Nonalcoholic Fatty Liver Disease: Pathogenesis and the Role of Antioxidants
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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NAC counters ROS in nonalcoholic steatohepatitis, a disorder often associated with type 2 diabetes and characterized by mitochondrial ROS production.
“NAC counters ROS in nonalcoholic steatohepatitis, a disorder often associated with type 2 diabetes and characterized by mitochondrial ROS production (214).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [214]
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Bhatti, J. S., Bhatti, G. K., & Reddy, P. H. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.11.010 · Cited by 1,655 · see citing works
Craig, S. A. (2004) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/80.3.539 · Cited by 1,062 · see citing works
“One manifestation, hepatic steatosis (fatty liver), is a common result of obesity, consumption of a high-fat diet, insulin resistance, diabetes, alcohol consumption, and other liver damage (128).”
BackgroundSivitz, W. I., & Yorek, M. A. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2531 · Cited by 742 · see citing works
“NAC counters ROS in nonalcoholic steatohepatitis, a disorder often associated with type 2 diabetes and characterized by mitochondrial ROS production (214).”
The Essential Element Manganese, Oxidative Stress, and Metabolic Diseases: Links and Interactions
Li, L., & Yang, X. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/7580707 · Cited by 661 · see citing works
Roskams, T., Yang, S. Q., Koteish, A., Durnez, A., DeVos, R., Huang, X., Achten, R., Verslype, C., & Diehl, A. M. (2003) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63489-x · Cited by 447 · see citing works
“13,14 The replicative activity of mature hepatocytes is also known to be inhibited in patients with alcoholic hepatitis, 15 rodents with alcohol-induced fatty livers, 16 and in some animal models of NAFLD.”
BackgroundMantena, S. K., King, A. L., Andringa, K. K., Eccleston, H. B., & Bailey, S. M. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.12.029 · Cited by 429 · see citing works
“population is reaching 20%, with the more severe form, NASH, present in 3% [7,8].”
BackgroundRedox mechanisms in hepatic chronic wound healing and fibrogenesis
Novo, E., & Parola, M. (2008) · Fibrogenesis & Tissue Repair · doi:10.1186/1755-1536-1-5 · Cited by 406 · see citing works
Diagnosis and Therapy of Nonalcoholic Steatohepatitis
Torres, D. M., & Harrison, S. A. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.02.077 · Cited by 354 · see citing works
Progenitor Cells in Diseased Human Liver
Roskams, T., Libbrecht, L. J., & Desmet, V. J. (2003) · Seminars in Liver Disease · doi:10.1055/s-2004-815564 · Cited by 337 · see citing works
The role of oxidative stress in non-alcoholic steatohepatitis
Koek, G. H., Liedorp, P. R., & Bast, A. (2011) · Clinica Chimica Acta · doi:10.1016/j.cca.2011.04.013 · Cited by 315 · see citing works
Hepatic steatosis in obese patients: clinical aspects and prognostic significance
Festi, D., Colecchia, A., Sacco, T., Bondi, M., Roda, E., & Marchesini, G. (2004) · Obesity Reviews · doi:10.1111/j.1467-789x.2004.00126.x · Cited by 312 · see citing works
Yeşilova, Z., Yaman, H., Öktenli, Ç., Özcan, A., Uygun, A., Çakır, E., Sanisoğlu, S. Y., Erdil, A., Ateş, Y., Aslan, M., et al. (2005) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2005.41500.x · Cited by 290 · see citing works
Hsu, C., & Yen, G. (2007) · British Journal Of Nutrition · doi:10.1017/s000711450774686x · Cited by 279 · see citing works
“Mehta et al. 55 indicated that HFD lead to liver injury and insulin resistance through oxidative stress.”
BackgroundChurch, T. S., Kuk, J. L., Ross, R., Priest, E. L., Biltoff, E., & Blair, S. N. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.03.019 · Cited by 268 · see citing works
Features, Diagnosis, and Treatment of Nonalcoholic Fatty Liver Disease
Torres, D. M., Williams, C. D., & Harrison, S. A. (2012) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2012.03.011 · Cited by 269 · see citing works
Qiu, Y.-Y., Zhang, J., Zeng, F.-Y., & Zhu, Y. Z. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106786 · Cited by 271 · see citing works
Gutiérrez-Grobe, Y., Ponciano‐Rodríguez, G., Ramos, M. H., Uribe, M., & Méndez‐Sánchez, N. (2010) · Annals of Hepatology · doi:10.1016/s1665-2681(19)31616-3 · Cited by 246 · see citing works
Cao, J., Dai, D.-L., Long, Y., et al. (2012) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-011-1211-9 · Cited by 241 · see citing works
“Nevertheless, it is unclear how triglyceride accumulation causes inflammation or at the late stage, cirrhosis, although recent studies demonstrated that oxidative stress and cytokines are involved in the process [1, 3–5].”
BackgroundSerum cytokine and soluble cytokine receptor levels in patients with non‐alcoholic steatohepatitis
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 · see citing works
“Several factors are considered to be involved in the inflammatory responses of NASH (4), and cytokine is one of the candidates that promote progression to steatohepatitis (5).”
BackgroundUrsodeoxycholic Acid and Atorvastatin in the Treatment of Nonalcoholic Steatohepatitis
Kıyıcı, M., Gülten, M., Gurel, S., Nak, S. G., Dolar, E., Savcı, G., Adım, Ş. B., Yerci, Ö., & Memik, F. (2003) · Canadian Journal of Gastroenterology · doi:10.1155/2003/857869 · Cited by 199 · see citing works
“Strict diets for weight reduction, antioxidant therapies such as vitamin C and vitamin E (8,9), control of diabetes and/or hyperlipidemia and UDCA treatment have also been tried to counter these effects.”
BackgroundNonalcoholic steatohepatitis: a search for factual animal models
Sanches, S. C. L., Ramalho, L. N. Z., Augusto, M. J., da Silva, D. M., & Ramalho, F. S. (2015) · BioMed Research International · doi:10.1155/2015/574832 · Cited by 174 · see citing works
“Hyperinsulinemia intensifies the hepatic synthesis of fatty acids by inducing glycolysis and favors the accumulation of triglycerides within hepatocytes by decreasing the liver ability to reesterify and export triglycerides [8, 9].”
Zheng, Y., Wang, S., Wu, J., & Wang, Y. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04367-1 · Cited by 192 · see citing works
Valtueña, S., Pellegrini, N., Franzini, L., Bianchi, M. A., Ardigò, D., Rio, D. D., Piatti, P., Scazzina, F., Zavaroni, I., & Brighenti, F. (2008) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/87.5.1290 · Cited by 171 · see citing works
Gallic Acid Ameliorated Impaired Glucose and Lipid Homeostasis in High Fat Diet-Induced NAFLD Mice
Chao, J., Huo, T., Cheng, H.-Y., Tsai, J.-C., Liao, J., Lee, M., Qin, X.-M., Hsieh, M., Pao, L., & Peng, W. (2014) · PLoS ONE · doi:10.1371/journal.pone.0096969 · Cited by 169 · see citing works
“In the present study, we noted that there was a significantly decreased level of serum glutamate and glutamine in the HFD-fed mice (Table 1 and Table 3), which probably reflects the presence of the HFD-induced promotion of oxidative stress [65].”
BackgroundEzetimibe improves high fat and cholesterol diet-induced non-alcoholic fatty liver disease in mice
Zheng, S., Hoos, L. M., Cook, J., Tetzloff, G. G., Davis, H. R., van Heek, M., & Hwa, J. J. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.01.045 · Cited by 163 · see citing works
Cojocaru, K.-A., Luchian, I. A., Goriuc, A., Antoci, L.-M., Ciobanu, C.-G., Popescu, R. M., Vlad, C.-E., Blaj, M., & Foia, L. G. (2023) · Antioxidants · doi:10.3390/antiox12030658 · Cited by 151 · see citing works
“An increase in antioxidants, such as vitamin E, vitamin C, coenzyme Q, and N-acetylcysteine (NAC), is indicated for their oxidative stress reduction [133,134].”
BackgroundLaurent, A., Nicco, C., Nhieu, J. T. V., Borderie, D., Chéreau, C., Conti, F., Jaffray, P., Soubrane, O., Calmus, Y., Weill, B. J., et al. (2004) · Hepatology · doi:10.1002/hep.20177 · Cited by 120 · see citing works
Dietary glycemic index and liver steatosis
Valtueña, S., Pellegrini, N., Ardigò, D., Rio, D. D., Numeroso, F., Scazzina, F., Monti, L. D., Zavaroni, I., & Brighenti, F. (2006) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/84.1.136 · Cited by 120 · see citing works
Baumgardner, J. N., Shankar, K., Hennings, L. J., Badger, T. M., & Ronis, M. J. J. (2007) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00296.2007 · Cited by 121 · see citing works
Loguercio, C., Federico, A., Trappoliere, M., Tuccillo, C., de Sio, I., Di Leva, A., Niosi, M., D’Auria, M. V., Capasso, R., Blanco, C. D. V., et al. (2007) · Digestive Diseases and Sciences · doi:10.1007/s10620-006-9703-2 · Cited by 116 · see citing works
“Therefore, antioxidants may be useful antifibrotic agents [35].”
BackgroundMitochondrial oxidative stress and inflammation: an slalom to obesity and insulin resistance
Martínez, J. A. (2006) · Journal of Physiology and Biochemistry · doi:10.1007/bf03165759 · Cited by 112 · see citing works
Taitano, A. A., Markow, M., Finan, J. E., Wheeler, D. E., Gonzalvo, J. P., & Murr, M. M. (2014) · Journal of Gastrointestinal Surgery · doi:10.1007/s11605-014-2678-y · Cited by 112 · see citing works
Intermediate filament cytoskeleton of the liver in health and disease
Strnad, P., Stumptner, C., Zatloukal, K., & Denk, H. (2008) · Histochemistry and Cell Biology · doi:10.1007/s00418-008-0431-x · Cited by 111 · see citing works
“mice cause elevated levels of oxidative stress (Tephly et al. 1981; Mehta et al. 2002; Dey and Cederbaum 2006; Farrell and Larter 2006) and MDBs themselves were shown to contain misfolded keratins with increased -sheet formation (Cadrin et al.”
BackgroundInsulin resistance in development and progression of nonalcoholic fatty liver disease
Alam, S., Mustafa, G., Alam, M., & Ahmad, N. (2016) · World Journal of Gastrointestinal Pathophysiology · doi:10.4291/wjgp.v7.i2.211 · Cited by 108 · see citing works
Go, E. K., Jung, K. J., Kim, J. Y., Yu, B. P., & Chung, H. Y. (2005) · The Journals of Gerontology Series A · doi:10.1093/gerona/60.10.1252 · Cited by 109 · see citing works
“In addition, betaine is shown to be beneficial in the treatment of nonalcoholic fatty liver disease (7).”
BackgroundHuang, C.-Z., Tung, Y., Hsia, S., Wu, C., & Yen, G. (2017) · Food & Function · doi:10.1039/c6fo01585a · Cited by 110 · see citing works
de Oliveira, C. P. M. S., Stefano, J. T., de Siqueira, É. R. F., Silva, L. S., Mazo, D. F. D. C., de Lima, V. M. R., Junior, C. K. F., de Mello, E. S., Souza, F., Rabelo, F., et al. (2007) · Hepatology Research · doi:10.1111/j.1872-034x.2007.00215.x · Cited by 109 · see citing works
Wang, L., Chen, L., Tan, Y., Wei, J., Chang, Y., Jin, T., & Zhu, H. (2013) · Lipids in Health and Disease · doi:10.1186/1476-511x-12-34 · Cited by 109 · see citing works
“The expression of hepatic PPARα expression has shown to be down-regulated in NAFLD patients [4], ApoE−/− mice also exhibited reduced hepatic PPARα expression compared with WT mice though without statistical significance in our present study.”
BackgroundInfluentialYan, M.-X., Li, Y., Meng, M., Ren, H., & Kou, Y. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.06.063 · Cited by 107 · see citing works
Santiago, J. V. A., Jayaraman, J., Shenbagam, M., & Nalini, N. (2011) · European Journal of Nutrition · doi:10.1007/s00394-011-0182-7 · Cited by 103 · see citing works
“inducing vicious cycles of oxidative injury leading to inflammation and fibrosis [46].”
BackgroundBinge ethanol exposure increases liver injury in obese rats
Carmiel-Haggai, M., Cederbaum, A. I., & Nieto, N. (2003) · Gastroenterology · doi:10.1053/j.gastro.2003.09.019 · Cited by 103 · see citing works
Thymosin alpha 1 attenuates lipid peroxidation and improves fructose-induced steatohepatitis in rats
Armutçu, F., Çoşkun, Ö., Gürel, A., Kanter, M., Can, M., Uçar, F., & Ünalacak, M. (2005) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2005.01.013 · Cited by 102 · see citing works
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 101 · see citing works
Arbutin alleviates fatty liver by inhibiting ferroptosis via FTO/SLC7A11 pathway
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 · see citing works
“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 · see citing works
“In 65– 95% of patients, levels of alanine transaminase (ALT) are higher than those of aspartate transaminase (AST) (patients A and B) [6,26].”
BackgroundLipotoxicity in HepG2 cells triggered by free fatty acids.
(2011) · PubMed Central · Cited by 94 · see citing works
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 · see citing works
“Some studies have shown that liver injury is mediated by oxidative stress (3,4), endotoxins, cytokines (5,6), and hyperinsulinemia (7,8).”
BackgroundFiorini, 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 · see citing works
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 · see citing works
“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 [ ,”
BackgroundWang, Y., Zhou, M., Lam, K. S. L., & Xu, A. (2009) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302009000200012 · Cited by 88 · see citing works
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 · see citing works
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 83 · see citing works
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 83 · see citing works
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 81 · see citing works
“currently are not well understood [3,6,8,9].”
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 · see citing works
Mitochondrial superoxide/hydrogen peroxide: An emerging therapeutic target for metabolic diseases
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 · see citing works
Hutchinson, C. (2016) · European Journal of Nutrition · doi:10.1007/s00394-016-1155-7 · Cited by 76 · see citing works
“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].”
ResultAssociation 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 · see citing works
“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…”
BackgroundYakaryılmaz, 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 · see citing works
Regressive Effect of Myricetin on Hepatic Steatosis in Mice Fed a High-Fat Diet
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 · see citing works
“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.”
BackgroundInfluentialGlutathione‐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 · see citing works
Fatty liver induced by free radicals and lipid peroxidation
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 75 · see citing works
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 72 · see citing works
Hussein, O., Grosovski, M., Schlesinger, S., Szvalb, S., & Assy, N. (2007) · Digestive Diseases and Sciences · doi:10.1007/s10620-006-9631-1 · Cited by 71 · see citing works
“, oxidative stress/ lipid peroxidation, and tumor necrosis factor α (TNFα)/endotoxinmediated injury [17].”
BackgroundNoh, 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 · see citing works
“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…”
BackgroundMitochondrial 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 67 · see citing works
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 · see citing works
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 · see citing works
“Clinical studies also reported that hyperglycemia enhances the pathogenicity of liver disease through increasing oxidative stress.(29,30) Patients with diabetes FIG.”
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 · see citing works
“Additional factors involved in the pathogenesis of NAFLD are obesity and obesity-relatedmetabolic disorders (6, 7).”
BackgroundCichoż‐Lach, H., Celiński, K., Konturek, P. C., Konturek, S. J., & Słomka, M. (2010) · PubMed · Cited by 62 · see citing works
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 61 · see citing works
Minor, T., Stegemann, J., Hirner, A., et al. (2009) · Liver Transplantation · doi:10.1002/lt.21751 · Cited by 60 · see citing works
“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…”
BackgroundBhatti, 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 60 · see citing works
Assy, N. (2005) · World Journal of Gastroenterology · doi:10.3748/wjg.v11.i37.5834 · Cited by 60 · see citing works
“Recently, two additional mechanisms were reported: oxidative stress/lipid peroxidation; and TNF-α/ endotoxin-mediated injuries[ 7 ].”
BackgroundTahan, V., Atuğ, Ö., Akın, H., et al. (2009) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2009.00676.x · Cited by 58 · see citing works
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 57 · see citing works
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 · see citing works
“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).”
InfluentialGraham, 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 · see citing works
Subcutaneous vitamin E ameliorates liver injury in an in vivo model of steatocholestasis†‡
Soden, J. S., Devereaux, M. W., Haas, J. E., et al. (2007) · Hepatology · doi:10.1002/hep.21690 · Cited by 54 · see citing works
“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.”
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 54 · see citing works
Pan, Z.-G., & An, X.-S. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.02.115 · Cited by 50 · see citing works
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 · see citing works
“Steatosis, the hallmark of a feature of the nonalcoholic fatty liver disease, progresses to steatohepatitis, eventually to cirrhosis [47].”
BackgroundIdentification 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 · see citing works
“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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
“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].”
BackgroundInterstrain 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 · see citing works
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 · see citing works
“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…”
BackgroundTung, 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 · see citing works
“[3] Mehta K, Van Thiel DH, Shah N, Mobarhan S.”
BackgroundDebnath, S., Ghosh, S., & Hazra, B. (2013) · Food and Chemical Toxicology · doi:10.1016/j.fct.2013.06.036 · Cited by 43 · see citing works
Jaiswal, V. K., & Lee, H. (2022) · Antioxidants · doi:10.3390/antiox11122494 · Cited by 41 · see citing works
“Therefore, antioxidants that are used against these diseases were found to be effective [25,26].”
BackgroundNovel 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 · see citing works
“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].”
BackgroundKarbiner, M. S., Sierra, L., Minahk, C. J., et al. (2013) · Life Sciences · doi:10.1016/j.lfs.2013.08.003 · Cited by 39 · see citing works
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 · see citing works
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 39 · see citing works
“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].”
BackgroundMedical 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 39 · see citing works
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 · see citing works
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 38 · see citing works
“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.”
BackgroundRetractedDemircioğlu, 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 37 · see citing works
“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
- 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 › Epidemiology › 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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