**1. Introduction**

Reactive oxygen species are primarily the result of the by-product of the redox process and may also be produced to initiate intracellular signaling and antimicrobial activity. The general phenomenon is to maintain the ROS level in the cell by antioxidant enzymes and antioxidants molecules present in cells [1]. One of the prime sources of ROS in mammalian cells is the respiratory chain in mitochondria. It's well established that ROS generation is an essential modulator of inflammatory reactions in mammals. The enzyme NADPH oxidase induced the oxidative burst, leading to a dramatic increase in oxygen consumption and increasing the phagocytosis process. Activated macrophage induced the expression of IFN-γ and TNF-α cytokines,

improving NADPH oxidase activity resulting in ROS production, such as oxygenfree radicals (O2 •−) superoxide. The O2 •− species are converted into hydroxyl radical (HO• ), hydrogen peroxide (H2O2), and peroxynitrite (ONOO− ) by spontaneously or enzymatic reaction [2, 3]. Activation of nitric oxide synthase (iNOS) or (NOS2) protein in macrophage stimulates the increased secretion of nitric oxide (NO) and • NO-metabolite levels within the cell. ROS is the first superoxide radicals produced by mitochondria. ROS is a highly reactive oxygen species and does not diffuse quickly from cells since the leading site of ROS production is in the inner mitochondrial membrane. H2O2 is derived from mitochondrial ROS and detoxified by superoxide dismutase. ROS detoxification has been assigned in ROS-generating sites in the cell, such as mitochondria, glycosome, endoplasmic reticulum, and cytosol. Hydrogen peroxide (H2O2) is not considered a free radical by definition since it lacks free electrons. Still, NO is deemed to be free radicals, has also been involved in ROS-mediated damage. However, NO has a dual nature, like as beneficial as well as vicious [4–6].

Aerobic organisms exhibited two major antioxidant defense systems to minimize the ROS-mediated damage occurring due to oxygen-free radicals. The first one is enzymatic defense, and the second is low molecular weight antioxidants such as vitamins and phytochemicals. In general, cells control oxidative stress by three essential antioxidant enzymes which are present in it; (i) Superoxide dismutase is a class of oxidoreductase enzymes that contain metal ions in their active site (Fe or Mn and/or Cu/Zn) and is responsible for converting superoxide anion into H2O2. (ii) glutathione peroxidase is responsible for the reduction of H2O2 into hydroperoxides using glutathione as hydrogen donor, and (iii) catalase is responsible for the breakdown of H2O2 into O2 and H2O [7]. Since the activity glutathione peroxidase is required glutathione as hydrogen donor. Thus, the NADPH-dependent reduction of oxidized glutathione to maintain a steady state of glutathione is needed for GSH activity [1].

Superoxide dismutase catalyzes the dismutation of oxygen free radical to O2 and H2O2 in the cell. SOD enzymes also participate in signaling pathways by controlling ROS action and protecting the cells from the toxic effects of superoxide radicals. Intracellular SODs mainly restrict superoxide action, which harms the cells by damaging the Fe-S cluster-containing enzymes. Extracellular SODs also guard the cells from superoxide released by the host or pathogens. For example, extracellular SODs of microbial pathogens are protected by ROS-mediated killing of host cells. The host cells antioxidant system includes enzymes such as SOD, catalases, and peroxidases [8, 9].
