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Review
. 2025 Jun 17;47(6):464.
doi: 10.3390/cimb47060464.

Reactive Oxygen Species as Key Molecules in the Pathogenesis of Alcoholic Fatty Liver Disease and Nonalcoholic Fatty Liver Disease: Future Perspectives

Zhiqing Zhang  1 , Hong Yang  1 , Fei Han  2 , Peng Guo  1
Affiliations
Review

Reactive Oxygen Species as Key Molecules in the Pathogenesis of Alcoholic Fatty Liver Disease and Nonalcoholic Fatty Liver Disease: Future Perspectives

Zhiqing Zhang et al. Curr Issues Mol Biol. .

Abstract

Reactive oxygen species (ROS) are central to the progression of alcoholic fatty liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD). In ALD, ROS arise from alcohol metabolism (CYP2E1 and ADH/ALDH2), causing oxidative damage and fibrosis. In NAFLD, mitochondrial dysfunction, ER stress, and lipotoxicity drive ROS overproduction due to metabolic dysregulation. Both diseases share ROS-mediated pathways, including mitochondrial/ER dysfunction, inflammation, and impaired lipid metabolism, accelerating steatosis to cirrhosis and cancer. Antioxidants, ER modulators, and lifestyle changes show therapeutic potential but require further clinical validation. Future research should leverage multi-omics and targeted therapies to optimize ROS-focused interventions for ALD and NAFLD.

Keywords: alcoholic fatty liver disease; nonalcoholic fatty liver disease; reactive oxygen species.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Mechanisms of ROS generation in NAFLD.
Figure 2
Figure 2
Mechanism of ROS generation in ALD.
Figure 3
Figure 3
Common mechanisms of ROS in ALD and NAFLD.
Figure 4
Figure 4
ROS-induced liver damage. Continuous oxidative stress can transform the liver through simple steatohepatitis, steatohepatitis, and even hepatocellular carcinoma.
See this image and copyright information in PMC

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