CHAPTER ONE
INTRODUCTION
Humans are continuously exposed to different kinds of chemicals such as food additives, industrial chemicals, pesticides and other undesirable contaminants in the air, food and soil (Osman et al., 2011). Most of these chemicals induce a free radical-mediated lipid peroxidation and alteration of many crucial biological molecules leading to disruption of biomembranes and dysfunction of cell and tissues (Cho et al., 2003; Rahman et al., 2015). In a normal healthy human body, the generation of pro-oxidants in the form of reactive oxygen species (ROS) and reactive nitrogen species (RNS) is effectively kept in check by the various levels of antioxidant defense. However, when it gets exposed to adverse physicochemical, environmental or pathological toxins, this delicately maintained balance is shifted in favour of pro-oxidants resulting in ‘oxidative stress’ (Devasagayam et al., 2004). Under such conditions, supplementation with exogenous antioxidants is required to restore the redox homeostasis in cells (Kunwar and Priyadarsini, 2011). Oxidative stress causes harmful effects to all the body systems and is implicated in the pathogenesis of various diseases including hypertension, atherosclerosis, diabetes mellitus and cancer (Kabel, 2014). There are many biologically active substances in fruits including nutrients and non-nutrients for which protective health effects have been attributed (Sidana et al., 2013). Citrus fruit species are one of the most popularly consumed fruits in the world today; usually consumed as fresh produce or juice, and could be categorized as functional foods containing components shown to have health promoting effects (Sidana et al., 2013; Oboh et al., 2014). Citrus maxima fruit has been used by traditional healers for treating various ailments like ulcers, rheumatism, cancer, diabetes, heart disease and convulsive cough (Bhandurge et al., 2010).
1.1 Oxidative Stress Oxidative stress is a redox disequilibrium in which the pro-oxidant/antioxidant balance is shifted in favour of the pro-oxidants (Videla, 2009). A well maintained balance exists between production of free radicals and their rates of removal by various antioxidant defense mechanisms in a healthy individual (Rekha et al., 2012). Thus each cell is characterized by a particular concentration of reducing species like glutathione (GSH), nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH) stored in many cellular constituents, which determine the redox state of a cell (Kohen and Nyska, 2002). Redox state is the total reduction potential or the reducing capacity of all the redox couples such as GSSG/2GSH, NAD+/NADH and FAD/FADH found in biological fluids, organelles, cells or tissues (Schafer and Buettner, 2001). Redox state not only describes the state of a redox pair, but also the redox environment of a cell. Under normal conditions, the redox state of a biological system is maintained towards more negative redox potential values (Kunwar and Priyadarsini, 2011). However, when ROS and RNS are produced at levels that cannot be counteracted by endogenous antioxidant system, it is shifted towards less negative values resulting in an oxidizing environment which leads to oxidative stress (Fig. 1) (Glantzounis et al., 2005; Kunwar and Priyadarsini, 2011). This condition can lead to the damage of lipids, proteins, carbohydrates, and nucleic acids (Glantzounis et al., 2005). Oxidative stress has been implicated in several human diseases as well as in the ageing process (Kunwar and Priyadarsini, 2011).
