Abstract

The liver is a central organ for metabolism and detoxification, continually exposed to both endogenous and 
exogenous toxins. Oxidative stress, caused by an imbalance between free radicals and antioxidant defenses, plays a 
critical role in liver injury. Antioxidants-molecules that neutralize reactive oxygen species (ROS)-are crucial for 
protecting hepatocytes against oxidative damage. However, interactions between antioxidants and toxins can yield 
complex outcomes. While many antioxidants decrease toxin-induced liver injury by modulating signaling pathways 
and enhancing detoxification, under certain conditions, they may also interact with pro-oxidant systems or interfere 
with metabolic processes, potentially causing harm. This review examines the molecular mechanisms by which 
antioxidants mitigate toxin-induced liver damage, the pathways underlying their protective effects, and the 
circumstances in which antioxidant–toxin interactions might pose risks. Key antioxidant systems and signaling 
pathways, such as nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione metabolism, and phase I/II 
detoxification enzymes, are explored. We also highlight clinical evidence and limitations in current research, 
emphasizing the need for context-sensitive understanding of antioxidant use in liver health.