Sources of Free Radicals

Free radicals are the products of normal cellular metabolism. A free radical can be defined as an atom or molecule containing one or more unpaired electrons in a valency shell or outer orbit and is capable of independent existence. The odd number of electron(s) of a free radical makes it unstable, short-lived, and highly reactive. Because of their high reactivity, they can abstract electrons from other compounds to attain stability. Thus the attacked molecule loses its electron and becomes a free radical itself, beginning a chain reaction cascade that finally damages the living cell]. Both ROS and RNS collectively constitute the free radicals and other nonradical reactive species. The ROS/RNS play a twofold job as both beneficial and toxic compounds to the living system. At moderate or low levels ROS/RNS have beneficial effects and involve various physiological functions such as immune function (i.e. defense against pathogenic microorganisms), several cellular signaling pathways, mitogenic response, and redox regulation. But at higher concentrations, both ROS, as well as RNS, generate oxidative stress and nitrosative stress, respectively, causing potential damage to the biomolecules.

These reactive oxygen species can be combated with the involvement of antioxidants of both exogenous and endogenous origins. Antioxidants are a group of substances that, when present at a low concentration of oxidizable substrates, significantly inhibit or delay oxidative processes, while often being oxidized themselves. Antioxidants can be better understood by having information about their natural reactivity of reactive oxygen species or free radicals.

What are free radicals

Chemical species having one or more unpaired electrons are called free radicals. Homolytic bond fission leads to the formation of free radicals. The free radicals are odd electron molecules and are highly reactive. Free radicals are paramagnetic in that they possess a small permanent magnetic moment due to the presence of unpaired electrons. This property is used for the detection of the presence of free radicals.

Reactive oxygen species and free radicals

Reactive oxygen species is a collective term that includes all reactive forms of oxygen, including both radical and nonradical species that participate in the initiation and/or propagation of chain reactions. Free radicals represent a class of highly reactive intermediate chemical entities whose reactivity is derived from the presence of unpaired electrons in their structure, which is capable of independent existence for very brief intervals of time. Free radicals and other reactive species are derived either from normal essential metabolic processes or from external sources, such as exposure to x-rays, ozone, cigarette smoking, air pollutants, industrial chemicals, etc.

Sources of free radicals

Free radicals and other ROS are derived either from normal essential metabolic processes in the human body or from external sources such as exposure to X-rays, ozone, cigarette smoking, air pollutants, and industrial chemicals. Free radical formation occurs continuously in the cells as a consequence of both enzymatic and nonenzymatic reactions. Enzymatic reactions, which serve 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 be formed in nonenzymatic reactions of oxygen with organic compounds as well as those initiated by ionizing reactions.

Free radicals are generated internally through the following sources.

• Mitochondria

• Inflammation

• Exercise

• Phagocytosis

• Peroxisomes

Free radicals are found externally in the following sources.

• Environmental pollution

• Cigarette smoke

• Radiation

• Drugs and pesticides

Mitochondria 

Most of the intracellular ROS are derived from mitochondria. The superoxide radicals are produced at two major sites in the electron transport chain, namely complex I (NADH dehydrogenase) and complex III (ubiquinone cytochrome c reductase). The transfer of electrons from complex I or II to coenzyme Q or ubiquinone (Q) results in the formation of a reduced form of coenzyme Q (QH2). The reduced form QH2 regenerates coenzyme Q via an unstable intermediate semiquinone anion (∙Q–) in the Q-cycle. The formed ∙Q–immediately transfers electrons to molecular oxygen leading to the formation of superoxide radical. The generation of superoxide is non-enzymatic and therefore higher the metabolic rate, the greater the production of the ROS.

Mitochondria have been considered to be mediators of cell metabolism involved in important life processes, such as aging, cell death, and persistent chronic diseases, in addition to their main function of producing ATP. Chronic diseases cause mutations or deletions in the mitochondrial genome (mt genome), which is believed to accumulate damage from long-term oxidative stress. Because mitochondrial DNA (mtDNA) encodes 13 genes for proteins that comprise a part of the electron transport chain (ETC), damage to these genes causes ETC impairment. Treatment with ETC inhibitors (rotenone, 3- nitropropionic acid, thenoyltrifluoroacetone, antimycin A, and sodium cyanide) generates increased intracellular reactive oxygen species (ROS). A significant increase in ROS was also observed in cells lacking mtDNA and mtDNA-deleted cells compared with their parental cells, although no increase was observed in cybrids. Furthermore, cells transfected with cDNA encoding manganese superoxide dismutase had decreased levels of ROS. These results suggest that more ROS are generated from mitochondria in cells that have the ETC impaired either by inhibition or damage to the mtDNA.

Inflammation

The role of free radicals can be found in the inflammatory process which is a complex process resulting in many human diseases. Inflammations are mainly divided into acute and chronic inflammation depending on various inflammatory processes and cellular mechanisms. In recent years there has been a great deal of attention to the field of free radical chemistry. Free radicals such as reactive oxygen species and reactive nitrogen species are generated by our body by various endogenous systems, exposure to different physiochemical conditions, or pathological states. The purpose of the present review is to mention the role of free radical formation in the most common inflammatory processes in animals. Continued oxidative stress can lead to chronic inflammation, which in turn could mediate the most chronic diseases including cancer, diabetes, cardiovascular, neurological, and pulmonary diseases. ROS and NRS are well recognized for playing a role as deleterious species. ROS and RNS are normally generated by tightly regulated enzymes, such as NO synthase and NADPH oxidase isoforms, respectively. The detrimental effect of free radicals causing health damage is termed oxidative stress and nitrosative stress. Overproduction of ROS results in oxidative stress, a deleterious process that can damage cell structures, including lipids, proteins, and DNA.

Conclusion

If free radicals overwhelm the body’s ability to regulate them, a condition known as oxidative stress. Free radicals can steal electrons from lipids, proteins, and DNA causing them damage. Antioxidants in the foods we eat can neutralize the unstable molecules, reducing the risk of damage. Because of their high reactivity, they can abstract electrons from other compounds to attain stability.

Free radicals are generally produced as a result of the influence of external factors, such as pollution, cigarette smoke, or internally, as a result of intracellular metabolism if the antioxidant mechanisms are overwhelmed.