Abstract

Metabolic toxicity is an increasingly recognized contributor to the pathogenesis and progression of chronic 
diseases, including diabetes, cardiovascular disorders, neurodegenerative conditions, cancer, and chronic kidney 
disease. It arises from sustained metabolic dysregulation that leads to the accumulation of toxic intermediates, 
impaired energy homeostasis, and cellular dysfunction. Central to this process are oxidative stress and chronic 
low-grade inflammation, which interact in a self-perpetuating cycle to damage biomolecules, disrupt signaling 
pathways, and impair tissue function. Despite extensive research on metabolic abnormalities in chronic disease, the 
integrated roles of oxidative stress and inflammation in driving metabolic toxicity remain underappreciated. This 
review examines the mechanistic links between metabolic dysregulation, reactive oxygen species generation, 
inflammatory signaling, and cellular toxicity. We discuss how oxidative stress and inflammation contribute to 
mitochondrial dysfunction, insulin resistance, endothelial damage, and organ-specific pathology across major 
chronic diseases. Understanding metabolic toxicity as a redox- and inflammation-driven process offers new 
insights into disease mechanisms and highlights potential therapeutic strategies aimed at restoring metabolic and 
redox homeostasis rather than targeting isolated disease endpoints.