*3.2. Oxidative Stress*

Chemical species with one or more unpaired electrons are called free radicals. In biological systems, the term "free radicals" refers to reactive oxygen species (ROS). Major ROS include O2•−, H2O2, and •OH [72]. In addition to ROS, reactive nitrogen species (RNS), including peroxynitrite (NO3 −), NO, and S-nitrosothiols, also contribute to the generation of oxidative stress. Both ROS and RNS arise as intermediates in several metabolic processes and are specifically produced as part of the cellular defense against invasive pathogens. Free radicals also regulate many processes, including cellular growth, glucose metabolism, and proliferation [73].

Apart from certain beneficial effects, free radicals induce various deleterious effects. In a non-specific manner, ROS can react on significant biomolecules, which leads to deleterious effects like a loss of enzyme activity, genetic mutations and permeability alterations in the cell membrane, and RNS-induced protein *S*-nitrosylation [74]. Because DNA is constantly attacked by the free radicals, around 75,000 to 100,000 DNA damage events might occur in each cell per day. •OH is the most reactive species and interacts with all biological molecules, including the C-8 position of guanine to form 8-hydroxyguanine, which is one of the most frequently found oxidized bases in DNA [75].

An increase in the free radical concentration in the body can cause subsequent oxidative and cellular damage to lipids, proteins, RNA, and DNA [76]. The leaf extract of *M. koenigii* has recently been shown to possess potential antioxidant activity and protection against oxidative stress induced in diabetes [77]. The aqueous leaf extract of *M. koenigii* has been shown to reduce lipid peroxidation and decrease cellular damage, thereby protecting the liver from ethanol-induced toxicity [31]. Khan et al. reported the antioxidant effect and preventive effect of curry leaves in cadmium-induced oxidative stress, cardiac tissue damage, and alterations in normal cardiac functions in rats [78]. Mitra et al. reported the heavy metal chelating activity of an *M. koenigii* leaf extract. They found that there was a significant decrease in the tissue cadmium level when the rats were pre-treated with the *M. koenigii* leaf extract before cadmium administration [79].
