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PROJECT TOPIC: HEPATOCURATIVE AND ANTIOXIDANT EFFECT OF ETHYL-ACETATE AND N-BUTANOL FRACTIONS OF Detarium microcarpum STEM BARK IN CCl4 INDUCED LIVER DAMAGE IN WISTAR RATS

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CHAPTER ONE INTRODUCTION 1.1 Preamble Herbal medicines are herbal preparations produced by subjecting plant materials to extraction,  fractionation, purification, concentration or other physical or biological processes which may be produced for immediate consumption or as a basis for herbal products (WHO, 2001). Notwithstanding the extent of significant advancement in modern medicine in recent decades, plants still make an important contribution to health care. Traditionally they are used worldwide for the prevention and treatment of disease. Herbal plants were prescribed even when their active compounds were unknown because of their effectiveness and relatively low cost (Bhawna and Kumar, 2010). This observation is particularly more relevant to people in the developing countries of the world where the majority of the populations are living in the rural areas.

The liver plays an important role in regulating various physiological processes. It is essential in the body for maintenance, performance and regulating homeostatic functions. It is involved with almost all the biochemical pathways for growth, fight against diseases, nutrient supply, energy provision and reproduction. In addition, it aids metabolism of carbohydrate, protein and fat, detoxification, secretion of bile and storage of vitamins (Ahsan et al., 2009). Because of its central role in drug metabolism, it is the most vulnerable tissue for drug toxicity (Sunil et al., 2012). The role played by the liver in the removal of substances from the portal circulation makes it susceptible to persistent attack by offending foreign compounds, culminating in liver dysfunction (Bodakhe and Ram, 2007). The liver secretes bile, prothrombin, fibrinogen, blood-clotting factors and heparin, a mucopolysaccharide sulfuric acid ester that prevents  blood from clotting within the circulatory system (Bhawna  and Kumar, 2010). Toxic chemicals, xenobiotics, alcohol consumption,  malnutrition, anaemia, medications, autoimmune disorders (Marina, 2006), viral infections (hepatitis A, B, C, D, etc.) and microbial infections (Sharma and.

Ahuja, 1997) are harmful and cause damage to the hepatocytes. Reactive oxygen species (ROS) are continuously generated during metabolic processes to regulate a number of physiological functions essential to the body (Valko et al., 2007). These reactive oxygen species are prone to withdraw electrons from biological macromolecules such as proteins, lipids, nucleic acids in order to gain stability in the biological system. This disruption may be attributed to a number of factors such as the inability of the cells to produce sufficient amounts of antioxidants, nutritional deficiency of minerals or vitamins (Abd Ellah, 2010). When the

production of ROS exceeds the capability of the body to detoxify these reactive intermediates, oxidative stress would develop (Mena et al., 2009). Oxidative stress can be induced by variety of factors such as radiation or exposure to heavy metals and xenobiotics (e.g carbon tetrachloride). This may lead to drastic harm to the body such as membrane damage, mutations due to attenuation of DNA molecules, and disruption to various enzymatic activities in metabolism of the body (McGrath et al., 2001; Valko et al., 2006; Chanda and Dave, 2009).

Medicinal plants are important sources of antioxidants (Rice, 2004). Antioxidants stabilize or deactivate free radicals, often before they attack targets in biological cells (Nunes et al., 2012). Natural antioxidants either in the form of raw extracts or their chemical constituents are very effective in preventing the destructive processes caused by oxidative stress (Zengin et al., 2011).


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