**6. Protective effects of antioxidants**

Antioxidants are groups of substances which when present at low concentrations, in relation to oxidisable substrates, significantly inhibit or delay oxidative processes while often being oxidised themselves [65]. There exists a balance between their formation and removal (redox state). To maintain an oxido/redox balance, cells protect themselves from the toxicity of excess ROS/RNS in different ways, enzymatic and nonenzymatic antioxidants.

#### **6.1. Relevant HIV antioxidants: Does HIV benefit from their activities?**

There are many biochemical processes that oxidise reduced antioxidant molecules to neutralise free radicals and then restore the antioxidant molecules to a reduced state. In HIV infection, antioxidants serve to aid the CD4 cells in removing the virions by reducing the oxidative stress that develops during HIV infection [66]. Antioxidants are useful to the host for defence and neutralisation of free radicals.

#### *6.1.1. Superoxide Dismutase (SOD)*

Superoxide dismutase (EC 1.15.1.1) destroys the free radical superoxide by converting it to peroxide which is further destroyed by catalase or glutathione peroxidase (GHPX) reaction. It is known that SOD converts the superoxide radical to the less-reactive H202 [67]*.* In humans, the three forms of SOD are cytosolic Cu, Zn-SOD, mitochondria Mn-SOD and extracellular SOD (ECSOD). Generally, SOD catalyses the dismutation of 02 ▪ - by successive oxidation and reduction of the transition metal ion at the active site in a ping-pong-type mechanism with widely acknowledged high reaction rates [68]. Copper-zinc superoxide dismutase (Cu, Zn-SOD) is also known as SOD-I; the active site is constituted by a copper and a zinc atom bridged by a common ligand.

The HIV TAT domain is a regulatory protein of the virus that enhances the efficiency of virus transcription and has been shown to carry exogenous molecules into cells [69], thus can fuse with protein transduction domains (PTDs) for effective cellular cargo delivery [70]. TAT-PTD linked-SOD1 has been shown to be ferried across the cytoplasm and even the mitochondria where superoxide is generated, making TAT-SOD1 a source of intracellular antioxidant [72]. Currently, Qing et al. [73] in 2013 provided evidence that TAT-SOD1 has protective therapeutic activity against ionisation radiation. Conversely, cells actually infected with HIV have been reported to express less Mn-SOD and to lose their ability to induce antioxidant enzyme in response to TNF. Therefore, expression of TAT protein of HIV suppresses cellular Mncontaining superoxide dismutase (Mn-SOD) [74]. Furthermore, the protective nature of Mn-SOD has been demonstrated by several authors; its overexpression provides oxidant protection against AZT or 3TC-induced endothelial dysfunction [75] and against lung cancer radiation therapy [76].
