**5. Defense mechanism against free radicals**

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.

#### **5.1. Indirect defense mechanisms**

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