Abstract

In recent years, significant attention has been given to the field of free radicals in chemistry. Reactive oxygen species (ROS) and reactive nitrogen species are produced by various endogenous systems in the body, exposure to different physical and chemical conditions, or pathological states. A balance between free radicals and antioxidants is crucial for proper physiological function. If free radicals overwhelm the body’s ability to regulate them, a condition known as oxidative stress occurs. Consequently, free radicals can adversely alter lipids, proteins, and DNA, leading to the development of several human diseases. As a result, the use of external antioxidant sources may help combat oxidative stress. Recently, artificial antioxidants such as butylated hydroxytoluene and butylated hydroxyanisole have been reported to be harmful to human health. Therefore, the search for effective and non-toxic natural compounds with antioxidant activity has intensified in recent years. This review provides a brief overview of the cellular damage caused by oxidative stress and the role of dietary antioxidants as functional foods in managing human diseases.

Introduction

Recent advancements in the study of free radicals and reactive oxygen species (ROS) in biology have ushered in a medical revolution, promising a new era of health and disease management. Ironically, while oxygen is essential for life, in certain conditions, it can have harmful effects on the human body. Many of the harmful effects of oxygen are due to the formation and activity of various chemical compounds known as ROS. The terms “free radicals” and “antioxidants” have become common in modern discussions about disease mechanisms.

What Are Free Radicals?

A free radical is defined as any molecular species capable of existing independently and containing an unpaired electron in an atomic orbital. The presence of an unpaired electron leads to specific common properties shared by most radicals. Many free radicals are unstable and highly reactive. They can either donate an electron to other molecules or accept an electron, thus acting as oxidants or reducing agents.

The most important oxygen-containing free radicals involved in many disease conditions include hydroxyl radicals, superoxide anion radicals, hydrogen peroxide, singlet oxygen, hypochlorite, nitric oxide radicals, and peroxynitrite radicals. These highly reactive species can damage biological molecules such as DNA, proteins, carbohydrates, and lipids in the nucleus and membranes of cells.

Free Radical Production in the Human Body

Free radicals and other ROS are generated either from essential metabolic processes within the human body or from external sources such as exposure to X-rays, ozone, smoking, air pollutants, and industrial chemicals. The formation of free radicals occurs continuously within cells as a result of enzymatic and non-enzymatic reactions.

Enzymatic reactions that act as sources of free radicals include those involved in the respiratory chain, phagocytosis, prostaglandin synthesis, and the cytochrome P-450 system. Free radicals can also form in non-enzymatic reactions, such as the oxygen reaction with organic compounds or ionizing reactions.

Free Radicals in Biology

It is expected that free radical reactions will lead to progressive, undesirable changes that accumulate throughout the body with age. Such changes are relatively common for everyone as they age. However, genetic factors and environmental influences modify these patterns, which manifest as diseases at specific ages, determined by genetic and environmental factors. Cancer and atherosclerosis (arteriosclerosis) are major causes of death associated with free radicals.

The onset and promotion of cancer are linked with chromosomal defects and oncogene activation. Free radical reactions can lead to tumor formation, especially in response to ionizing radiation. Studies on atherosclerosis suggest that the disease may arise from free radical reactions involving dietary lipids in the arterial wall, generating peroxides and other harmful substances that damage endothelial cells and cause changes in the arterial wall.

Oxidative Stress

The term oxidative stress describes a condition where there is an imbalance between the production of free radicals and the body’s antioxidant defenses. Oxidative stress, caused by this imbalance, is associated with damage to various molecular species, including lipids, proteins, and nucleic acids. Short-term oxidative stress can occur in tissues damaged by trauma, infection, thermal injury, hypertoxicity, toxins, or excessive exercise. Damaged tissues increase the production of radical-generating enzymes (such as xanthine oxidase, lipoxygenase, cyclooxygenase) and activate phagocytes, leading to the release of free iron, copper ions, or disruption in electron transport chains, causing additional ROS production. Oxidative stress is associated with the initiation, promotion, and progression of cancer, as well as the side effects of radiation and chemotherapy. ROS also plays a role in inducing and exacerbating conditions like diabetes, age-related eye diseases, and neurodegenerative diseases such as Parkinson’s disease.

Oxidative Stress and Human Diseases

Oxidative stress is believed to play a significant role in various conditions, including atherosclerosis, inflammatory conditions, some cancers, and aging processes. It is now known that oxidative stress contributes to many inflammatory diseases (such as arthritis, vasculitis, glomerulonephritis, lupus erythematosus, adult respiratory diseases), ischemic diseases (such as heart disease, stroke, ischemic bowel disease), hemochromatosis, acquired immune deficiency syndrome (AIDS), emphysema, organ transplantation, gastric ulcers, hypertension, preeclampsia, neurodegenerative disorders (such as Alzheimer’s disease, Parkinson’s disease, muscular dystrophy), alcohol addiction, smoking-related diseases, and many others.

Excessive oxidative stress can lead to the oxidation of lipids and proteins, altering their structure and function. Many studies provide clear evidence that DNA and RNA are also susceptible to oxidative damage, with DNA being a primary target in aging and cancer.

Antioxidants: The Body’s Defense Mechanism

An antioxidant is a molecule stable enough to donate an electron to a free radical, neutralizing it and reducing its capacity to cause damage. Antioxidants primarily delay or inhibit cellular damage by scavenging free radicals. These low molecular-weight antioxidants safely interact with free radicals and terminate the chain reaction before vital molecules are damaged.

Some antioxidants, including glutathione, ubiquinol, and uric acid, are produced naturally within the body during metabolism. Other lighter antioxidants are found in the diet. While several enzymatic systems in the body eliminate free radicals, key micronutrient antioxidants include vitamin E, vitamin C (ascorbic acid), and β-carotene. Since the body cannot produce these micronutrients, they must be obtained through diet. Additionally, consuming more functional foods rich in antioxidants, such as alkaline ionized waters, is becoming an increasingly important strategy. Alkaline ionized waters are considered superfoods with antioxidant properties that protect DNA from oxidative damage, suppress lipid peroxidation, and even have anti-cancer effects.

Conclusion

The ongoing research into free radicals and antioxidants underscores their significant roles in human health and disease. Balancing oxidative stress through dietary antioxidants, especially from natural sources, is crucial for mitigating the risk of various diseases, including cancer, cardiovascular diseases, and neurodegenerative disorders. By understanding and managing oxidative stress, we can better promote overall health and longevity.