INTRODUCTION:

Because of their two functions in human health, free radicals which are molecules or atoms with unpaired electrons, have gained attention in biomedical research. These reactive species, which include oxygen-derived radicals such as superoxide anion (O₂−) and hydroxyl radical (OH⋅), as well as non-radical oxidants like hydrogen peroxide (H2O2), are produced naturally within the human body during normal cellular metabolism. However, outside factors like pollution, UV light, and smoking also contribute to the generation of free radicals, which are molecules or atoms with unpaired electrons¹. Low quantities of free radicals are necessary for physiological functions like immunological responses and cell signaling, but when their synthesis and elimination are out of balance, oxidative stress results, a state linked to the etiology of many chronic illnesses². Free radicals' strong reactivity, which allows them to interact with biomolecules and cause structural and functional damage, controls their chemistry. The characteristic consequences of unregulated free radical activity include DNA damage, lipid peroxidation, and protein oxidation, which all contribute to cellular malfunction and the advancement of illness². Notwithstanding these negative consequences, the human body has an advanced antioxidant defense system that includes non-enzymatic antioxidants like glutathione and vitamins C and E as well as enzymatic antioxidants like catalase and superoxide dismutase (SOD)³. Together, these systems neutralize free radicals and preserve redox equilibrium.

The various functions of free radicals in human health are examined in this review, beginning with their origins, chemical makeup, biological impacts, and the processes via which they cause oxidative stress. It also emphasizes possible therapeutic approaches and talks about the vital function endogenous and exogenous antioxidants play in reducing oxidative damage. This review seeks to shed light on the complex relationship between antioxidants and free radicals in order to manage oxidative stress and the health consequences that go along with it.

Sources of Free Radicals:

Numerous processes that take place both inside the human body (endogenous sources) and outside the body as a result of lifestyle or environmental influences (exogenous sources) produce free radicals. It is essential to comprehend these sources in order to control their negative health impacts⁴.

Endogenous Sources of Free Radicals:

Naturally occurring endogenous free radicals are created during regular physiological functions. These consist of immunological responses, metabolic reactions, and enzymatic processes involving reactive intermediates.

Mitochondrial Electron Transport Chain (ETC):

The main location where free radicals are produced during aerobic respiration is the mitochondria. The ETC reduces oxygen to water by transferring electrons through complexes. But a tiny portion of oxygen molecules undergo partial reduction, creating superoxide anion (O₂⋅−):

O₂+e−→O₂⋅−

Hydrogen peroxide (H2O2) and hydroxyl radicals are two further reactive oxygen species (ROS) that can be created by additional reactions with superoxide anion (OH⋅):

O₂⋅−+O₂⋅−+2H+→H₂O₂+O₂

H₂O₂+Fe2+→OH⋅+OH−+Fe3+ (Fenton Reaction)

Immune System Activation

To eliminate infections, phagocytic cells like neutrophils and macrophages release free radicals during immune reactions. The creation of superoxide anion from oxygen is catalyzed by the enzyme NADPH oxidase:

When interacting with nitric oxide (NO⋅), this superoxide anion can produce additional reactive species, including peroxynitrite (ONOO−):

O2⋅−+NO⋅→ONOO−

Enzymatic Reactions

Free radicals are a byproduct of several enzymatic processes:

Hypoxanthine is converted to xanthine-by-xanthine oxidase, which also produces hydrogen peroxide and superoxide anion.

When incomplete electron transfer occurs, cytochrome P450 enzymes, which metabolize xenobiotics, can produce reactive intermediates, such as ROS.

Peroxisomal Activity

Hydrogen peroxide is a byproduct of the beta-oxidation process that peroxisomes use to break down fatty acids. Despite detoxifying H2O2, some may evade catalase and cause oxidative damage.

Transition Metals

When transition metals like iron (Fe) and copper (Cu) go through redox cycling, free radicals are produced. For example:

Fe2+ + H2O2 → Fe3+ + OH⋅ + OH−

Exogenous Sources of Free Radicals:

Exogenous sources are outside variables that either cause or encourage the body to produce free radicals. These include of radiation, lifestyle decisions, and environmental contaminants.

Environmental Pollutants:

Free radicals and reactive species are found in pollutants like cigarette smoke, industrial emissions, and vehicle exhaust. Thousands of free radical species, such as NO⋅, CO2⋅−, and OH⋅, are found in cigarette smoke alone.

Ultraviolet (UV) and Ionizing Radiation:

UV causes mutations by generating reactive oxygen species (ROS) such as superoxide anion, hydrogen peroxide and the hydroxyl radical⁵. Nucleotides are highly susceptible to free radical injury. Oxidation of nucleotide bases promotes mispairing outside of normal Watson-Crick parameters, causing mutagenesis⁶. By stimulating electrons and rupturing chemical bonds, UV light from the sun can lead to the production of free radicals in skin cells. When ionizing radiation (such as X-rays and gamma rays) interacts with bodily water, hydroxyl radicals are created:

Xenobiotics and Drugs:

There is a large amount of clear evidence linking the excessive production of ROS with the consumption of different drugs. These drugs include anticancer therapies, nonsteroidal anti-inflammatory drugs (NSAIDs), antiretroviral agents, antipsychotics, and pain relievers⁷. Through metabolic activation, several medications (such as chemotherapeutics) and environmental pollutants can cause the creation of free radicals. For instance, when paracetamol (acetaminophen) is consumed, hazardous intermediates are produced during metabolism, which leads to the creation of free radicals.

Smoking and Alcohol Consumption:

Smoking lowers endogenous antioxidant availability, resulting in oxidative stress. This can activate NF-κB, which can then trigger the expression of proinflammatory mediators. Produces a lot of RNS and ROS, such as nitric oxide and superoxide. Both acute and chronic alcohol use raise ROS, which is partly caused by the acetaldehyde that is produced as a byproduct of ethanol metabolism. Acetaldehyde can lead to ER stress by changing calcium homeostasis and increasing the generation of ROS ^8,9,10.

Dietary Factors:

Constant availability of oxidizable substrates at rest, such as glucose and D-galactose, reduces oxidative phosphorylation, raising the possibility that a greater proportion of electrons will leak from the ETC and produce ROS 11. Processed food contaminants, particularly nitrites, can produce reactive nitrogen species (RNS), which fuel the production of free radicals and oxidative stress. The production of reactive nitrogen species and free radicals is greatly aided by contaminants found in processed foods, especially nitrites and other additives. These negative effects can be lessened by consuming less highly processed foods and more fresh, minimally processed foods that are high in antioxidants. A list of typical food additives and pollutants that may aid in this process is shown below:

Artificial Nitrites and Nitrates

Advanced oxidative processes (AOPs) in water treatment generate reactive nitrogen species (RNS) along with ROS and RCS due to the presence of nitrates, nitrites, and natural organic matter. RNS can form through photodecomposition or reactions with strong radicals. In food, nitrates and nitrites used as preservatives in meats like bacon and sausages can turn into harmful nitrosamines under heat or acidic conditions. Nitrosamines produce free radicals that damage DNA and are linked to cancer. Common nitrate-based additives include sodium nitrate and potassium nitrate, used widely in processed and cured foods^11,12.

How Nitrites are Labeled on Food Products:

Nitrites may be referred to by the following names on food labels: Potassium nitrite and potassium nitrate are E249 and E252. Sodium nitrite and sodium nitrate are E250 and E251, respectively.

Natural Sources of Nitrites in Foods (Processed with Nitrate Additives):

Certain foods include nitrates, such as potassium and sodium nitrates, which are transformed into nitrites during processing. Examples include "Nitrate-cured" processed meats sold as "natural" substitutes and leafy green vegetables (like celery) used in "natural" curing methods.

Mechanism of free radical formation by nitrites and nitrates:

Nitrites (NO2−) can form nitric oxide (NO⋅) and other RNS under acidic conditions (e.g., in the stomach):

NO2−→NO⋅+O2⋅−→ONOO−

Peroxynitrite (ONOO−) is a potent RNS that can damage lipids, proteins, and DNA.

The body may produce free radicals as a result of a number of artificial food additives, such as artificial colorants, artificial sweeteners, preservatives, flavorings, and emulsifiers. These free radicals raise the likelihood of developing chronic illnesses like cancer, neurological disorders, and cardiovascular disorders by causing oxidative stress and damage. Even while many of these additives are considered acceptable to eat in moderation, consuming too much of them, especially in processed or artificially flavored foods, may have negative oxidative consequences on the body.

Polycyclic Aromatic Hydrocarbons (PAHs):

Benzo[a]pyrene, phenanthrene, and fluoranthene are examples of PAHs, which are toxic substances that are usually created by incomplete combustion. They are frequently found in sources such as industrial pollutants, grilled and smoked meals, automobile emissions, and tobacco smoke. Despite not being purposefully added to food, PAH contamination, particularly during high-temperature cooking or smoking, poses serious health risks because of its mutagenic and carcinogenic qualities. They are created when food is cooked at high temperatures, including when grilling, smoking, or barbecuing. Fish, fowl, and charred meats are among the sources, as are smoked and cured meats. Anthracene, Pyrene, Chrysene, Benzo[b]fluoranthene, Dibenzo[a,h]anthracene, Benzo[k]fluoranthene, and Indeno[1,2,3-cd] pyrene are other examples of PAHs¹⁶.

Heterocyclic Amines (HCAs):

Heterocyclic amines (HCAs) are carcinogenic and mutagenic compounds commonly formed when meat is cooked at high temperatures like grilling or frying. They result from reactions between creatine and amino acids in muscle tissue. PhIP is the most prevalent HCA found in cooked meats, followed by MeIQx. Studies link chronic exposure to HCAs with increased cancer risk in humans and animals. Common HCAs in cooked meats include PhIP, MeIQx, MeAIP, DiMeIQx, and IQ.

Advanced Glycation End Products (AGEs):

Advanced Glycation End Products (AGEs) are harmful compounds formed when sugars react non-enzymatically with proteins, lipids, or nucleic acids. Their formation is accelerated by factors like high blood sugar, poor diet, and smoking. AGEs are linked to complications in diabetes, including atherosclerosis, retinopathy, and kidney failure, due to their accumulation in the extracellular matrix. They also contribute to aging and chronic diseases such as heart disease and Alzheimer’s. Key AGEs include CML, MG-H1, Pyrraline, and cross-linked AGEs^18,19.

Acrylamide:

Acrylamide is a chemical classified by the International Agency for Research on Cancer (IARC) as a probable human carcinogen and known neurotoxin. It forms mainly through the Maillard reaction when foods with reducing sugars and asparagine are cooked at high temperatures. Common sources include baked goods, fried potato products, coffee, roasted nuts, and breakfast cereals. Long-term consumption of acrylamide-rich foods raises health concerns. Its presence is especially high in starchy foods subjected to baking, roasting, or frying²².

Artificial Food Additives and Generation of Free Radicals:

Certain artificial food additives may cause the body to experience oxidative stress or produce free radicals. Reactive oxygen species (ROS) are very reactive molecules that have the potential to harm cells and tissues. These additives can interact with different chemicals in food or the digestive system to promote the generation of ROS. Free radicals, which can harm tissues and play a role in inflammation and chronic illnesses, can be released when these dyes are broken down or metabolized in the body. The following artificial food additives have been demonstrated to cause oxidative stress or produce free radicals: Artificial Colors (Synthetic Dyes), Artificial Sweeteners, Preservatives, Artificial Flavorings, Artificial Emulsifiers, and Heavy Metals in Food Processing.

Trans Fats and Oxidized Fats:

Unhealthy fats like oxidized and trans fats can have a big effect on people's health by raising their risk of inflammation, heart disease, and other long-term conditions. Both kinds of fats can be found in a variety of cooked and processed foods, and encouraging healthy diets requires knowledge of their sources, impacts on health, and origins ^{24, 25}. Trans fats are unsaturated fats formed through hydrogenation and occur both naturally and artificially. Artificial trans fats are found in margarine, shortening, baked goods, fried fast foods, packaged snacks, and frozen meals. Natural trans fats exist in small amounts in beef, lamb, and dairy products. Oxidized fats form when fats react with oxygen, producing harmful compounds like peroxides and free radicals. They are commonly found in fried foods, reused cooking oils, and processed snacks like chips, crackers, and cookies. Consuming oxidized fats has been linked to inflammation, cell damage, and increased risk of chronic diseases.

Pesticide Residues:

Pesticides like pyrethroids, carbamates, and organophosphates are used to protect crops but can leave harmful residues in food. These chemicals can induce oxidative stress by promoting free radical formation, which may lead to health issues like neurological damage. Washing produce, choosing organic foods, and following pesticide regulations can help reduce health risks²⁶.

3.0 Types of Free Radicals

Free radicals, highly reactive compounds with unpaired electrons, are generated by various cellular and environmental processes ²⁷. They are classified into two main categories: reactive oxygen species (ROS) and reactive nitrogen species (RNS). Excessive levels of these species can lead to oxidative stress, causing cellular damage and contributing to diseases, as summarized in Table 1.

Table 1: Summary of ROS and RNS

Type	Example	Key Formation Process	Reactivity	Biological Role
Reactive Oxygen Species (ROS)	Superoxide anion (O₂⁻)	Mitochondrial respiration, NADPH oxidase	Reacts with other molecules to form H₂O₂, hydroxyl radicals	Cell signaling, immune response, inflammation
	Hydroxyl radical (OH•)	Fenton reaction (Fe²⁺ + H₂O₂)	Highly reactive; damages proteins, lipids, DNA	Involved in immune defense, but causes oxidative damage in excess
	Hydrogen peroxide (H₂O₂)	Generated by superoxide dismutase or cellular metabolism	Can decompose into hydroxyl radicals	Signaling molecule; toxic at high concentrations
Reactive Nitrogen Species (RNS)	Nitric oxide (NO)	Nitric oxide synthase (NOS)	Reacts with superoxide to form peroxynitrite	Blood flow regulation, neurotransmission, immune defense

Interactions of Free Radicals with Biomolecules:

Free radicals are highly reactive and can damage biomolecules like proteins, lipids, and DNA. Excessive free radical production is linked to diseases such as cancer, neurological disorders, and cardiovascular issues. Their damaging effects are due to their ability to steal electrons, triggering further cellular harm²⁸.

Biological Effects of Free Radicals:

Free radicals, especially reactive oxygen species (ROS) and reactive nitrogen species (RNS), are frequently thought of as the only dangerous substances that cause aging and cellular damage. They also have vital physiological roles in a number of biological processes, though. Free radicals contribute to immune system reactions, cellular signaling, and other essential processes that preserve homeostasis when present in moderation^29,30.

Antioxidant Approaches for Minimizing Free Radicals:

The body has developed mechanisms to counteract the harmful effects of free radicals using both endogenous and exogenous antioxidants. Antioxidants neutralize free radicals, maintaining redox balance and preventing oxidative stress-related damage. Endogenous antioxidants, produced within the body, are vital for protecting cells and tissues. These antioxidants are categorized into enzymatic and non-enzymatic types. This section delves into these two main categories of endogenous antioxidants, which play roles in disease prevention and aging mitigation ^{31, 39}.

Vitamins as Dietary Antioxidants:

Vitamins are organic substances that are necessary for several bodily biochemical functions, such as antioxidant protection. By scavenging free radicals and halting oxidative damage to cellular structures, several vitamins function as strong antioxidants ^31,32,46. Such vitamins include Vitamin C (Ascorbic Acid), Vitamin E (Tocopherols and Tocotrienols), and Vitamin A (Beta-Carotene and Retinol).

Polyphenols as Dietary Antioxidants:

Polyphenols are a group of plant chemicals known for their powerful antioxidant properties, which help prevent degenerative diseases such as cancer, heart disease, and neurological disorders. These compounds have additional health benefits, including anti-allergic, antihypertensive, anti-inflammatory, and antimicrobial effects. They are integral to plant-based diets and contribute to improving vascular health and reducing inflammation. Flavonoids and carotenoids are notable examples of polyphenols. Sources of flavonoids include citrus fruits, berries, apples, and onions, while carotenoids are found in colorful vegetables like carrots, spinach, and tomatoes ^33,34,35.

Minerals as Dietary Antioxidants:

Minerals are vital minerals that can directly neutralize free radicals and serve as cofactors for enzymatic antioxidant systems. Zinc and selenium are two minerals that are very crucial for sustaining antioxidant defense mechanisms ³⁶.

Synthetic Antioxidants as Therapeutic Agents:

In addition to naturally occurring antioxidants, synthetic antioxidants are widely used in dietary supplements and medicinal products to combat oxidative stress. These compounds help neutralize free radicals, protecting cells from oxidative damage. While natural antioxidants are crucial for overall health, synthetic antioxidants offer specific therapeutic benefits in preventing and treating diseases related to oxidative stress, such as cancer, heart disease, and neurological conditions. Examples of synthetic antioxidants include butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT), commonly used in food preservation. These synthetic antioxidants are also utilized in clinical settings to enhance antioxidant defenses and support therapeutic treatments ³⁷.

Considerations and Risks of Synthetic Antioxidants:

Although synthetic antioxidants offer health benefits, excessive use can disrupt the body’s natural antioxidant systems, potentially hindering the production of endogenous antioxidants like glutathione. High doses of synthetic antioxidants, such as BHT and BHA, may also be toxic and linked to carcinogenic effects. It’s essential to follow recommended dosages and consult healthcare professionals, as whole food sources of antioxidants provide additional nutritional benefits not found in isolated supplements.

Lifestyle Interventions in Controlling Free Radicals:

Controlling free radicals and reducing their harmful effects on the body are important goals of lifestyle treatments. Highly reactive chemicals known as free radicals can cause oxidative stress if they are not controlled, which can lead to aging, cellular damage, and the onset of many chronic diseases. People can lessen the generation of free radicals and improve the body's capacity to combat them through antioxidant defense mechanisms by changing their lifestyles. The best tactics include eating a healthy, balanced diet, exercising frequently, and avoiding oxidative stressors like pollution and smoking³⁷.

Avoidance of Oxidative Stressors:

Numerous outside variables, also known as oxidative stressors, can raise the production of free radicals and aid in the emergence of chronic illnesses. People can considerably lessen the oxidative load on their bodies by limiting their exposure to these stressors.

A. Smoking:

One of the main causes of oxidative stress and the production of free radicals is smoking. Many harmful substances included in cigarette smoke, including carbon monoxide, tar, and nicotine, cause direct harm to tissues and cells.

Effect of Smoking on Free Radicals: Smoking causes more reactive oxygen species (ROS), such as hydroxyl radicals and superoxide anion, which can harm DNA, proteins, and lipids. Chronic obstructive pulmonary disease (COPD), cardiovascular disorders, and lung cancer are among the illnesses that are accelerated in their development by this oxidative damage. Giving Up Smoking: Giving up smoking improves the body's antioxidant defense systems and lowers the production of free radicals. Quitting smoking lowers the long-term risk of disease by improving cardiovascular health and promoting lung tissue regeneration.

B. Air Pollution:

Air pollution is a major source of free radicals, with pollutants like particulate matter (PM), ozone, NOx, and VOCs generating reactive oxygen species (ROS) that damage respiratory tissues and trigger systemic oxidative stress. PM disrupts mitochondrial function and calcium balance, increasing harmful ROS such as H₂O₂ and •OH. This oxidative damage contributes to diseases like asthma, bronchitis, cancer, and cardiovascular disorders. Limiting pollution exposure, using air purifiers, and staying indoors during high pollution periods can help reduce risk. Antioxidant-rich diets and supplements offer additional protection against pollution-induced oxidative stress. Proactive lifestyle choices are essential in mitigating environmental free radical damage.

Excessive Alcohol Consumption:

Prolonged alcohol consumption produces acetaldehyde and ROS, leading to liver damage, weakened immunity, and increased risk of cancer and heart disease. Alcohol metabolism via ADH and cytochrome P450 generates free radicals that trigger inflammation and oxidative stress. Reducing alcohol intake helps minimize these effects and supports antioxidant defenses. Lifestyle changes like a balanced diet, regular exercise, and avoiding oxidative stressors strengthen the body's ability to combat free radical damage. These habits promote longevity, reduce disease risk, and improve overall health.

Challenges and Future Directions:

Even though our knowledge of free radicals and their function in health and illness has advanced significantly, research on free radicals and antioxidant treatments still faces many obstacles. The limitations of existing antioxidant techniques, new developments in the study of free radicals, and potential avenues for the creation of innovative antioxidant therapeutics are covered in this section.

Limitations in Antioxidant Therapies:

While antioxidant therapies show potential in reducing oxidative damage, several limitations affect their clinical effectiveness. Many antioxidants lack specificity and may neutralize beneficial free radicals, disrupting important processes like immune defense and cell signaling. Poor bioavailability also limits their therapeutic value, as compounds like polyphenols and vitamins C and E are often poorly absorbed. Long-term use of synthetic antioxidants, such as beta-carotene and vitamin E, may pose safety risks, including increased cancer risk in certain groups. Drug interactions further complicate their use. Additionally, incomplete understanding of redox signaling makes it difficult to design antioxidants that target harmful oxidants without affecting necessary physiological functions ^38.,39.

Emerging Trends in Free Radical Research:

Recent advancements in free radical research have revealed their vital roles in aging, disease, and health, highlighting redox signaling as a key player in conditions like cancer, diabetes, and neurodegenerative diseases. Mitochondria are now recognized as both sources and victims of oxidative damage, contributing to aging through mitochondrial dysfunction. Emerging studies show that oxidative stress can alter epigenetic mechanisms, influencing gene expression and disease progression. Understanding these changes opens doors for gene-targeted therapies. Additionally, free radicals are essential in immune responses, aiding in inflammation and pathogen defense. Future therapies must balance their damaging and regulatory roles. This evolving understanding offers novel therapeutic possibilities ^40,41,42.

Development of Novel Antioxidant Strategies:

As understanding of free radicals deepens, novel antioxidant strategies are being developed to provide safer, more effective therapies. Targeted antioxidants like mitoQ aim to neutralize ROS within specific cellular sites such as mitochondria, while phytochemicals like resveratrol and curcumin offer potent natural antioxidant effects. Artificial enzyme mimics replicate the activity of natural enzymes like catalase and SOD, and nanotechnology enables precise delivery of antioxidants to damaged tissues. Gene therapy is also being explored to boost the body’s production of antioxidant enzymes. These innovations address limitations of current therapies and show promise in treating oxidative stress-related diseases^43,44,45.

CONCLUSION:

Free radicals play dual roles in human health—supporting immune function and signaling, but causing oxidative stress when unregulated, leading to aging and diseases like cancer and heart conditions. Antioxidants, both natural and synthetic, are crucial in maintaining redox balance by neutralizing excess free radicals. While dietary antioxidants from fruits and vegetables offer vital protection, current antioxidant therapies face challenges like poor absorption and non-specific action. Understanding redox biology and improving antioxidant strategies are essential to managing oxidative stress. Innovations like targeted delivery, mitochondrial therapies, and gene-based treatments show promise. Continued research is vital for developing effective interventions and improving overall health outcomes.

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Received on 17.01.2025 Revised on 09.07.2025

Accepted on 08.11.2025 Published on 14.02.2026

Available online from February 18, 2026

Research J. Science and Tech. 2026; 18(1):8-16.

DOI: 10.52711/2349-2988.2026.00002

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