**2.2. Sources of free radicals**

their deficiency in electron and instability, attack electron rich centers such as lipid membranes, proteins and nucleic acids thereby damaging cells and tissues in the body. Eventual, the human body is adapted to remove these unstable molecules by a myriad of molecules including certain enzymes collectively known as antioxidants. This antioxidant defense system reduces the level of these free radicals in the body and maintains the homeostatic balance for proper functioning of the body. However, when these reactive species are overwhelming high in the body, it surpasses the capacity of the antioxidant defense system leading to a condition known as oxidative stress. This imbalance between antioxidant and proxidants is characteristic of certain disease conditions such as diabetes, atherosclerosis, cardiovascular diseases, cancer etc. One of the possible remedy for this condition is to supplement the endogenous antioxidant defense system with exogenous antioxidants. Plants have gained considerable interest in recent time in managing oxidative stress related diseases; firstly, because of their ethnopharmacological uses in managing diseases and secondly, due to their richness in phytochemicals which possess antioxidant properties. Hence, this chapter is aimed to give an overview of free radicals, their sources of origin and processes of generation in the environment and body. Also, it will highlight on the various mechanisms of free radical induced cellular damage and the associated diseases due to oxidative stress. The various mechanisms of the antioxidant defense system; both enzymatic and non-enzymatic antioxidants will be described as well as the contribution of plant phytochemicals as antioxidants. Emphasis will be laid on some plants and phytochemicals with antioxidant activities stating their mode of

50 Phytochemicals - Source of Antioxidants and Role in Disease Prevention

scavenging free radicals and prevention of oxidative stress-related diseases.

**2.1. Types of free radicals or reactive oxygen species**

Free radicals are molecular species with unpaired electrons in their atomic orbital capable of independent existence. As such, these radicals are highly reactive and can either extract an electron from molecules or donate an electron to other molecules thus acting as a reductant or an oxidant. Though free radicals have high reactivity, most of them have a very short half-life of less than 10−6 s in biological systems [1]. Some oxygen species known as reactive oxygen species (ROS) are non-reactive in their natural state but are capable of generating free radicals. The idea of free radicals began in chemistry around the beginning of the twentieth century, where chemists initially described them as intermediate organic and inorganic compounds with several suggested definitions. A clear understand of these radicals was then proposed based on the work of Daniel Gilbert and Rebecca Gersham in 1954 [2] in which these radicals were suggested to play important roles in biological environments but also responsible for certain deleterious processes in the cell. Thereafter by 1956, Herman Denham further suggested that these reactive species may play critical roles in physiological process particularly aging process [3]. This hypothesis on the theory of free-radical on aging, inspired numerous research and studies which significantly contributed to the understanding of radicals and other related species such as ROS, reactive nitrogen species (RNS) and non-radical reactive species [4].

ROS are classified into two major categories of compounds which includes the free radicals and the non-reactive radicals. The free radical includes nitric oxide radical (NO•), hydroxyl

**2. Free radicals**

As reviewed from Sultan [8], free radicals can originate either from the environment, physiological processes or endogenous sources.

**External sources:** Certain organic compounds in the atmosphere can react non-enzymatically with oxygen to generate free radicals. Also, reactions initiated by ionizing radiations in the environment can generate free radicals. Thus, some external sources of free radicals include environmental pollutant, cigarette smoke, alcohol, radiations, ozone, ultraviolet light, pesticides, anesthetic, certain drugs, industrial solvents etc.

**Endogenous sources:** This includes processes in living organisms that necessitates enzymatic reactions to generate free radicals. These include reactions involved in the respiratory chain,


**Table 1.** Free radicals and non-reactive radicals of oxygen species.

cytochrome P450 system, phagocytosis and prostaglandin synthesis. Some of these endogenous sources of free radicals generation include reactions in the mitochondria, phagocytes, inflammation, arachidonate pathways, etc. Also, reactions involving iron and other transition metals, peroxisomes, xanthine oxidase, etc. are also endogenous sources of free radicals.

and hydrogen peroxide catalyzed by transition metals [18]. Transition metals generally contain one or more unpaired electrons and thus are capable to transfer a single electron. Iron and copper are the most common transition metals capable of generating free radicals and much implicated in human diseases. As shown by Fenton [19], hydrogen peroxide can react with

Free Radicals and the Role of Plant Phytochemicals as Antioxidants Against Oxidative Stress-Related Diseases

At physiological pH, iron is usually oxidized to Fe3+ and chelates to biological molecules. Thus, for Fenton reaction to occur, iron must be converted to its reduced form Fe2+. Superoxide

<sup>−</sup> → Fe2+ + O2

<sup>−</sup> + H2 O2 → OH<sup>−</sup> + OH• + O2

. (1)

http://dx.doi.org/10.5772/intechopen.76719

53

. (2)

. (3)

iron II (or copper I) to generate hydroxyl radical:

Fe3+ + O2

net reaction (Haber-Weiss reaction):

O2

Fe2+ + H2 O2 → Fe3+ + OH• + OH<sup>−</sup>

radicals can reduce Fe3+ to Fe2+ ions thereby enabling the Fenton reaction.

**Figure 1.** Reactive oxygen species (ROS)-induced oxidative damage. Source: Kohen and Nyska [21].

**Physiological sources:** Certain physiological state or processes like stress, emotion, aging, etc. mental status and disease conditions are also responsible for the formation of free radicals. For example, hyperglycemia is a major source of free radicals in diabetes patients through various metabolic pathways which include increase flux of glucose through the polyol pathway, increase formation of advanced glycation end-products (AGEs) and activation of their receptors, activation of protein kinase C (PKC) isoforms, activation of overactivity of hexosamine pathway and decrease antioxidant defense [9].
