The Role of Free Radicals and Oxidative Stress in Chronic Diseases: A Comprehensive Review of Mechanisms and Therapeutic Interventions

Abstract

Oxidative stress, resulting from an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, plays a fundamental role in the onset and progression of numerous chronic diseases, including neurodegenerative, cardiovascular, metabolic, and oncological conditions. Although extensive research has elucidated the molecular mechanisms underlying redox homeostasis, therapeutic translation remains elusive. This comprehensive review examines current knowledge on the sources and biochemistry of free radicals, the cellular consequences of oxidative stress, endogenous and dietary antioxidant defense systems, and the clinical and nutritional interventions developed to modulate redox balance. It also examines emerging therapeutic strategies and research gaps within the field. Free radicals inflict significant damage on lipids, proteins, and nucleic acids, contributing to mitochondrial dysfunction and systemic inflammation. Endogenous defense systems such as superoxide dismutase, catalase, and glutathione peroxidase provide partial protection, while exogenous antioxidants, derived from diet or supplements, offer additional but context-dependent benefits. Clinical interventions show inconsistent outcomes due to variable bioavailability, dosing challenges, and inter-individual variability. Advances in omics-based technologies, AI-driven modeling, and redox-sensitive biomarkers present new avenues for targeted therapies. By elucidating the mechanistic underpinnings and therapeutic implications of oxidative stress, the present work aims to inform future research and contribute to the development of targeted antioxidant therapies to combat the chronic disease burden.

Keywords: Oxidative Stress; Free Radicals; Chronic Diseases; Antioxidant Defense Systems; Redox Biology; Therapeutic Interventions; Reactive Oxygen Species (ROS); Mechanisms of Damage; Clinical Trials; Disease Prevention.

DOI: 10.7176/JHMN/119-08

Publication date: August 30th 2025