Metabolic dysfunction-associated steatotic liver disease (MASLD) is a heterogeneous condition characterized by liver steatosis, inflammation, consequent fibrosis, and cirrhosis. Chronic impairment of lipid metabolism is closely related to oxidative stress, leading to cellular lipotoxicity, mitochondrial dysfunction, and endoplasmic reticulum stress. The detrimental effect of oxidative stress is usually accompanied by changes in antioxidant defense mechanisms, with the alterations in antioxidant enzymes expression/activities during MASLD development and progression reported in many clinical and experimental studies. This review will provide a comprehensive overview of the present research on MASLD-induced changes in the catalytic activity and expression of the main antioxidant enzymes (superoxide dismutases, catalase, glutathione peroxidases, glutathione S-transferases, glutathione reductase, NAD(P)H:quinone oxidoreductase) and in the level of non-enzymatic antioxidant glutathione. Furthermore, an overview of the therapeutic effects of vitamin E on antioxidant enzymes during the progression of MASLD will be presented. Generally, at the beginning of MASLD development, the expression/activity of antioxidant enzymes usually increases to protect organisms against the increased production of reactive oxygen species. However, in advanced stage of MASLD, the expression/activity of several antioxidants generally decreases due to damage to hepatic and extrahepatic cells, which further exacerbates the damage. Although the results obtained in patients, in various experimental animal or cell models have been inconsistent, taken together the importance of antioxidant enzymes in MASLD development and progression has been clearly shown.

Department of Biochemical Sciences Faculty of Pharmacy in Hradec Králové Charles University 500 05 Hradec Králové Czech Republic

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Adachi T, Wang J, Wang XL (2000) Age-related change of plasma extracellular-superoxide dismutase. Clin Chim Acta 290(2):169–178. 10.1016/s0009-8981(99)00187-4 PubMed

Alfarisi HAH, Ibrahim MB, Mohamed ZBH, Azahari N, Hamdan AHB, Che Mohamad CA (2020) Hepatoprotective effects of a novel trihoney against nonalcoholic fatty liver disease: a comparative study with atorvastatin. ScientificWorldJournal 2020:4503253. 10.1155/2020/4503253 PubMed PMC

Alfonso-Prieto M, Biarnés X, Vidossich P, Rovira C (2009) The molecular mechanism of the catalase reaction. J Am Chem Soc 131(33):11751–11761. 10.1021/ja9018572 PubMed

Ali MH, Messiha BA, Abdel-Latif HA (2016) Protective effect of ursodeoxycholic acid, resveratrol, and N-acetylcysteine on nonalcoholic fatty liver disease in rats. Pharm Biol 54(7):1198–1208. 10.3109/13880209.2015.1060247 PubMed

Aljomah G, Baker SS, Liu W et al (2015) Induction of CYP2E1 in non-alcoholic fatty liver diseases. Exp Mol Pathol 99(3):677–681. 10.1016/j.yexmp.2015.11.008 PubMed PMC

Al-Serri A, Anstee QM, Valenti L et al (2012) The SOD2 C47T polymorphism influences NAFLD fibrosis severity: evidence from case-control and intra-familial allele association studies. J Hepatol 56(2):448–454. 10.1016/j.jhep.2011.05.029 PubMed

An MY, Lee SR, Hwang HJ, Yoon JG, Lee HJ, Cho JA (2021) Antioxidant and anti-inflammatory effects of korean black ginseng extract through ER stress pathway. Antioxidants (Basel). 10.3390/antiox10010062 PubMed PMC

Arroyave-Ospina JC, Wu Z, Geng Y, Moshage H (2021) Role of oxidative stress in the pathogenesis of non-alcoholic fatty liver disease: implications for prevention and therapy. Antioxidants (Basel). 10.3390/antiox10020174 PubMed PMC

Asghari S, Hamedi-Shahraki S, Amirkhizi F (2020) Systemic redox imbalance in patients with nonalcoholic fatty liver disease. Eur J Clin Invest 50(4):e13211. 10.1111/eci.13211 PubMed

Ashla AA, Hoshikawa Y, Tsuchiya H et al (2010) Genetic analysis of expression profile involved in retinoid metabolism in non-alcoholic fatty liver disease. Hepatol Res 40(6):594–604. 10.1111/j.1872-034X.2010.00646.x PubMed

Asikainen TM, Raivio KO, Saksela M, Kinnula VL (1998) Expression and developmental profile of antioxidant enzymes in human lung and liver. Am J Respir Cell Mol Biol 19(6):942–949. 10.1165/ajrcmb.19.6.3248 PubMed

Bai Y, Li T, Liu J et al (2023) Aerobic exercise and vitamin E improve high-fat diet-induced NAFLD in rats by regulating the AMPK pathway and oxidative stress. Eur J Nutr 62(6):2621–2632. 10.1007/s00394-023-03179-9 PubMed

Baker SS, Baker RD, Liu W, Nowak NJ, Zhu L (2010) Role of alcohol metabolism in non-alcoholic steatohepatitis. PLoS ONE 5(3):e9570. 10.1371/journal.pone.0009570 PubMed PMC

Barbosa PO, Souza MO, Silva MPS et al (2021) Açaí (Euterpe oleracea Martius) supplementation improves oxidative stress biomarkers in liver tissue of dams fed a high-fat diet and increases antioxidant enzymes’ gene expression in offspring. Biomed Pharmacother 139:111627. 10.1016/j.biopha.2021.111627 PubMed

Boland ML, Oldham S, Boland BB et al (2018) Nonalcoholic steatohepatitis severity is defined by a failure in compensatory antioxidant capacity in the setting of mitochondrial dysfunction. World J Gastroenterol 24(16):1748–1765. 10.3748/wjg.v24.i16.1748 PubMed PMC

Bousova I, Kostakova S, Matouskova P, Bartikova H, Szotakova B, Skalova L (2017) Monosodium glutamate-induced obesity changed the expression and activity of glutathione S-transferases in mouse heart and kidney. Pharmazie 72(5):257–259. 10.1691/ph.2017.6886 PubMed

Boušová I, Skálová L (2012) Inhibition and induction of glutathione S-transferases by flavonoids: possible pharmacological and toxicological consequences. Drug Metab Rev 44(4):267–286. 10.3109/03602532.2012.713969 PubMed

Brigelius-Flohe R, Maiorino M (2013) Glutathione peroxidases. Biochem Biophys Acta 1830(5):3289–3303. 10.1016/j.bbagen.2012.11.020 PubMed

Buzzetti E, Pinzani M, Tsochatzis EA (2016) The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism 65(8):1038–1048. 10.1016/j.metabol.2015.12.012 PubMed

Cai YQ, Zhang LZ, Wang DJ et al (2014) Effect of Nrf2 and related factors on the progression of nonalcoholic steatohepatitis. Zhongguo Ying Yong Sheng Li Xue Za Zhi 30(5):465–470 PubMed

Campo L, Eiseler S, Apfel T, Pyrsopoulos N (2019) Fatty liver disease and gut microbiota: a comprehensive update. J Clin Transl Hepatol 7(1):56–60. 10.14218/JCTH.2018.00008 PubMed PMC

Carmiel-Haggai M, Cederbaum AI, Nieto N (2005) A high-fat diet leads to the progression of non-alcoholic fatty liver disease in obese rats. Faseb j 19(1):136–138. 10.1096/fj.04-2291fje PubMed

Carvalho MMF, Reis LLT, Lopes JMM et al (2018) Açai improves non-alcoholic fatty liver disease (NAFLD) induced by fructose. Nutr Hosp 35(2):318–325. 10.20960/nh.1294 PubMed

Chalasani N, Younossi Z, Lavine JE et al (2018) The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology 67(1):328–357. 10.1002/hep.29367 PubMed

Chaves Cayuela N, Kiyomi Koike M, Jacysyn JF et al (2020) N-acetylcysteine reduced ischemia and reperfusion damage associated with steatohepatitis in mice. Int J Mol ScI. 10.3390/ijms21114106 PubMed PMC

Chen G, Xu R, Zhang S et al (2015) CYP2J2 overexpression attenuates nonalcoholic fatty liver disease induced by high-fat diet in mice. Am J Physiol Endocrinol Metab 308(2):E97-e110. 10.1152/ajpendo.00366.2014 PubMed PMC

Chen J, Liu J, Wang Y et al (2017) Wogonin mitigates nonalcoholic fatty liver disease via enhancing PPARα/AdipoR2, in vivo and in vitro. Biomed Pharmacother 91:621–631. 10.1016/j.biopha.2017.04.125 PubMed

Chen YM, Lian CF, Sun QW et al (2022) Ramulus Mori (Sangzhi) alkaloids alleviate high-fat diet-induced obesity and nonalcoholic fatty liver disease in mice. Antioxidants (Basel). 10.3390/antiox11050905 PubMed PMC

Chenna H, Khelef Y, Halimi I et al (2024) Potential hepatoprotective effect of matricaria pubescens on high-fat diet-induced non-alcoholic fatty liver disease in rats. Chem Biodivers 21(4):e202302005. 10.1002/cbdv.202302005 PubMed

Chua D, Low ZS, Cheam GX, Ng AS, Tan NS (2022) Utility of Human Relevant Preclinical Animal Models in Navigating NAFLD to MAFLD Paradigm. International journal of molecular sciences 23(23) 10.3390/ijms232314762 PubMed PMC

Couto N, Wood J, Barber J (2016) The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Radical Biol Med 95:27–42. 10.1016/j.freeradbiomed.2016.02.028 PubMed

Dai N, Zou Y, Zhu L, Wang HF, Dai MG (2014) Antioxidant properties of proanthocyanidins attenuate carbon tetrachloride (CCl4)-induced steatosis and liver injury in rats via CYP2E1 regulation. J Med Food 17(6):663–669. 10.1089/jmf.2013.2834 PubMed PMC

Daly AK (2013) Relevance of CYP2E1 to non-alcoholic fatty liver disease. Subcell Biochem 67:165–175. 10.1007/978-94-007-5881-0_5 PubMed

Das KS, Balakrishnan V, Mukherjee S, Vasudevan DM (2008) Evaluation of blood oxidative stress-related parameters in alcoholic liver disease and non-alcoholic fatty liver disease. Scand J Clin Lab Invest 68(4):323–334. 10.1080/00365510701673383 PubMed

de Freitas Carvalho MM, Lage NN, de Souza Paulino AH et al (2019) Effects of açai on oxidative stress, ER stress, and inflammation-related parameters in mice with high fat diet-fed induced NAFLD. Sci Rep 9(1):8107. 10.1038/s41598-019-44563-y PubMed PMC

Delli Bovi AP, Marciano F, Mandato C, Siano MA, Savoia M, Vajro P (2021) Oxidative stress in non-alcoholic fatty liver disease an updated mini review. Front Med (Lausanne) 8:595371. 10.3389/fmed.2021.595371 PubMed PMC

Deng Y, Tang K, Chen R et al (2019) Berberine attenuates hepatic oxidative stress in rats with non-alcoholic fatty liver disease via the Nrf2/ARE signalling pathway. Exp Ther Med 17(3):2091–2098. 10.3892/etm.2019.7208 PubMed PMC

Desai S, Baker SS, Liu W et al (2014) Paraoxonase 1 and oxidative stress in paediatric non-alcoholic steatohepatitis. Liver Int 34(1):110–117. 10.1111/liv.12308 PubMed

Dong L, Han X, Tao X et al (2018) Protection by the Total Flavonoids from Rosa laevigata Michx Fruit against Lipopolysaccharide-Induced Liver Injury in Mice via Modulation of FXR Signaling. Foods. 10.3390/foods7060088 PubMed PMC

Du J, Zhang M, Lu J et al (2016) Osteocalcin improves nonalcoholic fatty liver disease in mice through activation of Nrf2 and inhibition of JNK. Endocrine 53(3):701–709. 10.1007/s12020-016-0926-5 PubMed

Endo H, Niioka M, Kobayashi N, Tanaka M, Watanabe T (2013) Butyrate-producing probiotics reduce nonalcoholic fatty liver disease progression in rats: new insight into the probiotics for the gut-liver axis. PLoS ONE 8(5):e63388. 10.1371/journal.pone.0063388 PubMed PMC

Fan H, Ma X, Lin P et al (2017) Scutellarin prevents nonalcoholic fatty liver disease (NAFLD) and Hyperlipidemia via PI3K/AKT-dependent activation of nuclear factor (Erythroid-Derived 2)-Like 2 (Nrf2) in Rats. Med Sci Monit 23:5599–5612. 10.12659/msm.907530 PubMed PMC

Feldstein AE, Werneburg NW, Canbay A et al (2004) Free fatty acids promote hepatic lipotoxicity by stimulating TNF-alpha expression via a lysosomal pathway. Hepatology 40(1):185–194. 10.1002/hep.20283 PubMed

Feng R, Luo C, Li C et al (2017) Free fatty acids profile among lean, overweight and obese non-alcoholic fatty liver disease patients: a case - control study. Lipids Health Dis 16(1):165. 10.1186/s12944-017-0551-1 PubMed PMC

Finer N (2022) Weight loss interventions and nonalcoholic fatty liver disease: optimizing liver outcomes. Diabetes Obes Metab 24(Suppl 2):44–54. 10.1111/dom.14569 PubMed

Fisher CD, Jackson JP, Lickteig AJ, Augustine LM, Cherrington NJ (2008) Drug metabolizing enzyme induction pathways in experimental non-alcoholic steatohepatitis. Arch Toxicol 82(12):959–964. 10.1007/s00204-008-0312-z PubMed PMC

Friedman SL, Neuschwander-Tetri BA, Rinella M, Sanyal AJ (2018) Mechanisms of NAFLD development and therapeutic strategies. Nat Med 24(7):908–922. 10.1038/s41591-018-0104-9 PubMed PMC

Fujii J, Osaki T, Bo T (2022) Ascorbate is a primary antioxidant in mammals. Molecules. 10.3390/molecules27196187 PubMed PMC

Furukawa S, Fujita T, Shimabukuro M et al (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 114(12):1752–1761. 10.1172/jci21625 PubMed PMC

Gao H, Cao Y, Xia H, Zhu X, Jin Y (2020) CYP4A11 is involved in the development of nonalcoholic fatty liver disease via ROS-induced lipid peroxidation and inflammation. Int J Mol Med 45(4):1121–1129. 10.3892/ijmm.2020.4479 PubMed PMC

Garcia CC, Piotrkowski B, Baz P et al (2022) A Decreased response to resistin in mononuclear leukocytes contributes to oxidative stress in nonalcoholic fatty liver disease. Dig Dis Sci 67(7):3006–3016. 10.1007/s10620-021-07105-z PubMed

García-Ruiz C, Fernández-Checa JC (2018) Mitochondrial oxidative stress and antioxidants balance in fatty liver disease. Hepatol Commun 2(12):1425–1439. 10.1002/hep4.1271 PubMed PMC

Gasparin FRS, Carreño FO, Mewes JM et al (2018) Sex differences in the development of hepatic steatosis in cafeteria diet-induced obesity in young mice. Biochim Biophys Acta Mol Basis Dis 1864(7):2495–2509. 10.1016/j.bbadis.2018.04.004 PubMed

Glorieux C, Calderon PB (2017) Catalase, a remarkable enzyme: targeting the oldest antioxidant enzyme to find a new cancer treatment approach. Biol Chem 398(10):1095–1108. 10.1515/hsz-2017-0131 PubMed

Gutiérrez-Cuevas J, Santos A, Armendariz-Borunda J (2021) Pathophysiological molecular mechanisms of obesity: a link between MAFLD and NASH with cardiovascular diseases. Int J Mol Sci. 10.3390/ijms222111629 PubMed PMC

Halliwell B (2014) Cell culture, oxidative stress, and antioxidants: avoiding pitfalls. Biomed J 37(3):99–105. 10.4103/2319-4170.128725 PubMed

Halliwell B (2024) Understanding mechanisms of antioxidant action in health and disease. Nat Rev Mol Cell Biol 25(1):13–33. 10.1038/s41580-023-00645-4 PubMed

Hanafi MY, Zaher ELM, El-Adely SEM et al (2018) The therapeutic effects of bee venom on some metabolic and antioxidant parameters associated with HFD-induced non-alcoholic fatty liver in rats. Exp Ther Med 15(6):5091–5099. 10.3892/etm.2018.6028 PubMed PMC

Hannah WN Jr, Harrison SA (2016) Lifestyle and Dietary Interventions in the Management of Nonalcoholic Fatty Liver Disease. Dig Dis Sci 61(5):1365–1374. 10.1007/s10620-016-4153-y PubMed

Hansen HH, HM AE, Oro D, et al (2020) Human translatability of the GAN diet-induced obese mouse model of non-alcoholic steatohepatitis. BMC Gastroenterol 20(1):210. 10.1186/s12876-020-01356-2 PubMed PMC

Hardwick JP (2008) Cytochrome P450 omega hydroxylase (CYP4) function in fatty acid metabolism and metabolic diseases. Biochem Pharmacol 75(12):2263–2275. 10.1016/j.bcp.2008.03.004 PubMed

Hardwick RN, Fisher CD, Canet MJ, Lake AD, Cherrington NJ (2010) Diversity in antioxidant response enzymes in progressive stages of human nonalcoholic fatty liver disease. Drug Metab Dispos 38(12):2293–2301. 10.1124/dmd.110.035006 PubMed PMC

Hardy T, Oakley F, Anstee QM, Day CP (2016) Nonalcoholic fatty liver disease: pathogenesis and disease spectrum. Annu Rev Pathol 11:451–496. 10.1146/annurev-pathol-012615-044224 PubMed

Harjumaki R, Pridgeon CS, Ingelman-Sundberg M (2021) CYP2E1 in alcoholic and non-alcoholic liver injury roles of ROS reactive intermediates and lipid overload. Int J Mol Sci. 10.3390/ijms22158221 PubMed PMC

Ho YS, Xiong Y, Ma W, Spector A, Ho DS (2004) Mice lacking catalase develop normally but show differential sensitivity to oxidant tissue injury. J Biol Chem 279(31):32804–32812. 10.1074/jbc.M404800200 PubMed

Hotta K, Kitamoto T, Kitamoto A et al (2018) Identification of the genomic region under epigenetic regulation during non-alcoholic fatty liver disease progression. Hepatol Res 48(3):E320-e334. 10.1111/hepr.12992 PubMed

Hou C, Wang Y, Zhu E et al (2016) Coral calcium hydride prevents hepatic steatosis in high fat diet-induced obese rats: A potent mitochondrial nutrient and phase II enzyme inducer. Biochem Pharmacol 103:85–97. 10.1016/j.bcp.2015.12.020 PubMed

Huang YS, Chang CH, Lin TL, Perng CL (2014) Genetic variations of superoxide dismutase 2 and cytochrome P450 2E1 in non-alcoholic steatohepatitis. Liver Int 34(6):931–936. 10.1111/liv.12533 PubMed

Huang F, Wang J, Yu F et al (2018) Protective effect of meretrix meretrix oligopeptides on high-fat-diet-induced non-alcoholic fatty liver disease in mice. Mar Drugs. 10.3390/md16020039 PubMed PMC

Huang YS, Chang TE, Perng CL, Huang YH (2021) Genetic variations of three important antioxidative enzymes SOD2, CAT, and GPX1 in nonalcoholic steatohepatitis. J Chin Med Assoc 84(1):14–18. 10.1097/jcma.0000000000000437 PubMed

Im YR, Hunter H, de Gracia HD et al (2021) A systematic review of animal models of NAFLD finds high-fat, high-fructose diets most closely resemble human NAFLD. Hepatology 74(4):1884–1901. 10.1002/hep.31897 PubMed

Ip E, Farrell GC, Robertson G, Hall P, Kirsch R, Leclercq I (2003) Central role of PPARalpha-dependent hepatic lipid turnover in dietary steatohepatitis in mice. Hepatology 38(1):123–132. 10.1053/jhep.2003.50307 PubMed

Jain MR, Giri SR, Bhoi B et al (2018) Dual PPARα/γ agonist saroglitazar improves liver histopathology and biochemistry in experimental NASH models. Liver Int 38(6):1084–1094. 10.1111/liv.13634 PubMed PMC

Jakubek P, Kalinowski P, Karkucinska-Wieckowska A et al (2024) Oxidative stress in metabolic dysfunction-associated steatotic liver disease (MASLD): How does the animal model resemble human disease? FASEB J 38(3):e23466. 10.1096/fj.202302447R PubMed

Janevski M, Antonas KN, Sullivan-Gunn MJ, McGlynn MA, Lewandowski PA (2011) The effect of cocoa supplementation on hepatic steatosis, reactive oxygen species and LFABP in a rat model of NASH. Comp Hepatol 10(1):10. 10.1186/1476-5926-10-10 PubMed PMC

Jarukamjorn K, Jearapong N, Pimson C, Chatuphonprasert W (2016) A high-fat, high-fructose diet induces antioxidant imbalance and increases the risk and progression of nonalcoholic fatty liver disease in mice. Scientifica (Cairo) 2016:5029414. 10.1155/2016/5029414 PubMed PMC

Jha D, Mitra Mazumder P (2019) High fat diet administration leads to the mitochondrial dysfunction and selectively alters the expression of class 1 GLUT protein in mice. Mol Biol Rep 46(2):1727–1736. 10.1007/s11033-019-04623-y PubMed

Jiang J, Li H, Tang M et al (2024) Upregulation of hepatic glutathione s-transferase alpha 1 ameliorates metabolic dysfunction-associated steatosis by degrading fatty acid binding protein 1. Int J Mol Sci. 10.3390/ijms25105086 PubMed PMC

Jin M, Wei Y, Yu H et al (2021) Erythritol improves nonalcoholic fatty liver disease by activating Nrf2 antioxidant capacity. J Agric Food Chem 69(44):13080–13092. 10.1021/acs.jafc.1c05213 PubMed

Jomova K, Alomar SY, Alwasel SH, Nepovimova E, Kuca K, Valko M (2024) Several lines of antioxidant defense against oxidative stress: antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants. Arch Toxicol 98(5):1323–1367. 10.1007/s00204-024-03696-4 PubMed PMC

Jonas W, Schurmann A (2021) Genetic and epigenetic factors determining NAFLD risk. Mol Metab 50:101111. 10.1016/j.molmet.2020.101111 PubMed PMC

Jorgačević B, Mladenović D, Ninković M et al (2014) Dynamics of oxidative/nitrosative stress in mice with methionine-choline-deficient diet-induced nonalcoholic fatty liver disease. Hum Exp Toxicol 33(7):701–709. 10.1177/0960327113506723 PubMed

Jung JH, Kim HS (2013) The inhibitory effect of black soybean on hepatic cholesterol accumulation in high cholesterol and high fat diet-induced non-alcoholic fatty liver disease. Food Chem Toxicol 60:404–412. 10.1016/j.fct.2013.07.048 PubMed

Kanoni S, Kumar S, Amerikanou C et al (2021) Nutrigenetic interactions might modulate the antioxidant and anti-inflammatory status in mastiha-supplemented patients with NAFLD. Front Immunol 12:683028. 10.3389/fimmu.2021.683028 PubMed PMC

Ke Z, Tan S, Li H et al (2022) Tangeretin improves hepatic steatosis and oxidative stress through the Nrf2 pathway in high fat diet-induced nonalcoholic fatty liver disease mice. Food Funct 13(5):2782–2790. 10.1039/d1fo02989d PubMed

Kim B, Woo MJ, Park CS et al (2017) Hovenia Dulcis Extract Reduces Lipid Accumulation in Oleic Acid-Induced Steatosis of Hep G2 Cells via Activation of AMPK and PPARα/CPT-1 Pathway and in Acute Hyperlipidemia Mouse Model. Phytother Res 31(1):132–139. 10.1002/ptr.5741 PubMed

Kim HJ, Lee Y, Fang S, Kim W, Kim HJ, Kim JW (2020) GPx7 ameliorates non-alcoholic steatohepatitis by regulating oxidative stress. BMB Rep 53(6):317–322. 10.5483/BMBRep.2020.53.6.280 PubMed PMC

Kohjima M, Enjoji M, Higuchi N et al (2007) Re-evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease. Int J Mol Med 20(3):351–358 PubMed

Korinkova L, Prazienkova V, Cerna L et al (2020) Pathophysiology of NAFLD and NASH in experimental models: the role of food intake regulating peptides. Front Endocrinol 11:597583. 10.3389/fendo.2020.597583 PubMed PMC

Korish AA, Arafah MM (2013) Camel milk ameliorates steatohepatitis, insulin resistance and lipid peroxidation in experimental non-alcoholic fatty liver disease. BMC Complement Altern Med 13:264. 10.1186/1472-6882-13-264 PubMed PMC

Koruk M, Taysi S, Savas MC, Yilmaz O, Akcay F, Karakok M (2004) Oxidative stress and enzymatic antioxidant status in patients with nonalcoholic steatohepatitis. Ann Clin Lab Sci 34(1):57–62 PubMed

Kosmalski M, Szymczak-Pajor I, Drzewoski J, Sliwinska A (2023) Non-alcoholic fatty liver disease is associated with a decreased catalase (CAT) Level, CT Genotypes and the T Allele of the -262 C/T CAT Polymorphism. Cells. 10.3390/cells12182228 PubMed PMC

Krishnan A, Abdullah TS, Mounajjed T et al (2017) A longitudinal study of whole body, tissue, and cellular physiology in a mouse model of fibrosing NASH with high fidelity to the human condition. Am J Physiol Gastrointest Liver Physiol 312(6):G666-g680. 10.1152/ajpgi.00213.2016 PubMed PMC

Kroetz DL, Yook P, Costet P, Bianchi P, Pineau T (1998) Peroxisome proliferator-activated receptor alpha controls the hepatic CYP4A induction adaptive response to starvation and diabetes. J Biol Chem 273(47):31581–31589. 10.1074/jbc.273.47.31581 PubMed

Kumar A, Sharma A, Duseja A et al (2013) Patients with nonalcoholic fatty liver disease (NAFLD) have higher oxidative stress in comparison to chronic viral hepatitis. J Clin Exp Hepatol 3(1):12–18. 10.1016/j.jceh.2012.10.009 PubMed PMC

Lee CY, Lee CL (2021) Comparison of the improvement effect of deep ocean water with different mineral composition on the high fat diet-induced blood lipid and nonalcoholic fatty liver disease in a mouse model. Nutrients. 10.3390/nu13051732 PubMed PMC

Lee DH, Han DH, Nam KT et al (2016) Ezetimibe, an NPC1L1 inhibitor, is a potent Nrf2 activator that protects mice from diet-induced nonalcoholic steatohepatitis. Free Radical Biol Med 99:520–532. 10.1016/j.freeradbiomed.2016.09.009 PubMed

Li W, Lu Y (2018) Hepatoprotective Effects of Sophoricoside against Fructose-Induced Liver Injury via Regulating Lipid Metabolism, Oxidation, and Inflammation in Mice. J Food Sci 83(2):552–558. 10.1111/1750-3841.14047 PubMed

Li L, Hai J, Li Z et al (2014) Resveratrol modulates autophagy and NF-κB activity in a murine model for treating non-alcoholic fatty liver disease. Food Chem Toxicol 63:166–173. 10.1016/j.fct.2013.08.036 PubMed

Li H, Toth E, Cherrington NJ (2018) Alcohol Metabolism in the Progression of Human Nonalcoholic Steatohepatitis. Toxicol Sci 164(2):428–438. 10.1093/toxsci/kfy106 PubMed PMC

Li N, Sun YR, He LB et al (2020) Amelioration by Idesia polycarpa Maxim. Var. vestita Diels. of oleic acid-induced nonalcoholic fatty liver in HepG2 cells through antioxidant and modulation of lipid metabolism. Oxid Med Cell Longev 2020:1208726. 10.1155/2020/1208726 PubMed PMC

Li J, Wang T, Liu P et al (2021) Hesperetin ameliorates hepatic oxidative stress and inflammation via the PI3K/AKT-Nrf2-ARE pathway in oleic acid-induced HepG2 cells and a rat model of high-fat diet-induced NAFLD. Food Funct 12(9):3898–3918. 10.1039/d0fo02736g PubMed

Lickteig AJ, Fisher CD, Augustine LM, Cherrington NJ (2007) Genes of the antioxidant response undergo upregulation in a rodent model of nonalcoholic steatohepatitis. J Biochem Mol Toxicol 21(4):216–220. 10.1002/jbt.20177 PubMed

Liu YT, Chen HW, Lii CK et al (2020) A diterpenoid, 14-Deoxy-11, 12-didehydroandrographolide, in andrographis paniculata reduces steatohepatitis and liver injury in mice fed a high-fat and high-cholesterol Diet. Nutrients. 10.3390/nu12020523 PubMed PMC

Longhitano L, Distefano A, Musso N et al (2024) (+)-Lipoic acid reduces mitochondrial unfolded protein response and attenuates oxidative stress and aging in an in vitro model of non-alcoholic fatty liver disease. J Transl Med 22(1):82. 10.1186/s12967-024-04880-x PubMed PMC

Lou D, Fang Q, He Y et al (2024) Oxymatrine alleviates high-fat diet/streptozotocin-induced non-alcoholic fatty liver disease in C57BL/6 J mice by modulating oxidative stress, inflammation and fibrosis. Biomed Pharmacother 174:116491. 10.1016/j.biopha.2024.116491 PubMed

Lu JH, Hsia K, Lin CH, Chen CC, Yang HY, Lin MH (2019) Dietary supplementation with hazelnut oil reduces serum hyperlipidemia and ameliorates the progression of nonalcoholic fatty liver disease in hamsters fed a high-cholesterol diet. Nutrients. 10.3390/nu11092224 PubMed PMC

Ma C, Liu Y, He S et al (2020) Association between leukocyte mitochondrial DNA copy number and non-alcoholic fatty liver disease in a chinese population is mediated by 8-Oxo-2ʹ-deoxyguanosine. Front Med (Lausanne) 7:536. 10.3389/fmed.2020.00536 PubMed PMC

Ma Y, Lee G, Heo SY, Roh YS (2021) Oxidative stress is a key modulator in the development of nonalcoholic fatty liver disease. Antioxidants (Basel). 10.3390/antiox11010091 PubMed PMC

Malaguarnera L, Madeddu R, Palio E, Arena N, Malaguarnera M (2005) Heme oxygenase-1 levels and oxidative stress-related parameters in non-alcoholic fatty liver disease patients. J Hepatol 42(4):585–591. 10.1016/j.jhep.2004.11.040 PubMed

Marinho PC, Vieira AB, Pereira PG et al (2018) Capybara oil improves hepatic mitochondrial dysfunction, steatosis, and inflammation in a murine model of nonalcoholic fatty liver disease. Evid Based Complement Altern Med : Ecam 2018:4956079. 10.1155/2018/4956079 PubMed PMC

Masarone M, Rosato V, Dallio M et al (2018) Role of oxidative stress in pathophysiology of nonalcoholic fatty liver disease. Oxid Med Cell Longev 2018:9547613. 10.1155/2018/9547613 PubMed PMC

Matouskova P, Bartikova H, Bousova I, Levorova L, Szotakova B, Skalova L (2015) Drug-metabolizing and antioxidant enzymes in monosodium L-glutamate obese mice. Drug Metab Dispos 43(2):258–265. 10.1124/dmd.114.061176 PubMed

Matoušková P, Hanousková B, Skálová L (2018) MicroRNAs as potential regulators of glutathione peroxidases expression and their role in obesity and related pathologies. Int J Mol Sci. 10.3390/ijms19041199 PubMed PMC

Mendes IKS, Matsuura C, Aguila MB et al (2018) Weight loss enhances hepatic antioxidant status in a NAFLD model induced by high-fat diet. Appl Physiol Nutr Metab 43(1):23–29. 10.1139/apnm-2017-0317 PubMed

Miao L, St Clair DK (2009) Regulation of superoxide dismutase genes: implications in disease. Free Radical Biol Med 47(4):344–356. 10.1016/j.freeradbiomed.2009.05.018 PubMed PMC

Middelkoop E, Wiemer EA, Schoenmaker DE, Strijland A, Tager JM (1993) Topology of catalase assembly in human skin fibroblasts. Biochem Biophys Acta 1220(1):15–20. 10.1016/0167-4889(93)90091-3 PubMed

Mondola P, Damiano S, Sasso A, Santillo M (2016) The Cu, Zn superoxide dismutase: not only a dismutase enzyme. Front Physiol 7:594. 10.3389/fphys.2016.00594 PubMed PMC

Monserrat-Mesquida M, Quetglas-Llabrés M, Abbate M et al (2020) Oxidative stress and pro-inflammatory status in patients with non-alcoholic fatty liver disease. Antioxidants (Basel). 10.3390/antiox9080759 PubMed PMC

Moya D, Baker SS, Liu W et al (2015) Novel pathway for iron deficiency in pediatric non-alcoholic steatohepatitis. Clin Nutr 34(3):549–556. 10.1016/j.clnu.2014.06.011 PubMed

Murakami S, Ono A, Kawasaki A, Takenaga T, Ito T (2018) Taurine attenuates the development of hepatic steatosis through the inhibition of oxidative stress in a model of nonalcoholic fatty liver disease in vivo and in vitro. Amino Acids 50(9):1279–1288. 10.1007/s00726-018-2605-8 PubMed

Musso G, Gambino R, De Michieli F et al (2007) Nitrosative stress predicts the presence and severity of nonalcoholic fatty liver at different stages of the development of insulin resistance and metabolic syndrome: possible role of vitamin A intake. Am J Clin Nutr 86(3):661–671. 10.1093/ajcn/86.3.661 PubMed

Nagaya T, Tanaka N, Kimura T et al (2015) Mechanism of the development of nonalcoholic steatohepatitis after pancreaticoduodenectomy. BBA Clin 3:168–174. 10.1016/j.bbacli.2015.02.001 PubMed PMC

Nam H, Lim JH, Kim TW et al (2023) Extracellular superoxide dismutase attenuates hepatic oxidative stress in nonalcoholic fatty liver disease through the adenosine monophosphate-activated protein kinase activation. Antioxidants (Basel). 10.3390/antiox12122040 PubMed PMC

Namikawa C, Shu-Ping Z, Vyselaar JR et al (2004) Polymorphisms of microsomal triglyceride transfer protein gene and manganese superoxide dismutase gene in non-alcoholic steatohepatitis. J Hepatol 40(5):781–786. 10.1016/j.jhep.2004.01.028 PubMed

Nan YM, Wu WJ, Fu N et al (2009) Antioxidants vitamin E and 1-aminobenzotriazole prevent experimental non-alcoholic steatohepatitis in mice. Scand J Gastroenterol 44(9):1121–1131. 10.1080/00365520903114912 PubMed

Nayan SI, Chowdhury FI, Akter N et al (2021) Leaf powder supplementation of Senna alexandrina ameliorates oxidative stress, inflammation, and hepatic steatosis in high-fat diet-fed obese rats. PLoS ONE 16(4):e0250261. 10.1371/journal.pone.0250261 PubMed PMC

Nevzorova YA, Boyer-Diaz Z, Cubero FJ, Gracia-Sancho J (2020) Animal models for liver disease—a practical approach for translational research. J Hepatol 73(2):423–440. 10.1016/j.jhep.2020.04.011 PubMed

Nobili V, Pastore A, Gaeta LM et al (2005) Glutathione metabolism and antioxidant enzymes in patients affected by nonalcoholic steatohepatitis. Clin Chim Acta 355(1–2):105–111. 10.1016/j.cccn.2004.12.022 PubMed

Noeman SA, Hamooda HE, Baalash AA (2011) Biochemical study of oxidative stress markers in the liver, kidney and heart of high fat diet induced obesity in rats. Diabetol Metab Syndr 3(1):17. 10.1186/1758-5996-3-17 PubMed PMC

Nor Azman NHE, Goon JA, Abdul Ghani SM, Hamid Z, Wan Ngah WZ (2018) Comparing palm oil tocotrienol-rich fraction and α-tocopherol supplementation on the antioxidant levels of older adults. Antioxidants (Basel). 10.3390/antiox7060074 PubMed PMC

Nosrati N, Aghazadeh S, Yazdanparast R (2010) Effects of Teucrium polium on Insulin Resistance in Nonalcoholic Steatohepatitis. J Acupunct Meridian Stud 3(2):104–110. 10.1016/s2005-2901(10)60019-2 PubMed

Nunes-Souza V, César-Gomes CJ, Da Fonseca LJ, Guedes Gda S, Smaniotto S, Rabelo LA (2016) Aging increases susceptibility to high fat diet-induced metabolic syndrome in C57BL/6 mice: improvement in glycemic and lipid profile after antioxidant therapy. Oxid Med Cell Longev 2016:1987960. 10.1155/2016/1987960 PubMed PMC

Oniki K, Hori M, Saruwatari J et al (2013) Interactive effects of smoking and glutathione S-transferase polymorphisms on the development of non-alcoholic fatty liver disease. Toxicol Lett 220(2):143–149. 10.1016/j.toxlet.2013.04.019 PubMed

Ortenzi VH, Oliveira AC, Vasconcelos RP et al (2024) High-fat diet elicits sex-based differences in liver inflammatory cytokines and redox homeostasis. Appl Physiol Nutr Metab 49(8):1083–1092. 10.1139/apnm-2023-0457 PubMed

Pacana T, Cazanave S, Verdianelli A et al (2015) Dysregulated hepatic methionine metabolism drives homocysteine elevation in diet-induced nonalcoholic fatty liver disease. PLoS ONE 10(8):e0136822. 10.1371/journal.pone.0136822 PubMed PMC

Pacana T, Sanyal AJ (2012) Vitamin E and nonalcoholic fatty liver disease. Curr Opin Clin Nutr Metab Care 15(6):641–648. 10.1097/MCO.0b013e328357f747 PubMed PMC

Pan M, Deng Y, Qiu Y et al (2024) Shenling Baizhu powder alleviates non-alcoholic fatty liver disease by modulating autophagy and energy metabolism in high-fat diet-induced rats. Phytomedicine 130:155712. 10.1016/j.phymed.2024.155712 PubMed

Park HS, Jang JE, Ko MS et al (2016) Statins increase mitochondrial and peroxisomal fatty acid oxidation in the liver and prevent non-alcoholic steatohepatitis in mice. Diabetes Metab J 40(5):376–385. 10.4093/dmj.2016.40.5.376 PubMed PMC

Patel V, Edison P (2024) Cardiometabolic risk factors and neurodegeneration: a review of the mechanisms underlying diabetes, obesity and hypertension in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 95(6):581–589. 10.1136/jnnp-2023-332661 PubMed PMC

Pereira E, Silvares RR, Flores EEI et al (2017) Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease. PLoS ONE 12(6):e0179654. 10.1371/journal.pone.0179654 PubMed PMC

Perlemuter G, Davit-Spraul A, Cosson C et al (2005) Increase in liver antioxidant enzyme activities in non-alcoholic fatty liver disease. Liver Int 25(5):946–953. 10.1111/j.1478-3231.2005.01126.x PubMed

Perumpail BJ, Khan MA, Yoo ER, Cholankeril G, Kim D, Ahmed A (2017) Clinical epidemiology and disease burden of nonalcoholic fatty liver disease. World J Gastroenterol 23(47):8263–8276. 10.3748/wjg.v23.i47.8263 PubMed PMC

Perumpail BJ, Li AA, John N et al (2018) The role of vitamin E in the treatment of NAFLD. Diseases. 10.3390/diseases6040086 PubMed PMC

Phung N, Pera N, Farrell G, Leclercq I, Hou JY, George J (2009) Pro-oxidant-mediated hepatic fibrosis and effects of antioxidant intervention in murine dietary steatohepatitis. Int J Mol Med 24(2):171–180. 10.3892/ijmm_00000220 PubMed

Podszun MC, Frank J (2021) Impact of vitamin E on redox biomarkers in non-alcoholic fatty liver disease. Redox Biol 42:101937. 10.1016/j.redox.2021.101937 PubMed PMC

Podszun MC, Grebenstein N, Spruss A et al (2014) Dietary α-tocopherol and atorvastatin reduce high-fat-induced lipid accumulation and down-regulate CD36 protein in the liver of guinea pigs. J Nutr Biochem 25(5):573–579. 10.1016/j.jnutbio.2014.01.008 PubMed

Post A, Garcia E, van den Berg EH et al (2021) Nonalcoholic fatty liver disease, circulating ketone bodies and all-cause mortality in a general population-based cohort. Eur J Clin Invest 51(12):e13627. 10.1111/eci.13627 PubMed PMC

Prasun P, Ginevic I, Oishi K (2021) Mitochondrial dysfunction in nonalcoholic fatty liver disease and alcohol related liver disease. Transl Gastroenterol Hepatol 6:4. 10.21037/tgh-20-125 PubMed PMC

Prysyazhnyuk V, Sydorchuk L, Sydorchuk R et al (2021) Glutathione-S-transferases genes-promising predictors of hepatic dysfunction. World J Hepatol 13(6):620–633. 10.4254/wjh.v13.i6.620 PubMed PMC

Ramanathan R, Ali AH, Ibdah JA (2022) Mitochondrial Dysfunction plays central role in nonalcoholic fatty liver disease. Int J Mol Sci. 10.3390/ijms23137280 PubMed PMC

Ramírez-Mejía MM, Jiménez-Gutiérrez C, Eslam M, George J, Méndez-Sánchez N (2024) Breaking new ground: MASLD vs MAFLD-which holds the key for risk stratification? Hepatol Int 18(1):168–178. 10.1007/s12072-023-10620-y PubMed

Ramos MJ, Bandiera L, Menolascina F, Fallowfield JA (2022) In vitro models for non-alcoholic fatty liver disease: Emerging platforms and their applications. iScience 25(1):103549. 10.1016/j.isci.2021.103549 PubMed PMC

Reiniers MJ, van Golen RF, van Gulik TM, Heger M (2014) Reactive oxygen and nitrogen species in steatotic hepatocytes: a molecular perspective on the pathophysiology of ischemia-reperfusion injury in the fatty liver. Antioxid Redox Signal 21(7):1119–1142. 10.1089/ars.2013.5486 PubMed PMC

Rinella ME, Neuschwander-Tetri BA, Siddiqui MS et al (2023) AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 10.1097/HEP.0000000000000323 PubMed PMC

Rodriguez-Ramiro I, Pastor-Fernandez A, Lopez-Aceituno JL et al (2024) Pharmacological and genetic increases in liver NADPH levels ameliorate NASH progression in female mice. Free Radical Biol Med 210:448–461. 10.1016/j.freeradbiomed.2023.11.019 PubMed

Rosas-Campos R, Sandoval-Rodriguez AS, Rodriguez-Sanabria JS et al (2024) A novel foodstuff mixture improves the gut-liver axis in masld mice and the gut microbiota in overweight/obese patients. Antioxidants (Basel). 10.3390/antiox13060664 PubMed PMC

Ross D, Siegel D (2021) The diverse functionality of NQO1 and its roles in redox control. Redox Biol 41:101950. 10.1016/j.redox.2021.101950 PubMed PMC

Santamaria E, Avila MA, Latasa MU et al (2003) Functional proteomics of nonalcoholic steatohepatitis: mitochondrial proteins as targets of S-adenosylmethionine. Proc Natl Acad Sci USA 100(6):3065–3070. 10.1073/pnas.0536625100 PubMed PMC

Santos-López JA, Garcimartín A, Merino P et al (2016) Effects of silicon vs. hydroxytyrosol-enriched restructured pork on liver oxidation status of aged rats fed high-saturated/high-cholesterol diets. PLoS One 11(1):e0147469. 10.1371/journal.pone.0147469 PubMed PMC

Sanyal AJ, Campbell-Sargent C, Mirshahi F et al (2001) Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 120(5):1183–1192. 10.1053/gast.2001.23256 PubMed

Schattenberg JM, Wang Y, Singh R, Rigoli RM, Czaja MJ (2005) Hepatocyte CYP2E1 overexpression and steatohepatitis lead to impaired hepatic insulin signaling. J Biol Chem 280(11):9887–9894. 10.1074/jbc.M410310200 PubMed

Seven A, Guzel S, Seymen O et al (2004) Effects of vitamin E supplementation on oxidative stress in streptozotocin induced diabetic rats: investigation of liver and plasma. Yonsei Med J 45(4):703–710. 10.3349/ymj.2004.45.4.703 PubMed

Sharma A, Anand SK, Singh N, Dwivedi UN, Kakkar P (2020) Berbamine induced AMPK activation regulates mTOR/SREBP-1c axis and Nrf2/ARE pathway to allay lipid accumulation and oxidative stress in steatotic HepG2 cells. Eur J Pharmacol 882:173244. 10.1016/j.ejphar.2020.173244 PubMed

Shearn CT, Saba LM, Roede JR, Orlicky DJ, Shearn AH, Petersen DR (2017) Differential carbonylation of proteins in end-stage human fatty and nonfatty NASH. Free Radical Biol Med 113:280–290. 10.1016/j.freeradbiomed.2017.10.004 PubMed PMC

Shin SK, Cho HW, Song SE, Song DK (2018) Catalase and nonalcoholic fatty liver disease. Pflugers Arch 470(12):1721–1737. 10.1007/s00424-018-2195-z PubMed

Silja K, Selvaganabathy N, Kalaiselvi T, Thirunavukkarasu C (2023) Inhibition of glutathione generation in hepatic steatotic rats augments oxidative stress. Toxicol Mech Methods 33(7):596–606. 10.1080/15376516.2023.2202784 PubMed

Song L, Qu D, Zhang Q et al (2017) Phytosterol esters attenuate hepatic steatosis in rats with non-alcoholic fatty liver disease rats fed a high-fat diet. Sci Rep 7:41604. 10.1038/srep41604 PubMed PMC

Sreekumar R, Rosado B, Rasmussen D, Charlton M (2003) Hepatic gene expression in histologically progressive nonalcoholic steatohepatitis. Hepatology 38(1):244–251. 10.1053/jhep.2003.50290 PubMed

Stefano JT, Pereira IV, Torres MM et al (2015) Sorafenib prevents liver fibrosis in a non-alcoholic steatohepatitis (NASH) rodent model. Braz J Med Biol Res 48(5):408–414. 10.1590/1414-431x20143962 PubMed PMC

Su H, Li Y, Hu D et al (2018) Procyanidin B2 ameliorates free fatty acids-induced hepatic steatosis through regulating TFEB-mediated lysosomal pathway and redox state. Free Radic Biol Med 126:269–286. 10.1016/j.freeradbiomed.2018.08.024 PubMed

Svegliati-Baroni G, Pierantonelli I, Torquato P et al (2019) Lipidomic biomarkers and mechanisms of lipotoxicity in non-alcoholic fatty liver disease. Free Radic Biol Med 144:293–309. 10.1016/j.freeradbiomed.2019.05.029 PubMed

Svoboda DS, Kawaja MD (2012) Changes in hepatic protein expression in spontaneously hypertensive rats suggest early stages of non-alcoholic fatty liver disease. J Proteomics 75(6):1752–1763. 10.1016/j.jprot.2011.12.011 PubMed

Świderska M, Maciejczyk M, Zalewska A, Pogorzelska J, Flisiak R, Chabowski A (2019) Oxidative stress biomarkers in the serum and plasma of patients with non-alcoholic fatty liver disease (NAFLD) Can plasma AGE be a marker of NAFLD? Oxidative stress biomarkers in NAFLD patients. Free Radic Res 53(8):841–850. 10.1080/10715762.2019.1635691 PubMed

Szarka A, Tomasskovics B, Banhegyi G (2012) The ascorbate-glutathione-alpha-tocopherol triad in abiotic stress response. Int J Mol Sci 13(4):4458–4483. 10.3390/ijms13044458 PubMed PMC

Tabei SM, Fakher S, Djalali M et al (2015) Effect of vitamins A, E, C and omega-3 fatty acids supplementation on the level of catalase and superoxide dismutase activities in streptozotocin-induced diabetic rats. Bratisl Lek Listy 116(2):115–118. 10.4149/bll_2015_022 PubMed

Tanaka K, Masaki Y, Tanaka M et al (2014) Exenatide improves hepatic steatosis by enhancing lipid use in adipose tissue in nondiabetic rats. World J Gastroenterol 20(10):2653–2663. 10.3748/wjg.v20.i10.2653 PubMed PMC

Thomàs-Moyà E, Gómez-Pérez Y, Fiol M, Gianotti M, Lladó I, Proenza AM (2008) Gender related differences in paraoxonase 1 response to high-fat diet-induced oxidative stress. Obesity 16(10):2232–2238. 10.1038/oby.2008.340 PubMed

Tsai SY, Chung PC, Owaga EE et al (2016) Alpha-mangostin from mangosteen (Garcinia mangostana Linn.) pericarp extract reduces high fat-diet induced hepatic steatosis in rats by regulating mitochondria function and apoptosis. Nutr Metab (Lond) 13:88. 10.1186/s12986-016-0148-0 PubMed PMC

Tsang CK, Liu Y, Thomas J, Zhang Y, Zheng XF (2014) Superoxide dismutase 1 acts as a nuclear transcription factor to regulate oxidative stress resistance. Nat Commun 5:3446. 10.1038/ncomms4446 PubMed PMC

Tsuchida T, Lee YA, Fujiwara N et al (2018) A simple diet- and chemical-induced murine NASH model with rapid progression of steatohepatitis, fibrosis and liver cancer. J Hepatol 69(2):385–395. 10.1016/j.jhep.2018.03.011 PubMed PMC

Vacca M, Kamzolas I, Harder LM et al (2024) An unbiased ranking of murine dietary models based on their proximity to human metabolic dysfunction-associated steatotic liver disease (MASLD). Nat Metab 6(6):1178–1196. 10.1038/s42255-024-01043-6 PubMed PMC

Valdecantos MP, Pérez-Matute P, González-Muniesa P, Prieto-Hontoria PL, Moreno-Aliaga MJ, Martínez JA (2012) Lipoic acid improves mitochondrial function in nonalcoholic steatosis through the stimulation of sirtuin 1 and sirtuin 3. Obesity 20(10):1974–1983. 10.1038/oby.2012.32 PubMed

Valenzuela R, Echeverria F, Ortiz M et al (2017) Hydroxytyrosol prevents reduction in liver activity of Δ-5 and Δ-6 desaturases, oxidative stress, and depletion in long chain polyunsaturated fatty acid content in different tissues of high-fat diet fed mice. Lipids Health Dis 16(1):64. 10.1186/s12944-017-0450-5 PubMed PMC

Valenzuela R, Rincón-Cervera M, Echeverría F et al (2018) Iron-induced pro-oxidant and pro-lipogenic responses in relation to impaired synthesis and accretion of long-chain polyunsaturated fatty acids in rat hepatic and extrahepatic tissues. Nutrition 45:49–58. 10.1016/j.nut.2017.07.007 PubMed

Vecchione G, Grasselli E, Voci A et al (2016) Silybin counteracts lipid excess and oxidative stress in cultured steatotic hepatic cells. World J Gastroenterol 22(26):6016–6026. 10.3748/wjg.v22.i26.6016 PubMed PMC

Veeramani C, Alsaif MA, Al-Numair KS (2017) Lavatera critica, a green leafy vegetable, controls high fat diet induced hepatic lipid accumulation and oxidative stress through the regulation of lipogenesis and lipolysis genes. Biomed Pharmacother 96:1349–1357. 10.1016/j.biopha.2017.11.072 PubMed

Venancio-Brochi JC, Pereira LM, Calil FA et al (2021) Glutathione reductase: a cytoplasmic antioxidant enzyme and a potential target for phenothiazinium dyes in Neospora caninum. Int J Biol Macromol 187:964–975. 10.1016/j.ijbiomac.2021.07.108 PubMed

Videla LA, Rodrigo R, Orellana M et al (2004) Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients. Clin Sci (Lond) 106(3):261–268. 10.1042/cs20030285 PubMed

Vornoli A, Pozzo L, Della Croce CM, Gervasi PG, Longo V (2014) Drug metabolism enzymes in a steatotic model of rat treated with a high fat diet and a low dose of streptozotocin. Food Chem Toxicol 70:54–60. 10.1016/j.fct.2014.04.042 PubMed

Wan YY, Cai Y, Li J et al (2001) Regulation of peroxisome proliferator activated receptor alpha-mediated pathways in alcohol fed cytochrome P450 2E1 deficient mice. Hepatol Res 19(2):117–130. 10.1016/s1386-6346(00)00089-9 PubMed

Wang Y, Ausman LM, Greenberg AS, Russell RM, Wang XD (2009) Nonalcoholic steatohepatitis induced by a high-fat diet promotes diethylnitrosamine-initiated early hepatocarcinogenesis in rats. Int J Cancer 124(3):540–546. 10.1002/ijc.23995 PubMed PMC

Wang Y, Chen J, Kong W et al (2017) Regulation of SIRT3/FOXO1 signaling pathway in rats with non-alcoholic steatohepatitis by salvianolic acid B. Arch Med Res 48(6):506–512. 10.1016/j.arcmed.2017.11.016 PubMed

Wang DJ, Cai YQ, Pan SZ et al (2018) Effect of total flavone of haw leaves on nuclear factor erythroid-2 related factor and other related factors in nonalcoholic steatohepatitis rats. Chin J Integr Med 24(4):265–271. 10.1007/s11655-016-2450-0 PubMed

Wang SX, Yan JS, Chan YS (2022) Advancements in MAFLD Modeling with Human Cell and Organoid Models. Int J Mol Sci. 10.3390/ijms231911850 PubMed PMC

Wasef L, Nassar AMK, El-Sayed YS et al (2021) The potential ameliorative impacts of cerium oxide nanoparticles against fipronil-induced hepatic steatosis. Sci Rep 11(1):1310. 10.1038/s41598-020-79479-5 PubMed PMC

Wat E, Ng CF, Wong EC et al (2016) The hepatoprotective effect of the combination use of Fructus Schisandrae with statin–a preclinical evaluation. J Ethnopharmacol 178:104–114. 10.1016/j.jep.2015.12.004 PubMed

Wu D, Zheng N, Qi K et al (2015) Exogenous hydrogen sulfide mitigates the fatty liver in obese mice through improving lipid metabolism and antioxidant potential. Med Gas Res 5(1):1. 10.1186/s13618-014-0022-y PubMed PMC

Wu PJ, Chen JB, Lee WC et al (2018) Oxidative stress and nonalcoholic fatty liver disease in hemodialysis patients. Biomed Res Int 2018:3961748. 10.1155/2018/3961748 PubMed PMC

Xia SF, Le GW, Wang P, Qiu YY, Jiang YY, Tang X (2016) Regressive effect of myricetin on hepatic steatosis in mice fed a high-fat diet. Nutrients. 10.3390/nu8120799 PubMed PMC

Xia SF, Shao J, Zhao SY et al (2018) Niga-ichigoside F1 ameliorates high-fat diet-induced hepatic steatosis in male mice by Nrf2 activation. Food Funct 9(2):906–916. 10.1039/c7fo01051f PubMed

Xie K, He X, Chen K, Sakao K, Hou DX (2020) Ameliorative effects and molecular mechanisms of vine tea on western diet-induced NAFLD. Food Funct 11(7):5976–5991. 10.1039/d0fo00795a PubMed

Xu J, Wang X, Cao K, Dong Z, Feng Z, Liu J (2017) Combination of β-glucan and Morus alba L. Leaf Extract Promotes Metabolic Benefits in Mice Fed a High-Fat Diet. Nutrients. 10.3390/nu9101110 PubMed PMC

Xu X, Sun S, Liang L et al (2021) Role of the aryl hydrocarbon receptor and gut microbiota-derived metabolites indole-3-acetic acid in sulforaphane alleviates hepatic steatosis in mice. Front Nutr 8:756565. 10.3389/fnut.2021.756565 PubMed PMC

Yang ZR, Wang HF, Zuo TC, Guan LL, Dai N (2016) Salidroside alleviates oxidative stress in the liver with non- alcoholic steatohepatitis in rats. BMC Pharmacol Toxicol 17:16. 10.1186/s40360-016-0059-8 PubMed PMC

Ye J, Tian X, Wang Q et al (2022) Monkfish peptides mitigate high fat diet-induced hepatic steatosis in mice. Mar Drugs. 10.3390/md20050312 PubMed PMC

Ye Q, Jiang Y, Wu D et al (2023) Atractylodin alleviates nonalcoholic fatty liver disease by regulating Nrf2-mediated ferroptosis. Heliyon 9(7):e18321. 10.1016/j.heliyon.2023.e18321 PubMed PMC

Yesilova Z, Yaman H, Oktenli C et al (2005) Systemic markers of lipid peroxidation and antioxidants in patients with nonalcoholic Fatty liver disease. Am J Gastroenterol 100(4):850–855. 10.1111/j.1572-0241.2005.41500.x PubMed

Yoshioka S, Hamada A, Jobu K et al (2010) Effects of Eriobotrya japonica seed extract on oxidative stress in rats with non-alcoholic steatohepatitis. J Pharm Pharmacol 62(2):241–246. 10.1211/jpp.62.02.0012 PubMed

Younossi ZM, Baranova A, Ziegler K et al (2005) A genomic and proteomic study of the spectrum of nonalcoholic fatty liver disease. Hepatology 42(3):665–674. 10.1002/hep.20838 PubMed

Yu Q, Lee YY, Xia ZY, Liong EC, Xiao J, Tipoe GL (2021) S-allylmercaptocysteine improves nonalcoholic steatohepatitis by enhancing AHR/NRF2-mediated drug metabolising enzymes and reducing NF-κB/IκBα and NLRP3/6-mediated inflammation. Eur J Nutr 60(2):961–973. 10.1007/s00394-020-02305-1 PubMed

Zakaria Z, Othman ZA, Suleiman JB et al (2021) Hepatoprotective effect of bee bread in metabolic dysfunction-associated fatty liver disease (mafld) rats: impact on oxidative stress and inflammation. Antioxidants (Basel). 10.3390/antiox10122031 PubMed PMC

Zelko IN, Mariani TJ, Folz RJ (2002) Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radical Biol Med 33(3):337–349. 10.1016/s0891-5849(02)00905-x PubMed

Zhang CX, Guo LK, Qin YM, Li GY (2015) Interaction of Polymorphisms of Resistin Gene Promoter -420C/G, Glutathione Peroxidase -1 Gene Pro198Leu and Cigarette Smoking in Nonalcoholic Fatty Liver Disease. Chin Med J (Engl) 128(18):2467–2473. 10.4103/0366-6999.164931 PubMed PMC

Zhang CX, Guo LK, Qin YM, Li GY (2016) Association of polymorphisms of adiponectin gene promoter-11377C/G, glutathione peroxidase-1 gene C594T, and cigarette smoking in nonalcoholic fatty liver disease. J Chin Med Assoc 79(4):195–204. 10.1016/j.jcma.2015.09.003 PubMed

Zhang K, Chen D, Ma K, Wu X, Hao H, Jiang S (2018a) NAD(P)H: quinone oxidoreductase 1 (NQO1) as a therapeutic and diagnostic target in cancer. J Med Chem 61(16):6983–7003. 10.1021/acs.jmedchem.8b00124 PubMed

Zhang X, Ji R, Sun H et al (2018b) Scutellarin ameliorates nonalcoholic fatty liver disease through the PPARγ/PGC-1α-Nrf2 pathway. Free Radic Res 52(2):198–211. 10.1080/10715762.2017.1422602 PubMed

Zhang T, Wang MY, Wang GD et al (2024) Metformin improves nonalcoholic fatty liver disease in db/db mice by inhibiting ferroptosis. Eur J Pharmacol 966:176341. 10.1016/j.ejphar.2024.176341 PubMed

Zhao MG, Sheng XP, Huang YP et al (2018a) Triterpenic acids-enriched fraction from Cyclocarya paliurus attenuates non-alcoholic fatty liver disease via improving oxidative stress and mitochondrial dysfunction. Biomed Pharmacother 104:229–239. 10.1016/j.biopha.2018.03.170 PubMed

Zhao XJ, Yu HW, Yang YZ et al (2018b) Polydatin prevents fructose-induced liver inflammation and lipid deposition through increasing miR-200a to regulate Keap1/Nrf2 pathway. Redox Biol 18:124–137. 10.1016/j.redox.2018.07.002 PubMed PMC

Zheng W, Song Z, Li S, Hu M, Shaukat H, Qin H (2021) Protective effects of sesamol against liver oxidative stress and inflammation in high-fat diet-induced hepatic steatosis. Nutrients. 10.3390/nu13124484 PubMed PMC

Zhu CG, Liu YX, Wang H et al (2017) Active form of vitamin D ameliorates non-alcoholic fatty liver disease by alleviating oxidative stress in a high-fat diet rat model. Endocr J 64(7):663–673. 10.1507/endocrj.EJ16-0542 PubMed

Zhu Z, Hu R, Li J et al (2021) Alpinetin exerts anti-inflammatory, anti-oxidative and anti-angiogenic effects through activating the Nrf2 pathway and inhibiting NLRP3 pathway in carbon tetrachloride-induced liver fibrosis. Int Immunopharmacol 96:107660. 10.1016/j.intimp.2021.107660 PubMed

Zilu S, Qian H, Haibin W et al (2019) Effects of XIAP on high fat diet-induced hepatic steatosis: a mechanism involving NLRP3 inflammasome and oxidative stress. Aging (Albany NY) 11(24):12177–12201. 10.18632/aging.102559 PubMed PMC