Pathophysiology of CLD: Oxidative Stress and Antioxidant Mechanisms that may Limit its Progression.

[INTRODUCTION] Chronic liver disease (CLD) represents a progressive condition culminating in fibrosis and, ultimately, cirrhosis or hepatocellular carcinoma. A growing body of evidence implicates oxidative and nitrosative stress as key mediators in the pathogenesis of CLD.

[OBJECTIVE] This review aims to summarize the role of oxidative stress in CLD progression and to highlight therapeutic strategies targeting redox imbalance and related signaling pathways.

[METHODS] Relevant literature from preclinical and clinical studies was reviewed, with emphasis on mechanisms of oxidative and nitrosative stress, signaling pathways involved in fibrogenesis, and emerging therapeutic interventions targeting redox imbalance and the gut-liver axis.

[RESULTS AND DISCUSSION] Reactive oxygen and nitrogen species contribute to hepatocyte damage, hepatic stellate cell activation, and extracellular matrix accumulation. Mitochondrial dysfunction, endoplasmic reticulum stress, and disrupted redox homeostasis induce tissue injury and fibrogenesis. Various signaling pathways, including Nrf2/Keap1, AMPK/SIRT1, JNK, PI3K/Akt/mTOR, and TGF-β/SMAD, serve as critical links between oxidative imbalance and fibrotic progression. The antifibrotic potential of antioxidants such as vitamin E, lipoic acid, berberine, and polyphenolic compounds is increasingly validated in preclinical and clinical studies. Additionally, modulation of NOX enzymes and support of endogenous defenses offer promising therapeutic avenues. The gut-liver axis and microbial dysbiosis further exacerbate redox disturbance, underscoring the systemic nature of liver injury. Probiotic and prebiotic therapies have shown hepatoprotective effects in NAFLD models.

[CONCLUSION] In conclusion, targeting oxidative stress and its associated pathways represents a compelling strategy to attenuate or even reverse liver fibrosis, presenting a promising therapeutic strategy that could be integrated into clinical practice.