**4. Oxidative stress**

Oxidative stress occurs when there is a dysfunction in the overall balance between the production of reactive oxygen and nitrogen species and the antioxidant defense mechanisms (Ceconi *et al.,* 2003; Berk, 2007; Barbosa *et al.,* 2008).

Oxidative stress is believed to play a critical role in the complications and pathophysiology of HIV/AIDS, TB and cardiovascular diseases (Heistad *et al.,* 2009). In the context of oxidative stress in HIV/AIDS and TB, the major vascular ROS is the superoxide anion (O2.-) which is predominantly generated by the NADPH oxidase enzyme (Fortuño *et al*., 2005). Superoxide is normally dismutased to hydrogen peroxide (H2O2) by a family of superoxide dismutase (intracellular Cu/Zn SOD, MnSOD or extracellular Cu/Zn SOD) (Hamilton *et al*., 2004). Hydrogen peroxide is converted into oxygen and water by catalase enzymes or by glutathione peroxidase (GPx) in the presence of reduced glutathione (Hamilton *et al*., 2004; Zalba *et al*., 2006). In the pathophysiological process of oxidative stress, excess superoxide has many effects, superoxide combines with NO to form peroxynitrite. Peroxynitrite is a highly toxic oxidant which causes damage to cells of the vascular wall through oxidation of lipids (lipid peroxidation), proteins (protein nitrosilation) and nucleic acids with superoxide. This causes vascular dysfunction by removing the protective effects of NO (Heistad *et al*., 2009), initiates the development of vascular inflammatory state (Hamilton *et al*., 2004), facilitates the oxidation of LDL, causing development of artherosclerotic lesions (Zalba *et al*., 2006) and triggers apoptotic cell death (Ceconi *et al*., 2003).

Accumulating evidence has suggested that oxidative stress, mainly through lipid peroxidation, represents an important risk factor in the development of cardiovascular

cases (Jargirdar and Zagzag, 1996). The progression and nature of disease may be affected by factors such as conditions that negatively impact on the host immune system (for example, poorly controlled diabetes mellitus, renal failure, chemotherapy, malnutrition or intrinsic host susceptibility (Madebo *et al*., 2003). Host susceptibility has been known to

**3. Reactive oxygen species and reactive nitrogen species and their effects on** 

Reactive oxygen species / reactive nitrogen species (ROS/ RNS) are constantly being formed in living organisms (Ceconi *et al.*, 2003). In the course of oxygen metabolism, 1- 5% of all inhaled oxygen becomes ROS (Berk, 2007). Endogenously, ROS are produced from various sources such as mitochondria, activated macrophages and leucocytes, oxidase enzyme (NADPH), cyclo-oxygenase and lipoxygenase (Zalba *et al.,* 2006). Reactive oxygen species have

radical OH**•**, nitric oxide NO) or as non-free radicals (hydrogen peroxide H2O2, peroxynitrite

physiological and pathophysiological conditions (Fortuño *et al*., 2005; Berk, 2007; Heistad *et al*., 2009). At low concentrations, ROS are involved in normal cell signaling pathways (smooth muscle and endothelial cell growth, apoptosis and survival) and in the remodeling of vessel walls (Fortuño *et al*., 2005; Heistad *et al.,* 2009). At high concentrations, ROS are identified as harmful compounds and constitute an important risk factor for the development of many

Oxidative stress occurs when there is a dysfunction in the overall balance between the production of reactive oxygen and nitrogen species and the antioxidant defense mechanisms

Oxidative stress is believed to play a critical role in the complications and pathophysiology of HIV/AIDS, TB and cardiovascular diseases (Heistad *et al.,* 2009). In the context of oxidative stress in HIV/AIDS and TB, the major vascular ROS is the superoxide anion (O2.-) which is predominantly generated by the NADPH oxidase enzyme (Fortuño *et al*., 2005). Superoxide is normally dismutased to hydrogen peroxide (H2O2) by a family of superoxide dismutase (intracellular Cu/Zn SOD, MnSOD or extracellular Cu/Zn SOD) (Hamilton *et al*., 2004). Hydrogen peroxide is converted into oxygen and water by catalase enzymes or by glutathione peroxidase (GPx) in the presence of reduced glutathione (Hamilton *et al*., 2004; Zalba *et al*., 2006). In the pathophysiological process of oxidative stress, excess superoxide has many effects, superoxide combines with NO to form peroxynitrite. Peroxynitrite is a highly toxic oxidant which causes damage to cells of the vascular wall through oxidation of lipids (lipid peroxidation), proteins (protein nitrosilation) and nucleic acids with superoxide. This causes vascular dysfunction by removing the protective effects of NO (Heistad *et al*., 2009), initiates the development of vascular inflammatory state (Hamilton *et al*., 2004), facilitates the oxidation of LDL, causing development of artherosclerotic lesions (Zalba *et al*.,

Accumulating evidence has suggested that oxidative stress, mainly through lipid peroxidation, represents an important risk factor in the development of cardiovascular

) (Higashi *et al*., 2006). Previous studies have shown the involvement of ROS in

**.**-

, hydroxyl

oxidation ability and are classified either as free radicals (superoxide anion O2

diseases such as cardiovascular diseases (Maxwell & Lip, 1997; Heistad *et al*., 2009).

affect endogenous re-activation and exogenous re-infection by the bacilli.

**biological macromolecules and organs** 

(Ceconi *et al.,* 2003; Berk, 2007; Barbosa *et al.,* 2008).

2006) and triggers apoptotic cell death (Ceconi *et al*., 2003).

ONOO-

**4. Oxidative stress** 

diseases and complications in HIV/AIDS and TB (Waterfall *et al.*, 1997; Ceconi *et al.*, 2003). In fact, lipid peroxidation leads to membrane disruption and release of highly reactive free radicals (such as MDA) which can severely alter the cellular function (Ceconi *et al*., 2003) (Table 1).


*Source:* Murray, 2000

Table 1. Reactions in relation to oxidative stress in blood cells and various tissues.
