The Role of Oxidative Stress in the Pathogenesis and Treatment of Alcoholic Fatty Liver Disease

Authors

  • Jingzhi Wan School of Public Health, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi, China
  • Aozhong Li School of Public Health, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi, China
  • Qilong Yang School of Public Health, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi, China
  • Dilinuer Xieraili Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, Shaanxi, China
  • Huijie Ran Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, Shaanxi, China
  • Ruijie Bai School of Public Health, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi, China
  • Qiling Liu School of Public Health, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi, China
  • Xujun Qin Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, Shaanxi, China

DOI:

https://doi.org/10.53469/jcmp.2025.07(03).42

Keywords:

Alcoholic Fatty Liver Disease (AFLD), Oxidative Stress, Antioxidant, Pathogenesis, Therapeutic Strategy

Abstract

Alcoholic fatty liver disease (AFLD) is a complex hepatic condition characterized by the accumulation of triglyceride in the liver due to excessive alcohol consumption. Currently the pathogenesis of ALD is not fully understood. Oxidative stress is an imbalance between the production of reactive oxygen species (ROS) and the antioxidant defenses. Recent studies highlight the critical role of oxidative stress in the pathogenesis of AFLD, suggesting that it is a primary mechanism underlying liver injury in AFLD. This review summarizes mechanisms by which oxidative stress contributes to the pathogenesis of AFLD, including apoptosis, necrosis, ferroptosis, and autophagy. It also explores potential therapeutic strategies for treating AFLD based on the critical role of oxidative stress. By delving into the intricate relationship between oxidative stress and hepatic steatosis, this review seeks to provide new insights for the prevention and treatment of AFLD.

References

A.C.S. Rabelo, A.K.L. Andrade, D.C. Costa, The Role of Oxidative Stress in Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Preclinical Studies, Nutrients 16(8) (2024) 1174.

H.K. Seitz, R. Bataller, H. Cortez-Pinto, B. Gao, A. Gual, C. Lackner, P. Mathurin, S. Mueller, G. Szabo, H. Tsukamoto, Alcoholic liver disease, Nat Rev Dis Primers 4(1) (2018) 16.

H.K. Seitz, B. Moreira, M.G. Neuman, Pathogenesis of Alcoholic Fatty Liver a Narrative Review, Life (Basel) 13(8) (2023) 1662.

A. Allameh, R. Niayesh-Mehr, A. Aliarab, G. Sebastiani, K. Pantopoulos, Oxidative Stress in Liver Pathophysiology and Disease, Antioxidants (Basel) 12(9) (2023) 1653.

N. Sadasivam, Y.J. Kim, K. Radhakrishnan, D.K. Kim, Oxidative Stress, Genomic Integrity, and Liver Diseases, Molecules 27(10) (2022) 3159.

Y. Jiang, L. Xu, X. Zhu, X. Zhu, X. Xu, J. Li, Hyperglycemic stress induces oxidative damage of enteric glial cells by triggering redoxosomes/p66SHC activation, Redox Rep 29(1) (2024) 2324234.

Y. Long, H. Shi, J. Ye, X. Qi, Exploring Strategies to Prevent and Treat Ovarian Cancer in Terms of Oxidative Stress and Antioxidants, Antioxidants (Basel) 14(1) (2025) 114.

A.C. Martins, G.H. Oliveira-Paula, A.A. Tinkov, A.V. Skalny, Y. Tizabi, A.B. Bowman, M. Aschner, Role of manganese in brain health and disease: Focus on oxidative stress, Free Radic Biol Med 232 (2025) 306-318.

E.A.M. Saleh, F. Al-Dolaimy, Y. Qasim Almajidi, S. Baymakov, M.M. Kader, M.I. Ullah, A.H.R. Abbas, I.H. Khlewee, Y.S. Bisht, A.H. Alsaalamy, Oxidative stress affects the beginning of the growth of cancer cells through a variety of routes, Pathol Res Pract 249 (2023) 154664.

U.C. Dash, N.K. Bhol, S.K. Swain, R.R. Samal, P.K. Nayak, V. Raina, S.K. Panda, R.G. Kerry, A.K. Duttaroy, A.B. Jena, Oxidative stress and inflammation in the pathogenesis of neurological disorders: Mechanisms and implications, Acta Pharm Sin B 15(1) (2025) 15-34.

S.P. Tang, X.L. Mao, Y.H. Chen, L.L. Yan, L.P. Ye, S.W. Li, Reactive Oxygen Species Induce Fatty Liver and Ischemia-Reperfusion Injury by Promoting Inflammation and Cell Death, Front Immunol 13 (2022) 870239.

D.N. Daraghmeh, R. Karaman, The Redox Process in Red Blood Cells: Balancing Oxidants and Antioxidants, Antioxidants (Basel) 14(1) (2024) 36.

M.M. Sikder, X. Li, S. Akumwami, S.A. Labony, Reactive Oxygen Species: Role in Pathophysiology, and Mechanism of Endogenous and Dietary Antioxidants during Oxidative Stress, Chonnam Med J 61(1) (2025) 32-45.

T. Kalogerakou, M. Antoniadou, The Role of Dietary Antioxidants, Food Supplements and Functional Foods for Energy Enhancement in Healthcare Professionals, Antioxidants (Basel) 13(12) (2024) 1508.

V. Subramaniyan, S. Chakravarthi, R. Jegasothy, W.Y. Seng, N.K. Fuloria, S. Fuloria, I. Hazarika, A. Das, Alcohol-associated liver disease: A review on its pathophysiology, diagnosis and drug therapy, Toxicol Rep 8 (2021) 376-385.

M. Dukic, T. Radonjic, I. Jovanovic, M. Zdravkovic, Z. Todorovic, N. Kraisnik, B. Arandelovic, O. Mandic, V. Popadic, N. Nikolic, S. Klasnja, A. Manojlovic, A. Divac, J. Gacic, M. Brajkovic, S. Opric, M. Popovic, M. Brankovic, Alcohol, Inflammation, and Microbiota in Alcoholic Liver Disease, Int J Mol Sci 24(4) (2023) 3735.

W. Lai, J. Zhang, J. Sun, T. Min, Y. Bai, J. He, H. Cao, Q. Che, J. Guo, Z. Su, Oxidative stress in alcoholic liver disease, focusing on proteins, nucleic acids, and lipids: A review, Int J Biol Macromol 278(Pt 3) (2024) 134809.

A. Adameova, C. Horvath, S. Abdul-Ghani, Z.V. Varga, M.S. Suleiman, N.S. Dhalla, Interplay of Oxidative Stress and Necrosis-like Cell Death in Cardiac Ischemia/Reperfusion Injury: A Focus on Necroptosis, Biomedicines 10(1) (2022) 127.

J. Liu, Ethanol and liver: recent insights into the mechanisms of ethanol-induced fatty liver, World J Gastroenterol 20(40) (2014) 14672-85.

H. Gao, Y. Jiang, G. Zeng, N. Huda, T. Thoudam, Z. Yang, S. Liangpunsakul, J. Ma, Cell-to-cell and organ-to-organ crosstalk in the pathogenesis of alcohol-associated liver disease, eGastroenterology 2(4) (2024) 100104.

T. Behl, R. Makkar, A. Sehgal, S. Singh, N. Sharma, G. Zengin, S. Bungau, F.L. Andronie-Cioara, M.A. Munteanu, M.C. Brisc, D. Uivarosan, C. Brisc, Current Trends in Neurodegeneration: Cross Talks between Oxidative Stress, Cell Death, and Inflammation, Int J Mol Sci 22(14) (2021) 7432.

S. Sifuentes-Franco, D.E. Padilla-Tejeda, S. Carrillo-Ibarra, A.G. Miranda-Diaz, Oxidative Stress, Apoptosis, and Mitochondrial Function in Diabetic Nephropathy, Int J Endocrinol 2018 (2018) 1875870.

L. Petagine, M.G. Zariwala, S. Somavarapu, S.H.Y. Chan, E.A. Kaya, V.B. Patel, Oxidative stress in a cellular model of alcohol-related liver disease: protection using curcumin nanoformulations, Sci Rep 15(1) (2025) 7752.

N. Subramaiyam, Insights of mitochondrial involvement in alcoholic fatty liver disease, J Cell Physiol 238(10) (2023) 2175-2190.

Y. He, Y. Lin, J. Song, M. Song, X. Nie, H. Sun, C. Xu, Z. Han, J. Cai, From mechanisms to medicine: Ferroptosis as a Therapeutic target in liver disorders, Cell Commun Signal 23(1) (2025) 125.

J.F. Shi, Y. Liu, Y. Wang, R. Gao, Y. Wang, J. Liu, Targeting ferroptosis, a novel programmed cell death, for the potential of alcohol-related liver disease therapy, Front Pharmacol 14 (2023) 1194343.

X.D. Zhang, Z.Y. Liu, M.S. Wang, Y.X. Guo, X.K. Wang, K. Luo, S. Huang, R.F. Li, Mechanisms and regulations of ferroptosis, Front Immunol 14 (2023) 1269451.

J.Q. Bo, Z.P. Guo, Y.H. Han, L.X. Liu, Advancements in ferroptosis research and therapeutic strategies for alcoholic liver disease: a narrative review, Eur Rev Med Pharmacol Sci 27(19) (2023) 9296-9308.

Z. Zhou, T.J. Ye, E. DeCaro, B. Buehler, Z. Stahl, G. Bonavita, M. Daniels, M. You, Intestinal SIRT1 Deficiency Protects Mice from Ethanol-Induced Liver Injury by Mitigating Ferroptosis, Am J Pathol 190(1) (2020) 82-92.

J. Luo, G. Song, N. Chen, M. Xie, X. Niu, S. Zhou, Y. Ji, X. Zhu, W. Ma, Q. Zhang, D. Yu, Ferroptosis contributes to ethanol-induced hepatic cell death via labile iron accumulation and GPx4 inactivation, Cell Death Discov 9(1) (2023) 311.

T.V. Le, N.H. Truong, A.X.L. Holterman, Autophagy modulates physiologic and adaptive response in the liver, Liver Res 7(4) (2023) 304-320.

D. Salete-Granado, C. Carbonell, D. Puertas-Miranda, V.J. Vega-Rodriguez, M. Garcia-Macia, A.B. Herrero, M. Marcos, Autophagy, Oxidative Stress, and Alcoholic Liver Disease: A Systematic Review and Potential Clinical Applications, Antioxidants (Basel) 12(7) (2023) 1425.

Y. Filali-Mouncef, C. Hunter, F. Roccio, S. Zagkou, N. Dupont, C. Primard, T. Proikas-Cezanne, F. Reggiori, The menage a trois of autophagy, lipid droplets and liver disease, Autophagy 18(1) (2022) 50-72.

X. Zhao, X. Xue, J. Wang, S. Dai, C. Peng, Y. Li, Quercetin alleviates ethanol-induced hepatic steatosis in L02 cells by activating TFEB translocation to compensate for inadequate autophagy, Phytother Res 37(1) (2023) 62-76.

L. Chen, Q. Liu, X. Li, L. Zhang, W. Dong, Q. Li, H. Su, G. Luo, Y. Huang, X. Yang, The diabetes medication Canagliflozin attenuates alcoholic liver disease by reducing hepatic lipid accumulation via SIRT1-AMPK-mTORC1 signaling pathway, Eur J Pharmacol 992 (2025) 177320.

S. Zheng, T. Xue, Q. Wang, P. Zhang, W. Qi, C. Xue, X. Li, H. Du, P. Zhang, X. Zao, Y. Ye, Chinese Medicine for the Treatment of Liver Cirrhosis: The Mechanism of Cellular Autophagy, Am J Chin Med 12 (2025) 1-25.

X. Wang, B. Liu, Y. Liu, Y. Wang, Z. Wang, Y. Song, J. Xu, C. Xue, Antioxidants ameliorate oxidative stress in alcoholic liver injury by modulating lipid metabolism and phospholipid homeostasis, Lipids 58(5) (2023) 229-240.

F. Chen, Z. Zhou, J. Fu, C. Gao, Selenomethionine Alleviates Alcohol-Induced Liver Injury by Inhibiting Ferroptosis, Dig Dis Sci (2025) 10.1007/s10620-025-08960-w.

T.A. Lin, B.J. Ke, S.C. Cheng, C.L. Lee, Red Quinoa Bran Extract Prevented Alcoholic Fatty Liver Disease via Increasing Antioxidative System and Repressing Fatty Acid Synthesis Factors in Mice Fed Alcohol Liquid Diet, Molecules 26(22) (2021) 6973.

K.H. Xu, D.F. Yang, M.Y. Liu, W. Xu, Y.H. Li, W.J. Xiao, Hepatoprotective effects and mechanisms of l-theanine and epigallocatechin gallate combined intervention in alcoholic fatty liver rats, J Sci Food Agric 104(13) (2024) 8230-8239.

J.S. Park, N. Rustamov, Y.S. Roh, The Roles of NFR2-Regulated Oxidative Stress and Mitochondrial Quality Control in Chronic Liver Diseases, Antioxidants (Basel) 12(11) (2023) 1928.

X. Zhao, L. Li, M. Zhou, M. Liu, Y. Deng, L. He, C. Guo, Y. Li, An Overview of the Mechanism of Penthorum chinense Pursh on Alcoholic Fatty Liver, Evid Based Complement Alternat Med 2020 (2020) 4875764.

R. Maslennikov, V. Ivashkin, I. Efremova, E. Poluektova, E. Shirokova, Probiotics in hepatology: An update, World J Hepatol 13(9) (2021) 1154-1166.

Downloads

Published

2025-03-28

How to Cite

Wan, J., Li, A., Yang, Q., Xieraili, D., Ran, H., Bai, R., … Qin, X. (2025). The Role of Oxidative Stress in the Pathogenesis and Treatment of Alcoholic Fatty Liver Disease. Journal of Contemporary Medical Practice, 7(3), 213–217. https://doi.org/10.53469/jcmp.2025.07(03).42

Issue

Vol. 7 No. 3 (2025): JCMP-Volume 7 Issue 3

Section

Articles

License

Copyright (c) 2025 Jingzhi Wan, Aozhong Li, Qilong Yang, Dilinuer Xieraili, Huijie Ran, Ruijie Bai, Qiling Liu, Xujun Qin

Creative Commons License

This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License.