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Context-Dependent Toxicity of Antioxidants: When Protective Molecules Become Harmful

Author: Mpora Kakwanzi Evelyn
Publisher: NEWPORT INTERNATIONAL JOURNAL OF BIOLOGICAL AND APPLIED SCIENCES (NIJBAS)
Published: 2026
Section: School of Pharmacy

Abstract

Antioxidants are traditionally viewed as beneficial agents that defend cells against oxidative damage by 
neutralizing reactive oxygen species (ROS) and reactive nitrogen species (RNS). However, accumulating evidence 
demonstrates that their impact is highly context-dependent: under specific biochemical conditions, physiological 
states, and dosages, antioxidants can shift from protective to harmful roles. This review synthesizes current 
research showing that antioxidants may act as pro-oxidants, disrupt redox signaling, contribute to disease 
progression, and interfere with therapeutic outcomes. We explore the molecular mechanisms underlying this 
duality, including redox potential, concentration-dependent effects, presence of transition metals, and interactions 
with endogenous antioxidant networks. Clinical and toxicological implications are discussed, with examples from 
cancer biology, pharmacology, and environmental exposure scenarios. Understanding the nuanced behavior of 
antioxidants is critical for optimizing their application in diet, supplementation, and therapeutic settings, and for 
avoiding unintended adverse effects.