**5.2. Direct defense mechanism**

such as the presence of ROS and RNS as well as antioxidant defense has indicated oxidative damage may be implicated in the pathogenesis of these diseases [29]. Elevated levels of free radicals such as 4-hydroxy-2,3-nonenal (HNE), acrolein, malondialdehyde (MDA) and F2-isoprostanes have been observed in Alzheimer's disease [30, 31]. Oxidative stress also contributes to tissue injury following hyperoxia and irradiation. Evidence from studies have shown oxidative stress to play an important role in the pathogenesis and development of metabolic syndrome related disorders such as obesity, hypertension, diabetes, dyslipidemia etc. as well as in cardiovascular related diseases such as myocardial infarction, aortic valve stenosis, angina pectoris, atherosclerosis and heart failure [32–35]. Cancer is another disease associated with ROS as ROS have been suggested to stimulate oncogenes such as Jun and Fos whose overexpression is directly associated with lung cancer [36]. In lung cancers, p53 can be mutated by ROS thereby losing its function of apoptosis and functioning as an oncogene [37]. Also, the development of gastric cancer has been thought to be due to increase production of ROS and RNS by *Helicobacter pylori* infection in human stomach [29]. Excess ROS in human kidney leads to urolithiasis [29]. ROS have also been reported to damage cellular components in cartilage leading to osteoarthritis [38] and has been shown to be involved in damaging the islets cells of the pancreas [39]. More so, hyperglycemia triggers ROS production in both tubular and mesangial cells of human kidney, making functional and structural changes in

In response to the prevailing level of free radicals both from exogenous and endogenous sources, the human body developed a defense mechanism for protection against cellular damages. These may involve direct and indirect mechanisms put in place by the body.

Firstly, the indirect mechanisms are those mechanisms that do not directly act on the free radicals to eliminate them or convert them to less reactive forms. Rather this indirect system can act in several ways. Certain regulatory mechanisms can control and regulate processes that lead to the endogenous production of ROS [41]. This may be transcriptional control of the enzymes that are involved in the generation of endogenous ROS. Another indirect approach consists of certain molecules and enzymes that are transported to oxidative-damage sites for repair of macromolecules. This may include repair of damage DNA, protein or lipids. For examples damage oxidized adducts of DNA such as 8-hydroxy-2-deoxyguanosine, thiamine glycol, and apurinic can be removed from a nucleotide sequence and replaced by a normal nucleotide base [42]. Also, certain molecules that can donate hydrogen atoms to damaged molecules are also considered as repair compounds. Molecules such as ascorbate or tocopherol can donate hydrogen atom to a fatty acid radical on cell membrane thereby repairing the membrane. Certain natural cellular or surface barriers such as the skin or cell membranes act as indirect defense system against ROS by preventing exogenous ROS from entering the body or preventing certain endogenous ROS from reaching the target macromolecules. Though these indirect defense mechanisms are helpful against ROS, they

glomeruli causing diabetic nephropathy [40].

**5.1. Indirect defense mechanisms**

**5. Defense mechanism against free radicals**

56 Phytochemicals - Source of Antioxidants and Role in Disease Prevention

are usually non-specific and do not act directly on the ROS.

This category of defense system which constitutes the antioxidant system is the most important because they directly act on free radicals either by decomposing, scavenging or converting free radicals to less reactive forms. This defense mechanism constitute two groups; the enzymatic and non-enzymatic antioxidants.
