Cited by 250Liver Disease Diagnosis and TreatmentAlcohol Consumption and Health EffectsLiver physiology and pathology

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Nonalcoholic Fatty Liver Disease: Pathogenesis and the Role of Antioxidants

Mehta, Kapil, Van Thiel, David H., Shah, Nikunj, Mobarhan, Sohrab·2002·Nutrition Reviews

DOI 10.1301/002966402320387224

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Abstract

Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of liver injury ranging from simple steatosis to steatohepatitis, fibrosis, and cirrhosis. Whereas simple steatosis has a benign clinical course, steatohepatitis is a recognized cause of progressive liver fibrosis and can develop into cirrhosis. NAFLD and nonalcoholic steatohepatitis (NASH) are the two most common chronic liver diseases in United States general population with a prevalence of 20% and 3%, respectively. Hepatic steatosis is frequently associated with obesity, type 2 diabetes, and hyperlipidemia with insulin resistance as a key pathogenic factor. A two-hit theory best describes the progression from simple steatosis to NASH, fibrosis, or cirrhosis. These two hits consist of the accumulation of excessive hepatic fat primarily owing to insulin resistance, and oxidative stress owing to reactive oxygen species (ROS). Mitochondria are the major cellular source of ROS in cases of NASH. Currently, treatment is focused on modifying risk factors such as obesity, diabetes mellitus, and hyperlipidemia. Antioxidants such as vitamin E, N-acetylcysteine, betaine, and others may be beneficial in the treatment of NASH.

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Abiru, S., Migita, K., Maeda, Y., Daikoku, M., Ito, M., Ohata, K., Nagaoka, S., Matsumoto, T., Takii, Y., Kusumoto, K., et al. (2005) · Liver International · doi:10.1111/j.1478-3231.2005.01191.x · Cited by 209
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Background
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BackgroundInfluential
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“inducing vicious cycles of oxidative injury leading to inflammation and fibrosis [46].”
Background
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Baumgardner, J. N., Shankar, K., Hennings, L. J., Albano, E., Badger, T. M., & Ronis, M. J. J. (2008) · Journal of Nutrition · doi:10.1093/jn/138.10.1872 · Cited by 100
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Jiang, T., Xiao, Y., Zhou, J., Luo, Z., Yu, L., Liao, Q., Liu, S., Qi, X., Zhang, H., Hou, M., et al. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102963 · Cited by 101
“The second hit involves oxidative stress [23].”
Non-alcoholic steatohepatitis: review of a growing medical problem
Sligte, K. T., Bourass, I., Sels, J.-P. J. E., Driessen, A. L. C., Stockbrügger, R. W., & Koek, G. H. (2004) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2003.12.008 · Cited by 95
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Background
Lipotoxicity in HepG2 cells triggered by free fatty acids.
(2011) · PubMed Central · Cited by 94
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de Oliveira, C. P. M. S., Coelho, A. M. M., Barbeiro, H. V., de Lima, V. M. R., Soriano, F. G., RIBEIRO, C. F. D. S., Molan, N. A., Alves, V. A. F., de Souza, H. P., Machado, M. C. C., et al. (2006) · Brazilian Journal of Medical and Biological Research · doi:10.1590/s0100-879x2006000200004 · Cited by 94
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Background
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Fiorini, R. N., Donovan, J. L., Rodwell, D., Evans, Z. P., Cheng, G., May, H. D., Milliken, C. E., Markowitz, J. S., Campbell, C., Haines, J. K., et al. (2005) · Liver Transplantation · doi:10.1002/lt.20348 · Cited by 91
Non-Alcoholic Fatty Liver Disease in Young Adult Severely Obese Non-Diabetic Patients in South Italy
Colicchio, P., Tarantino, G., del Genio, F., et al. (2005) · Annals of Nutrition and Metabolism · doi:10.1159/000087295 · Cited by 90
“Hyperinsulinemia in fact contributes to liver steatosis depressing mitochondrial beta-oxidation of fatty acids in the liver by diverting acyl-CoA to triglyceride (TG) synthesis; it also inhibits hepatic TG secretion, whilst, in presence of excess body fat, free fatty acids (FFA) flux to the liver remains unchanged [ ,”
Background
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Wang, Y., Zhou, M., Lam, K. S. L., & Xu, A. (2009) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302009000200012 · Cited by 90
The Osmolyte Strategy of Normal Human Keratinocytes in Maintaining Cell Homeostasis
Warskulat, U., Reinen, A., Grether‐Beck, S., Krutmann, J., & Häussinger, D. (2004) · Journal of Investigative Dermatology · doi:10.1111/j.0022-202x.2004.23313.x · Cited by 85
The role of the nuclear receptor constitutive androstane receptor in the pathogenesis of non-alcoholic steatohepatitis
Yamazaki, Y., Kakizaki, S., Horiguchi, N., Sohara, N., Sato, K., Takagi, H., Mori, M., & Negishi, M. (2006) · Gut · doi:10.1136/gut.2006.093260 · Cited by 87
Metabolic phenotype and adipose and liver features in a high-fat Western diet-induced mouse model of obesity-linked NAFLD
Luo, Y., Burrington, C. M., Graff, E. C., Zhang, J., Judd, R. L., Suksaranjit, P., Kaewpoowat, Q., Davenport, S. K., O’Neill, A. M., & Greene, M. W. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00319.2015 · Cited by 86
The DNA damage checkpoint protein ATM promotes hepatocellular apoptosis and fibrosis in a mouse model of non-alcoholic fatty liver disease
Daugherity, E. K., Balmus, G., Saei, A. A., Moore, E. S., Abdallah, D. S. A., Rogers, A. B., Weiss, R. S., & Maurer, K. J. (2012) · Cell Cycle · doi:10.4161/cc.20259 · Cited by 84
“currently are not well understood [3,6,8,9].”
Increased lipid peroxidation in patients with non‐alcoholic fatty liver disease and chronic hepatitis C as measured by the plasma level of 8‐isoprostane
Konishi, M., Iwasa, M., Araki, J., Kobayashi, Y., Katsuki, A., Sumida, Y., Nakagawa, N., Kojima, Y., Watanabe, S., Adachi, Y., et al. (2006) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2006.04420.x · Cited by 82
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Yan, J., Jiang, J., He, L., & Chen, L. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.02.029 · Cited by 78
A review of iron studies in overweight and obese children and adolescents: a double burden in the young?
Hutchinson, C. (2016) · European Journal of Nutrition · doi:10.1007/s00394-016-1155-7 · Cited by 78
“One of the aforementioned studies, conducted in Turkey, included OB children with liver disease [45] which itself is associated with raised markers of inflammation [98, 99].”
Result
Association of Apolipoprotein E Polymorphisms in Patients with Non-Alcoholic Steatohepatitis
Sazcı, A., Akpınar, G., Aygün, C., Ergül, E., Şentürk, Ö., & Hülagü, S. (2008) · Digestive Diseases and Sciences · doi:10.1007/s10620-008-0271-5 · Cited by 77
“Although the mechanism for the pathogenesis of NASH remains poorly understood, hepatic fatty acid infiltration has been proposed to stem from the continuous delivery of free fatty acids into the liver after the ingestion of fatty foods and from increased splanchnic lipolysis of visceral fat, both of which increase hep…”
Background
Effects of vitamin E treatment on peroxisome proliferator‐activated receptor‐α expression and insulin resistance in patients with non‐alcoholic steatohepatitis: results of a pilot study
Yakaryılmaz, F., Güliter, S., Savaş, B., Erdem, Ö., Ersoy, R., Erden, E., Akyol, G., Bozkaya, H., & Özeni̇rler, S. (2007) · Internal Medicine Journal · doi:10.1111/j.1445-5994.2006.01295.x · Cited by 75
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Xia, S., Le, G., Wang, P., Qiu, Y., Jiang, Y., & Xue Ming, T. A. N. G. (2016) · Nutrients · doi:10.3390/nu8120799 · Cited by 76
“Hepatic steatosis, the “first hit” of NAFLD, is characteriz d by fat infiltr tion and excessive lipid accumulation in the liver, accompanied by an elevated liver/body ratio and higher plasma levels of enzyme markers of liver damage.”
BackgroundInfluential
Glutathione‐enhancing agents protect against steatohepatitis in a dietary model
Oz, H. S., Im, H., Chen, T. S., et al. (2006) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.20109 · Cited by 74
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Morita, M., Ishida, N., Uchiyama, K., Yamaguchi, K., Itoh, Y., Shichiri, M., Yoshida, Y., Hagihara, Y., Naito, Y., Yoshikawa, T., et al. (2012) · Free Radical Research · doi:10.3109/10715762.2012.677840 · Cited by 73
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Collins, P., Jones, C., Choudhury, S., Damelin, L. H., & Hodgson, H. J. F. (2005) · Liver International · doi:10.1111/j.1478-3231.2005.01104.x · Cited by 74
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“, oxidative stress/ lipid peroxidation, and tumor necrosis factor α (TNFα)/endotoxinmediated injury [17].”
Background
Antioxidant effects of the chestnut (Castanea crenata) inner shell extract in t-BHP-treated HepG2 cells, and CCl4- and high-fat diet-treated mice
Noh, J., Gang, G., Kim, Y.-H., Yang, K.-J., Hwang, J., Lee, H.-S., Oh, W. K., Song, K., & Lee, C. (2010) · Food and Chemical Toxicology · doi:10.1016/j.fct.2010.08.018 · Cited by 69
“Previous studies have demonstrated that HFD leads to liver injury and insulin resistance through oxidative stress (Borst and Conover, 2005; Mehta et al., 2002), and the increased generation of ROS may cause lipid peroxidation followed by an inflammatory response, and may even activate stellate cells and lead to fibros…”
Background
Mitochondrial Uncoupling Protein-2 Mediates Steatotic Liver Injury following Ischemia/Reperfusion
Evans, Z. P., Ellett, J. D., Schmidt, M. G., Schnellmann, R. G., & Chavin, K. D. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m706784200 · Cited by 69
The antioxidant and antifibrogenic effects of the glycosaminoglycans hyaluronic acid and chondroitin-4-sulphate in a subchronic rat model of carbon tetrachloride-induced liver fibrogenesis
Campo, G. M., Avenoso, A., Campo, S., D’Ascola, A., Ferlazzo, A. M., & Calatroni, A. (2004) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2004.05.004 · Cited by 65
Astaxanthin and Corni Fructus Protect Against Diabetes-Induced Oxidative Stress, Inflammation, and Advanced Glycation End Product in Livers of Streptozotocin-Induced Diabetic Rats
Park, C. H., Xu, F. H., Roh, S., Song, Y. O., UEBABA, K., Noh, J. S., & Yokozawa, T. (2015) · Journal of Medicinal Food · doi:10.1089/jmf.2014.3174 · Cited by 63
“Clinical studies also reported that hyperglycemia enhances the pathogenicity of liver disease through increasing oxidative stress.(29,30) Patients with diabetes FIG.”
Randomized Clinical Trial: Bergamot Citrus and Wild Cardoon Reduce Liver Steatosis and Body Weight in Non-diabetic Individuals Aged Over 50 Years
Ferro, Y., Montalcini, T., Mazza, E., FOTI, D. P., Angotti, E., Gliozzi, M., Nucera, S., Paone, S., Bombardelli, E., Aversa, I., et al. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00494 · Cited by 62
“Additional factors involved in the pathogenesis of NAFLD are obesity and obesity-relatedmetabolic disorders (6, 7).”
Background
The effects of L-tryptophan and melatonin on selected biochemical parameters in patients with steatohepatitis.
Cichoż‐Lach, H., Celiński, K., Konturek, P. C., Konturek, S. J., & Słomka, M. (2010) · PubMed · Cited by 62
Attenuation of Fatty Liver and Prevention of Hypercholesterolemia by Extract of Curcuma longa through Regulating the Expression of CYP7A1, LDL‐Receptor, HO‐1, and HMG‐CoA Reductase
Yiu, W. C., Kwan, P.-L., Wong, C., Kam, T., Chiu, S., Chan, S., & Chan, R. Y. (2011) · Journal of Food Science · doi:10.1111/j.1750-3841.2011.02042.x · Cited by 62
Impaired Autophagic Clearance After Cold Preservation of Fatty Livers Correlates with Tissue Necrosis Upon Reperfusion and Is Reversed by Hypothermic Reconditioning
Minor, T., Stegemann, J., Hirner, A., et al. (2009) · Liver Transplantation · doi:10.1002/lt.21751 · Cited by 60
“Increased oxidative stress(9) has also been reported to promote higher postischemic dysfunction rates in steatotic livers, and mitochondria appear to be a prominent cellular source of reactive oxygen species.(10) Actually, fatty livers show a greater mitochondrial content of oxidized lipids and proteins than normal li…”
Background
Therapeutic Strategies for Mitochondrial Dysfunction and Oxidative Stress in Age-Related Metabolic Disorders
Bhatti, J. S., Kumar, S., Vijayan, M., Bhatti, G. K., & Reddy, P. H. (2017) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2016.12.012 · Cited by 61
Association between thrombotic risk factors and extent of fibrosis in patients with non-alcoholic fatty liver diseases
Assy, N. (2005) · World Journal of Gastroenterology · doi:10.3748/wjg.v11.i37.5834 · Cited by 60
“Recently, two additional mechanisms were reported: oxidative stress/lipid peroxidation; and TNF-α/ endotoxin-mediated injuries[ 7 ].”
Background
Melatonin ameliorates methionine‐ and choline‐deficient diet‐induced nonalcoholic steatohepatitis in rats
Tahan, V., Atuğ, Ö., Akın, H., et al. (2009) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2009.00676.x · Cited by 58
The effect of high-fat diet-induced obesity on cardiovascular toxicity in wistar albino rats
Bhandari, U., Kumar, V., Khanna, N., & Panda, B. P. (2010) · Human & Experimental Toxicology · doi:10.1177/0960327110389499 · Cited by 63
Protective Effect of Clove Oil and Eugenol Microemulsions on Fatty Liver and Dyslipidemia as Components of Metabolic Syndrome
Al‐Okbi, S. Y., Mohamed, D. A., Hamed, T. E.-S., & Edris, A. E. (2014) · Journal of Medicinal Food · doi:10.1089/jmf.2013.0033 · Cited by 58
“17,18 With the advent of nanotechnology, it was possible to fabricate bioactive compounds with unique biological properties in the form of nanoparticles (diameter r 100.0 nm).”
Influential
Intracellular Calreticulin Regulates Multiple Steps in Fibrillar Collagen Expression, Trafficking, and Processing into the Extracellular Matrix
Graham, L. V. D., Sweetwyne, M. T., Pallero, M. A., & Murphy-Ullrich, J. E. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.006841 · Cited by 56
Subcutaneous vitamin E ameliorates liver injury in an in vivo model of steatocholestasis†‡
Soden, J. S., Devereaux, M. W., Haas, J. E., Gumpricht, E., Dahl, R., Gralla, J., Traber, M. G., & Sokol, R. J. (2007) · Hepatology · doi:10.1002/hep.21690 · Cited by 53
“5 (3-4) 3 (3-4) 3 (1-4) 1 (1-2) Obese-vit E GCDC 9 7 (6-9) 2 (1-3) 2 (2-3) 2 (1-2) 1 (1-2) Lean-veh GCDC 5 9 (7-11) 2 (2-4) 3 (1-3) 3 (3-4) 1 (1) Obese-veh control 6 5.”
Lipid based nanocarriers for effective drug delivery and treatment of diabetes associated liver fibrosis
Salunkhe, S. A., Chitkara, D., Mahato, R. I., & Mittal, A. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.04.003 · Cited by 55
SARM1 deletion restrains NAFLD induced by high fat diet (HFD) through reducing inflammation, oxidative stress and lipid accumulation
Pan, Z.-G., & An, X.-S. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.02.115 · Cited by 50
Germinated brown rice ameliorates obesity in high-fat diet induced obese rats
Lim, S. M., Goh, Y. M., Mohtarrudin, N., et al. (2016) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-016-1116-y · Cited by 51
“Steatosis, the hallmark of a feature of the nonalcoholic fatty liver disease, progresses to steatohepatitis, eventually to cirrhosis [47].”
Background
Identification of liver proteins altered by type 2 diabetes mellitus in obese subjects
Valle, A., Catalán, V., Rodrı́guez, A., Rotellar, F., Valentí, V., Silva, C., Salvador, J., Frühbeck, G., Gómez‐Ambrosi, J., Roca, P., et al. (2012) · Liver International · doi:10.1111/j.1478-3231.2012.02765.x · Cited by 49
“Given that oxidative stress has been associated to diabetes (26, 27), we decided to assess oxidative stress status by measurement of glutathione levels and markers of oxidative damage.”
Evaluation of antiobesity and cardioprotective effect of Gymnema sylvestre extract in murine model
Bhandari, U., Kumar, V., Tripathi, C., & Khanna, G. (2012) · Indian Journal of Pharmacology · doi:10.4103/0253-7613.100387 · Cited by 49
Inhibition of liver X receptor-α-dependent hepatic steatosis by isoliquiritigenin, a licorice antioxidant flavonoid, as mediated by JNK1 inhibition
Kim, Y. M., Kim, T. H., Kim, Y. W., Yang, Y. M., Ryu, D. H., Hwang, S. J., Lee, J. R., Kim, S. C., & Kim, S. G. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.09.001 · Cited by 49
Lipid Peroxidation in Bariatric Candidates with Nonalcoholic Fatty Liver Disease (NAFLD) – Preliminary Findings
de Oliveira, C. P. M. S., Faintuch, J., Rascovski, A., Junior, C. K. F., Bastos, M. D. S. C. B. D. O., Matsuda, M., Nina, B. I. D., Yahnosi, K., Abdalla, D. S. P., Paranaguá‐Vezozzo, D. C., et al. (2005) · Obesity Surgery · doi:10.1381/0960892053723493 · Cited by 47
Treatment with silybin‐vitamin E‐phospholipid complex in patients with hepatitis C infection
Falasca, K., Ucciferri, C., Mancino, P., Vitacolonna, E., Tullio, D. D., Pizzigallo, E., Conti, P., & Vecchiet, J. (2008) · Journal of Medical Virology · doi:10.1002/jmv.21292 · Cited by 45
“The SPV complex has proved able to modulate HSC activation in vitro and this results in a significant reduction of collagen deposition and synthesis [Mehta et al., 2002].”
Background
Interstrain differences in susceptibility to non‐alcoholic steatohepatitis
Yamazaki, Y., Kakizaki, S., Takizawa, D., Ichikawa, T., Sato, K., Takagi, H., & Mori, M. (2007) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2007.05150.x · Cited by 46
Research on the protection effect of pioglitazone for non-alcoholic fatty liver disease (NAFLD) in rats
Xu, P., Zhang, X., Li, Y., Yu, C., Xu, L., & Xu, G.-Y. (2006) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.2006.b0627 · Cited by 46
“Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease in clinic, and has a spectrum ranging from that of fatty liver alone, usually a benign and non-progressive condition, to nonalcoholic steatohepatitis (NASH), which may progress to liver cirrhosis (Poonawala et al., 2000; Mehta et al., 2002; Bu…”
Background
Effect of Phyllanthus emblica L. fruit on methionine and choline-deficiency diet-induced nonalcoholic steatohepatitis
Tung, Y., Huang, C.-Z., Lin, J.-H., et al. (2018) · Journal of Food and Drug Analysis · doi:10.1016/j.jfda.2017.12.005 · Cited by 45
“[3] Mehta K, Van Thiel DH, Shah N, Mobarhan S.”
Background
Inhibitory effect of Nymphaea pubescens Willd. flower extract on carrageenan-induced inflammation and CCl4-induced hepatotoxicity in rats
Debnath, S., Ghosh, S., & Hazra, B. (2013) · Food and Chemical Toxicology · doi:10.1016/j.fct.2013.06.036 · Cited by 43
Antioxidant Activity of Urtica dioica: An Important Property Contributing to Multiple Biological Activities
Jaiswal, V. K., & Lee, H. (2022) · Antioxidants · doi:10.3390/antiox11122494 · Cited by 41
“Therefore, antioxidants that are used against these diseases were found to be effective [25,26].”
Background
Novel role of TLR4 in NAFLD development: Modulation of metabolic enzymes expression
Ferreira, D. F., Fiamoncini, J., Prist, I. H., Ariga, S. K., de Souza, H. P., & de Lima, T. M. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2015.07.002 · Cited by 40
“In fact, IL-6 and TNF-α production by hepatocytes are considered to be important to the initiation phase of liver regeneration [32, 33] and to the regulation of acute-phase protein and nitric oxide production triggered by LPS [34].”
Background
The role of oxidative stress in alterations of hematological parameters and inflammatory markers induced by early hypercholesterolemia
Karbiner, M. S., Sierra, L., Minahk, C. J., et al. (2013) · Life Sciences · doi:10.1016/j.lfs.2013.08.003 · Cited by 39
Beneficial effects of hydro-alcoholic extract of Caralluma fimbriata against high-fat diet-induced insulin resistance and oxidative stress in Wistar male rats
Sudhakara, G., Mallaiah, P., Sreenivasulu, N., Rao, B. S. B., Rajendran, R., & Saralakumari, D. (2014) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-013-0304-1 · Cited by 39
Molecular Mechanisms Underlying Hepatocellular Carcinoma Induction by Aberrant NRF2 Activation-Mediated Transcription Networks: Interaction of NRF2-KEAP1 Controls the Fate of Hepatocarcinogenesis
Haque, E., Karim, M. R., Teeli, A. S., Śmiech, M., Leszczyński, P., Winiarczyk, D., Parvanov, E. D., Atanasov, A. G., & Taniguchi, H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21155378 · Cited by 40
“In this regard, the disruption of lipid metabolism and oxidative stress have been reported as the main causes of NAFLD, and NRF2 is related to lipid homeostasis [118,119].”
Background
Medical Treatment of Non-alcoholic Steatohepatitis
Kadayıfçı, A., Merriman, R. B., & Bass, N. M. (2007) · Clinics in Liver Disease · doi:10.1016/j.cld.2007.02.001 · Cited by 38
Effect of Lipopolysaccharide on the Progression of Non‐Alcoholic Fatty Liver Disease in High Caloric Diet‐Fed Mice
Matsushita, N., Osaka, T., Haruta, I., Ueshiba, H., Yanagisawa, N., Omori‐Miyake, M., Hashimoto, E., Shibata, N., Tokushige, K., Saito, K., et al. (2015) · Scandinavian Journal of Immunology · doi:10.1111/sji.12397 · Cited by 38
Targeting Mitochondria as Therapeutic Strategy for Metabolic Disorders
Sorriento, D., Pascale, A. V., Finelli, R., Carillo, A. L., Annunziata, R., Trimarco, B., & Iaccarino, G. (2014) · The Scientific World JOURNAL · doi:10.1155/2014/604685 · Cited by 39
“Various vitamins and chemical compounds with antioxidant properties have been developed, including coenzymeQ [120], vitamin E [121], a-lipoic acid [122], N-acetylcysteine (NAC) [123], vitamin C, and inducers of heme oxygenase [124], which are able to reduce ROS production.”
Background
Retracted
Serum hepcidin levels and iron metabolism in obese children with and without fatty liver: case–control study
Demircioğlu, F., Görünmez, G., Dağıstan, E., Göksügür, S. B., Bekdaş, M., Tosun, M., Kızıldağ, B., & Kısmet, E. (2014) · European Journal of Pediatrics · doi:10.1007/s00431-014-2268-8 · Cited by 39
“There is evidence that systemic inflammatory response related to cytokine release is more evident in obese population with NAFLD than those without NAFLD [14].”
Background

Authors: Mehta, K., Van Thiel, D. H., Shah, N., & Mobarhan, S.
Affiliations: Loyola University Medical Center (US)
Drs. Mehta, VanThiel, Shah, and Mobarhan arewith the Division of Gastroenterology, Hepatology, and Nutrition, Loyola University Medical Center, 2160 South First Avenue, Maywood, Illinois 60153, USA.
ORCID: Shah, Nikunj
Venue: Nutrition Reviews
Publisher: Oxford University Press (OUP)
Published: 2002-09-01
Volume: 60
Issue: 9
Pages: 289-293
ISSN: 0029-6643 (ISSN-L)
1753-4887
DOI: 10.1301/002966402320387224
OpenAlex: W2123856468
Cited by: 250
References: 0
Citations by year: 2026: 1 · 2025: 7 · 2024: 5 · 2023: 7 · 2022: 7 · 2021: 4 · 2020: 6 · 2019: 8 · 2018: 11 · 2017: 7 · 2016: 18 · 2015: 16 · 2014: 20 · 2013: 12 · 2012: 8
FWCI: 7.54
Type: journal article
Language: en
Open access: closed
Locations: Nutrition Reviews (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords: non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, hepatic steatosis, liver fibrosis, liver cirrhosis, insulin resistance, two-hit theory, oxidative stress, reactive oxygen species, mitochondrial reactive oxygen species, antioxidants, vitamin E, N-acetylcysteine, betaine, obesity, type 2 diabetes, hyperlipidemia
MeSH terms: Antioxidants, Fatty Liver, Humans

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Nonalcoholic Fatty Liver Disease: Pathogenesis and the Role of Antioxidants

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