REDOX MEDICINE THE DOUBLE-EDGED SWORD OF OXIDANTS
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ou may have read the packaging on an item at the grocery store and seen the words “High in Antioxidants” shining out. Antioxidants must be important then – why else advertise it? If antioxidants are good, then oxidants must be the opposite. So, what’s the deal with oxidation? The biology of oxidants is a topic of interest in many subspecialities of science – ranging from free radical chemistry to cancer biology. In order to understand these molecules, it is important to establish some terminology:
Oxidation: Loss of electron Reduction: Gain of electron Oxidizing agent or oxidant: Gains the electron, is reduced Reducing agent or antioxidant: Loses the electron, is oxidized Now that we’ve clarified some terms, we can look at oxidants on a physiological level. Oxidants are formed from biological process including during normal metabolism. In the mitochondria, oxidative phosphorylation is the transfer of electrons in a baton-relay race that ends with the final electron acceptor, (the final oxidant), H2O. Normal chemical kinetics sometimes result in H2O being further reduced into reactive oxygen species (ROS) such as superoxide (O2-) or hydrogen peroxide (H2O2), the former of which is also a free radical. ROS can continue to propagate and become free radicals that interact with and modify lipids, proteins and most dangerously, DNA. While there are homeostatic counter molecules, antioxidants, there are instances where the levels of oxidants greatly exceed those of antioxidants and results in a state of biological oxidative stress. The effect of oxidative stress is oxidative damage to the essential macromolecules. 26 IMMpress Vol. 11 No. 2 2023
Oxidative damage can have beneficial uses and detrimental effects. During immune responses against virus-infected cells or bacteria, phagocytes cells engulf pathogens into a phagocytic vacuole where they are met with a oxidative burst, an onslaught of peroxides, superoxides and other oxidants meant to destroy the pathogen. In this scenario, cells have harnessed the destructive power of oxidants in a controlled and contained manner as an immune line of defense. In contrast, the unchecked accumulation of oxidant species can lead to devastating damage. This can occur in a number of ways:
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External sources of oxidants: The most notable exogenous source of oxidants is cigarette smoke, which introduces considerable oxidative stress and damage to DNA. Dysregulation of homeostatic checks: When enzymes that control oxidant levels develop mutations, the delicate oxidant and antioxidant balance can be skewed towards a pro-oxidant state. Antioxidant deficiency: Without the counter-defense of antioxidant molecules and the enzymes that generate them, ROS propagation can go forward unchecked.
A pro-oxidant state has trickle-down effects that are implicated in a multitude of illnesses including cardiovascular, neurological, respiratory, and ocular diseases as well as multi-organ cancers. A simple example of disease development is in atherosclerosis where oxidation of lipids in a process called lipid peroxidation contributes to plaque formation. Thus emerges the field of redox medicine, which aims to harness and reinforce the antioxidant defense system.
