Antioxidant Defense Failure in Diabetic Immunopathy: Mechanistic Insights Into Oxidative Stress–Driven Immune Dysfunction

Bizimana Rukundo T.

Faculty of Biological Sciences Kampala International University Uganda

ABSTRACT

Diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), is increasingly recognized as a state of chronic immunometabolic dysfunction driven in large part by oxidative stress and impaired antioxidant responses. Hyperglycaemia, dyslipidaemia, and adipose tissue inflammation collectively generate excessive reactive oxygen species (ROS), overwhelming endogenous antioxidant systems such as the Nrf2-Keap1 pathway, glutathione (GSH), thioredoxin, catalase, and superoxide dismutase. The resulting oxidative stress alters immune cell signalling, promotes inflammatory cytokine production, disrupts leukocyte recruitment, and impairs both innate and adaptive immune responses. This constellation of abnormalities-termed diabetic immunopathy-contributes to increased susceptibility to infections, impaired wound healing, suboptimal vaccine responses, and persistent low-grade inflammation that drives cardiometabolic complications. This review synthesizes mechanistic evidence on how antioxidant defense failure shapes immune dysregulation in diabetes, emphasizing the molecular pathways through which ROS modify immune receptors, disrupt cytokine signalling, promote post-translational modifications of proteins, and induce epigenetic reprogramming of immune cells. Additionally, it analyses the interplay between mitochondrial dysfunction, endoplasmic reticulum (ER) stress, ferroptosis, and immune cell exhaustion. Finally, emerging therapeutic strategies-including Nrf2 activators, mitochondrial-targeted antioxidants, dietary polyphenols, and metabolic modulators evaluated for their potential to restore redox balance and reverse immunopathy. Integrating immunology, redox biology, and metabolic disease, this article provides a comprehensive framework for understanding oxidative stress–driven immune dysfunction in diabetes and highlights potential precision interventions targeting redox–immune pathways.

Keywords: diabetic immunopathy, oxidative stress, Nrf2, immune dysfunction, antioxidant defense

 

CITE AS: Bizimana Rukundo T. (2026). Antioxidant Defense Failure in Diabetic Immunopathy: Mechanistic Insights Into Oxidative Stress–Driven Immune Dysfunction. IDOSR JOURNAL OF SCIENCE AND TECHNOLOGY 12(1):34-39. https://doi.org/10.59298/IDOSR/JST/26/113.3439