CHAPTER ONE

INTRODUCTION

1.1.           Background to the Study

The single-dose acute oral toxicity test is used in preliminary evaluation of virtually all substances of suspected biological activity. The test is based on administration of graded dosage of chemical in relation to body mass. Malathion is an organophosphate insecticide which is registered for agricultural uses and for landscape maintenance, vector control, and structural pest control (Cheeseman et al., 2004). This assessment of potential dietary exposures addresses the residues that may occur as a result of agricultural uses of malathion. Organophosphate compounds inhibit the activity of cholinesterase which is an enzyme present in several body tissues and essential for the normal function of nerves.

Selenium belongs to essential microelements. Being a constituent of one of the main antioxidant enzymes – glutathione peroxidase – it is considered to be an antioxidant (Cheeseman et al., 2004). Its possible application as a protective agent against toxic metals and compounds as well as against oxidative stress have already been studied and the outcomes have seemed to be encouraging (Brugh, 2008). Selenium alone or in combination with vitamin E has already been found to prevent oxidative stress in brain of animals exposed to cigarette smoke (Tiwaryand, 2005) chromium (Chowdhury et al., 2005) and mercury (Oser, 2005).

In living systems, oxidation is a basic part of the normal metabolic process, in which reactive oxygen species (hydrogen peroxide and hypochlorous acid) and many free radicals (hydroxyl radical (OH) and superoxide anion) are generated. Rapid production of free radicals may cause alteration in the structure and function of cell constituents and membranes and can results in human neurologic and other disorders such as cancer, diabetes, inflammatory disease, asthma, cardiovascular, neurodegenerative diseases, and premature aging. Therefore, the prevention of the above conditions requires the presence of antioxidants or the free radical scavenging molecules in the body.

1.2.           Statement of the Problem

Exposure of test animals or humans to sufficient dosages of malathion and its primary active metabolite, malaoxon, may result in subsequent signs of toxicity, such as salivation and sweating. Antioxidants are natural or synthetic compounds, produced in vivo, normal cell constituents, ordelivered in diets, whose main function is to fight against oxidative stress (Creighton et al., 2003), being thus able to either delay or prevent the oxidation of substrates, such as proteins, deoxyribonucleic acid (DNA), lipids, DNA mutations, malignant transformations, as well as other parameters of cell damage (Luna, 2008).

Due to the role of hepatocytes in the metabolism of drugs, xenobiotics and endogenous compounds, these cells become the target of reactive oxygen and nitrogen species (ROS/RNS), giving reactive oxygenated metabolites (ROM), requiring, therefore, an important antioxidant defense system (Krzystyniak et al., 2005). Among these antioxidant systems, stands out glutathione (GSH), the most abundant cellular thiol antioxidant, which exhibits numerous and versatile functions and therefore protects cells against toxicity (Prescott et al., 2002).From the above background, the study therefore examine Subacute malathion toxicity and amelioration of selenium and antioxidant on brain histology of male wistar rat

1.3       Aim / Objective of Study

To study the antioxidant effect of selenium on malathion toxicity on the brain of male wistar rat.

1.3.1.  Specific Objectives

Its specific objectives are;

    To evaluate effects of malathion in the brain of male wistar rats.

    To evaluate ameliorating effects of selenium on malathion in the brain of male wistarrats.

    To examine microstructural changes in the brain of male wistar rats administered with malathion.

1.4      Hypotheses

Subacute administration of malathion on male wistar rat may change the enzymatic activities of antioxidant the brain.

1.5       Scope of Study

 The scope of this project work involves the investigation of malathion toxicity and antioxidant activity of selenium on the brain of male wistar rats.

1.6       Significance of the Study

The relevance of this study lies on the importance it provides on the ameliorating effect of selenium regarding the toxicity of malathion in the brain which could be useful to the general public.