Oxidative stress and antioxidant therapeutic mechanisms

Pharmacol Ther. 2026 Feb:278:108962. doi: 10.1016/j.pharmthera.2025.108962. Epub 2025 Nov 30.

Abstract

Oxidative stress is now understood as a disturbance in the cellular redox balance, involving the accumulation of reactive oxygen, nitrogen, and other reactive species beyond the capacity of antioxidant defenses, with effects that range from essential redox signaling to harmful oxidative damage. Reactive oxygen and nitrogen species are generated from both endogenous metabolic processes and exogenous environmental factors. While controlled levels of oxidative stress contribute to cellular signaling and homeostasis, excessive oxidative damage can lead to pathological conditions, including cardiovascular diseases, diabetes, neurodegenerative disorders, inflammatory conditions, and cancer. To counteract oxidative damage, the body employs a complex antioxidant defense system, comprising endogenous enzymatic and non-enzymatic mechanisms, as well as exogenous dietary antioxidants. Therefore, understanding the regulatory pathways and mechanisms of antioxidants is essential for exploring their role in disease prevention, aging, and immune function. This review provides a comprehensive analysis of oxidative stress, its impact on cellular function, and its involvement in disease pathogenesis. Furthermore, it discusses current therapeutic intervention mechanisms, including dietary strategies, pharmacological antioxidants, and clinical trials evaluating antioxidant efficacy. Finally, emerging research directions, such as novel antioxidant compounds, gene therapy, and personalized antioxidant treatments, are highlighted as potential avenues for future exploration.

Keywords: Antioxidants; Disease pathogenesis; Oxidative stress; Reactive oxygen species; Therapeutic targets.

Publication types

  • Review

MeSH terms

  • Animals
  • Antioxidants* / pharmacology
  • Antioxidants* / therapeutic use
  • Humans
  • Oxidative Stress* / drug effects
  • Oxidative Stress* / physiology
  • Reactive Oxygen Species / metabolism

Substances

  • Antioxidants
  • Reactive Oxygen Species