910 · DOI · Paper page
  77. [91]De Minicis S. Rychlicki C. Agostinelli L. Dysbiosis contributes to fibrogenesis in the course of chronic liver injury in mice Hepatology 2014 59 5 1738 1749 10.1002/hep.26695 2-s2.0-84899474318 23959503 · DOI · Paper page
  78. [94]de Medeiros I. C. de Lima J. G. Is nonalcoholic fatty liver disease an endogenous alcoholic fatty liver disease?—A mechanistic hypothesis Medical Hypotheses 2015 85 2 148 152 10.1016/j.mehy.2015.04.021 2-s2.0-84944358185 25956735 · DOI
  79. [95]Woodhouse C. A. Patel V. C. Singanayagam A. Shawcross D. L. Review article: the gut microbiome as a therapeutic target in the pathogenesis and treatment of chronic liver disease Alimentary Pharmacology and Therapeutics 2018 47 2 192 202 10.1111/apt.14397 2-s2.0-85032741399 29083037 · DOI
  80. [96]Pasarin M. La Mura V. Gracia-Sancho J. Sinusoidal endothelial dysfunction precedes inflammation and fibrosis in a model of NAFLD PLoS One 2012 7 4, article e32785 10.1371/journal.pone.0032785 2-s2.0-84859238635 22509248 PMC3317918 · DOI
  81. [97]Yoon Y. Song J. Hong S. H. Kim J. Q. Plasma nitric oxide concentrations and nitric oxide synthase gene polymorphisms in coronary artery disease Clinical Chemistry 2000 46 10 1626 1630 11017941
  82. [98]Potenza M. A. Marasciulo F. L. Chieppa D. M. Insulin resistance in spontaneously hypertensive rats is associated with endothelial dysfunction characterized by imbalance between NO and ET-1 production American Journal of Physiology Heart and Circulatory Physiology 2005 289 2 H813 H822 10.1152/ajpheart.00092.2005 2-s2.0-23744511665 15792994 · DOI · Paper page
  83. [99]Perreault M. Marette A. Targeted disruption of inducible nitric oxide synthase protects against obesity-linked insulin resistance in muscle Nature Medicine 2001 7 10 1138 1143 10.1038/nm1001-1138 2-s2.0-0034770292 11590438 · DOI
  84. [101]Dallaire P. Bellmann K. Laplante M. Obese mice lacking inducible nitric oxide synthase are sensitized to the metabolic actions of peroxisome proliferator–activated receptor-γ agonism Diabetes 2008 57 8 1999 2011 10.2337/db08-0540 2-s2.0-50949133177 18458147 PMC2494686 · DOI
  85. [102]Langer D. A. Das A. Semela D. Nitric oxide promotes caspase-independent hepatic stellate cell apoptosis through the generation of reactive oxygen species Hepatology 2008 47 6 1983 1993 10.1002/hep.22285 2-s2.0-46249116797 18459124 PMC2562502 · DOI
  86. [103]Iwakiri Y. Grisham M. Shah V. Vascular biology and pathobiology of the liver: report of a single-topic symposium Hepatology 2008 47 5 1754 1763 10.1002/hep.22203 2-s2.0-43949084424 18393322 PMC2724750 · DOI
  87. [104]Gonzalez-Paredes F. J. Hernandez Mesa G. Morales Arraez D. Contribution of cyclooxygenase end products and oxidative stress to intrahepatic endothelial dysfunction in early non-alcoholic fatty liver disease PLoS One 2016 11 5, article e0156650 10.1371/journal.pone.0156650 2-s2.0-84971254694 27227672 PMC4882009 · DOI
  88. [106]Couillard C. Ruel G. Archer W. R. Circulating levels of oxidative stress markers and endothelial adhesion molecules in men with abdominal obesity The Journal of Clinical Endocrinology & Metabolism 2005 90 12 6454 6459 10.1210/jc.2004-2438 2-s2.0-28744458485 16189262 · DOI
  89. [107]Furukawa S. Fujita T. Shimabukuro M. Increased oxidative stress in obesity and its impact on metabolic syndrome The Journal of Clinical Investigation 2004 114 12 1752 1761 10.1172/JCI21625 15599400 PMC535065 · DOI · Paper page
  90. [109]Grattagliano I. Palmieri V. O. Portincasa P. Moschetta A. Palasciano G. Oxidative stress-induced risk factors associated with the metabolic syndrome: a unifying hypothesis The Journal of Nutritional Biochemistry 2008 19 8 491 504 10.1016/j.jnutbio.2007.06.011 2-s2.0-46749149676 17855068 · DOI
  91. [110]Palmieri V. O. Grattagliano I. Portincasa P. Palasciano G. Systemic oxidative alterations are associated with visceral adiposity and liver steatosis in patients with metabolic syndrome The Journal of Nutrition 2006 136 12 3022 3026 10.1093/jn/136.12.3022 17116714 · DOI · Paper page
  92. [111]Stiuso P. Scognamiglio I. Murolo M. Serum oxidative stress markers and lipidomic profile to detect NASH patients responsive to an antioxidant treatment: a pilot study Oxidative Medicine and Cellular Longevity 2014 2014 8 169216 10.1155/2014/169216 2-s2.0-84903592183 24987492 PMC4060161 · DOI
  93. [112]Suthanthiran M. Anderson M. E. Sharma V. K. Meister A. Glutathione regulates activation-dependent DNA synthesis in highly purified normal human T lymphocytes stimulated via the CD2 and CD3 antigens Proceedings of the National Academy of Sciences of the United States of America 1990 87 9 3343 3347 10.1073/pnas.87.9.3343 2-s2.0-0025312043 1970635 PMC53896 · DOI
  94. [113]Chalasani N. Deeg M. A. Crabb D. W. Systemic levels of lipid peroxidation and its metabolic and dietary correlates in patients with nonalcoholic steatohepatitis The American Journal of Gastroenterology 2004 99 8 1497 1502 10.1111/j.1572-0241.2004.30159.x 2-s2.0-4444382031 15307867 · DOI · Paper page
  95. [114]Donati G. Stagni B. Piscaglia F. Increased prevalence of fatty liver in arterial hypertensive patients with normal liver enzymes: role of insulin resistance Gut 2004 53 7 1020 1023 10.1136/gut.2003.027086 2-s2.0-3042521502 15194655 PMC1774102 · DOI
  96. [115]Diehl A. M. Fatty liver, hypertension, and the metabolic syndrome Gut 2004 53 7 923 924 10.1136/gut.2003.037309 2-s2.0-3042628302 15194635 PMC1774127 · DOI
  97. [116]Gholam P. M. Flancbaum L. Machan J. T. Charney D. A. Kotler D. P. Nonalcoholic fatty liver disease in severely obese subjects The American Journal of Gastroenterology 2007 102 2 399 408 10.1111/j.1572-0241.2006.01041.x 2-s2.0-33846473612 17311652 · DOI
  98. [118]Persico M. Masarone M. Damato A. Non alcoholic fatty liver disease and eNOS dysfunction in humans BMC Gastroenterology 2017 17 1 p. 35 10.1186/s12876-017-0592-y 2-s2.0-85014615399 28264657 PMC5340006 · DOI

Cited by

Sorted by citations

Authors
Masarone, M., Rosato, V., Dallio, M., Gravina, A. G., Aglitti, A., Loguercio, C., Federico, A., & Persico, M.
Affiliations
  • University of Salerno (IT)
  • University of Campania "Luigi Vanvitelli" (IT)
Corresponding author
Masarone, Mario
ORCID
Venue
Oxidative Medicine and Cellular Longevity
Publisher
Wiley
Published
2018-01
Volume
2018
Issue
1
Pages
9547613-9547613
ISSN
  • 1942-0994 (ISSN-L)
  • 1942-0900
DOI
10.1155/2018/9547613
PMC
PMC6016172
OpenAlex
W2807938853
Cited by
648
References
20
Citations by year
2026: 33 · 2025: 60 · 2024: 71 · 2023: 96 · 2022: 99 · 2021: 133 · 2020: 99 · 2019: 47 · 2018: 10
FWCI
10.32
Type
journal article
Language
en
Update notices
correction (2021-07-31)
Open access
Licence
Locations
  • Oxidative Medicine and Cellular Longevity (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords
non-alcoholic fatty liver disease, oxidative stress, hepatic steatosis, nonalcoholic steatohepatitis, liver fibrosis, liver cirrhosis, hepatocellular carcinoma, pathogenesis, liver inflammation
MeSH terms
Animals, Carcinoma, Hepatocellular, Humans, Liver, Liver Cirrhosis, Oxidative Stress, Non-alcoholic Fatty Liver Disease

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review