Antioxidants and Reactive Oxygen Species: Shaping Human Health and Disease Outcomes

Abstract

Reactive molecules, including oxygen and nitrogen species, serve dual roles in human physiology. While they function as essential signaling molecules under normal physiological conditions, they contribute to cellular dysfunction and damage when produced in excess by normal metabolism or in response to stressors. Oxidative/nitrosative stress is a pathological state, resulting from the overproduction of reactive species exceeding the antioxidant capacity of the body, which is implicated in several chronic human diseases. Antioxidant therapies aimed at restoring redox balance and preventing oxidative/nitrosative stress have demonstrated efficacy in preclinical models. However, their clinical applications have met with inconsistent success owing to efficacy, safety, and bioavailability concerns. This summative review analyzes the role of reactive species in human pathophysiology, the mechanisms of action of antioxidant protection, and the challenges that hinder their translation into effective clinical therapies in order to evaluate potential emerging strategies such as targeted delivery systems, precision medicine, and synergistic therapeutic approaches, among others, to overcome current limitations. By integrating recent advances, this review highlights the value of targeting reactive species in the prevention and management of chronic diseases.

Keywords: chronic diseases; inflammation; nanomedicine; nitrosative stress; oxidation; oxidative stress; precision medicine.

Figure 1

Schematic illustration depicts the various endogenous and exogenous sources contributing to the generation of reactive oxygen species (ROS) within a cell. Key endogenous sources include oxidative phosphorylation in mitochondria; enzymatic reactions involving xanthine oxidase, cytochrome P450, nitric oxide synthases, and cyclooxygenases; and NADPH oxidase activity, metabolic reactions in peroxisomes, and endoplasmic reticulum (ER) stress with unfolded protein response (UPR). Exogenous contributors include radiation, lifestyle and dietary factors, environmental pollutants, and the cellular uptake of microbes, nanoparticles, and xenobiotics. These processes lead to the formation of ROS such as superoxide (O₂⁻), hydrogen peroxide (H₂O₂), and hydroxyl radicals (OH⁻), which can affect cellular homeostasis and contribute to oxidative stress. Modified from [16].

Figure 2

Canonical schematic outlines the sources and biochemical pathways of reactive oxygen species (ROS) and reactive nitrogen species (RNS). (A) Endogenous RNS are generated via nitric oxide synthase (NOS), producing nitric oxide (NO⁻) and peroxynitrite (ONOO⁻) through interaction with myeloperoxidase. (B) Exogenous sources, such as environmental pollutants, diet, tobacco smoke, pathogens, and UV radiation, also contribute to RNS production. (C) The diagram details the interplay between ROS and RNS, highlighting the enzymatic generation of superoxide (O₂⁻), hydrogen peroxide (H₂O₂), hydroxyl radicals (OH⁻), and downstream nitrogen species from L-arginine through NO synthesis and emphasizing their interconnected redox biology. Modified from [36].

Figure 3

Schematic shows the dual role of reactive oxygen and nitrogen species (RONS) in cellular physiology. At basal levels, RONS support homeostasis, enabling normal growth and metabolism. However, both insufficient and excessive RONS levels lead to impaired physiological function. Low RONS can reduce proliferation and weaken host defenses, while high RONS cause random cellular damage or activate signaling pathways, contributing to aging, disease, and cell death. Modified from [48].