Oxidative stress and antioxidants: biochemical mechanisms, medical applications, and bioavailability of natural compounds

Abstract

Antioxidants form a vital defense system to protect cells from damage caused by reactive oxygen and nitrogen species (ROS/RNS). Oxidative stress arises from the imbalance between the rate of free radical production and the inhibitory capacity of the cellular defense system, leading to lipid peroxidation, protein damage, and DNA mutations, which pave the way for cardiovascular diseases, neurodegeneration, and cancer. The defense mechanism is integrated through two main branches: the enzymatic self-defense, which includes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) to dismantle oxidative components. Non-enzymatic external: It includes vitamins (C, E) and phenolic compounds that neutralize radicals through electron transfer (SET) or hydrogen atoms (HAT) and metal chelation. Cells regulate their oxidative response through the Nrf2-ARE signaling pathway, which stimulates the transcription of phase II detoxifying enzymes upon exposure to stress. Despite the medical benefits of natural compounds, the use of synthetic supplements in excessive doses may lead to adverse effects known as the "Antioxidant Paradox," where they turn into pro-oxidant agents. Recent research shows that the low bioavailability of natural compounds is the biggest obstacle to their therapeutic efficacy, making nano-encapsulation techniques a promising solution to protect them and increase their cellular absorption. It is recommended to rely on a balanced diet and develop nanocarriers instead of unregulated high doses.