THE ROLES OF MOLECULAR MODELING STRATEGIES IN VALIDATING THE EFFECT OF CHRYSIN ON SODIUM ARSENITE-INDUCED CHROMOSOMAL AND DNA DAMAGE

THE ROLES OF MOLECULAR MODELING STRATEGIES IN VALIDATING THE EFFECT OF CHRYSIN ON SODIUM ARSENITE-INDUCED CHROMOSOMAL AND DNA DAMAGE

CHAPTER ONE

1.0 INTRODUCTION

Arsenic is a major environmental toxicant as well as a human carcinogen which is present in large amounts in the environment(Martinez et al., 2011). When ingested, it affect different organs of the body through induction of oxidative damage(Sadiaet al., 2015). Arsenic compounds are ubiquitous in nature and found in the environment via industrial or agricultural processes as well as some medical applications(Aliyu et al., 2013). They are widely used for many industrial purposes, including mining, smelting, herbicidal products, medicines, wine preservatives and electronics(Cheng et al., 2011). Consumption of arsenicals through contaminated water is prevalent in many areas of the world(Aliyu et al., 2013).Arsenic in drinking water is a global environmental health problem(Cheng et al., 2011). Both acute and chronic arsenic exposures have been associated with a higher than normal risk of skin, lung and bladder cancer(Riedmann et al., 2015; Ajani and Olufunke, 2016). It is also known that arsenic interact with other substances, metals inclusive there by potentiating or depressing its effects(Aliyu et al., 2012).

The most common forms of arsenic are water-soluble, arsenite (the trivalent form, As ^III) and arsenate (the pentavalent form, As ^V). Trivalent arsenic is more toxic than pentavalent arsenic and its inorganic forms are more toxic than organic forms(Moktar et al., 2008). After ingestion, the dissolved arsenicals are readily absorbed through the gastrointestinal tract and distributed in the blood to the liver, kidney, spleen, lung and many other organs of the body(Moktaret al., 2008).

Once in the tissues, arsenic exerts its toxic effects through several mechanisms, the most significant of which is, the reversible combination with sulfhydryl‘s groups and inhibition of numerous other cellular enzymes(Muhammad and Ibrahim,2015), especially those involved in cellularglucose uptake, gluconeogenesis and fatty acid oxidation(Kumar, 2015). It also alters multiple cellular pathways including expression of growth factors, suppression of cell cycle checkpoint proteins, promotion of apoptosis, inhibition of DNA repair(Amal et al., 2012), decreasing immunosurveillance and increasing oxidative stress(Sadiaet al., 2015). Arsenic generates reactive oxygen species which also include dimethyl arsenic peroxyl ([(CH₃)₂AsOO])

THE ROLES OF MOLECULAR MODELING STRATEGIES IN VALIDATING THE EFFECT OF CHRYSIN ON SODIUM ARSENITE-INDUCED CHROMOSOMAL AND DNA DAMAGE