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CHAPTER ONE

INTRODUCTION

1.1 Background of the Study

Liver damage and dysfunction represent significant health issues globally, often resulting from various factors, including viral infections, alcohol consumption, and exposure to toxic substances. Carbon tetrachloride (CCl₄) is a widely studied hepatotoxin that induces liver damage in experimental models, serving as a valuable tool for understanding the underlying mechanisms of liver injury and potential therapeutic interventions (Bello et al., 2019). The liver plays a critical role in metabolic processes, detoxification, and synthesis of essential proteins. Thus, any compromise in liver function can have profound implications on overall health, leading to conditions such as liver cirrhosis, fatty liver disease, and hepatocellular carcinoma (Khan et al., 2020).

Alstonia boonei, commonly known as the “God’s Tree,” is a medicinal plant indigenous to tropical regions, particularly in West Africa. Its bark has been traditionally used in herbal medicine to treat various ailments, including fever, malaria, and digestive disorders (Adeyemi et al., 2018). Recent pharmacological studies have highlighted the antioxidant, anti-inflammatory, and hepatoprotective properties of Alstonia boonei extracts, suggesting its potential utility in ameliorating liver damage caused by various insults, including CCl₄ (Ijeh et al., 2020). The active phytochemicals present in Alstonia boonei, such as alkaloids, flavonoids, and tannins, are thought to contribute to its hepatoprotective effects through mechanisms that mitigate oxidative stress and inflammation (Adesina et al., 2021).

The relationship between oxidative stress and liver injury has been extensively documented, with reactive oxygen species (ROS) playing a pivotal role in the pathogenesis of liver diseases (Gonzalez et al., 2018). CCl₄ metabolism in the liver generates free radicals that cause lipid peroxidation, protein damage, and apoptosis of hepatocytes, leading to inflammation and fibrosis (Nduka et al., 2019). Given the high levels of oxidative stress associated with CCl₄-induced liver injury, the therapeutic potential of natural antioxidants, such as those found in Alstonia boonei, has gained increasing attention.

Studies indicate that Alstonia boonei extracts can significantly reduce liver enzyme levels, indicating a protective effect against hepatotoxicity (Ayo et al., 2020). For instance, research has demonstrated that oral administration of Alstonia boonei extract can decrease serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in CCl₄-treated animals, signifying improved liver function (Okwu et al., 2021). Moreover, the histopathological analysis of liver tissues from treated animals reveals a reduction in necrosis and inflammatory cell infiltration, further supporting the hepatoprotective effects of this plant extract (Adelakun et al., 2022).

While the existing body of literature emphasizes the potential of Alstonia boonei in the management of liver damage, there remains a gap in understanding the specific mechanisms through which it exerts its protective effects. Furthermore, most studies have been conducted on various animal models, necessitating a focused investigation on its impact on liver function in male rabbits subjected to CCl₄-induced liver damage. Thus, the present study aims to elucidate the effect of Alstonia boonei stem bark extract on liver function, providing insights into its therapeutic applications in managing hepatotoxicity.

The exploration of Alstonia boonei's hepatoprotective properties is particularly relevant in light of the increasing incidence of liver diseases, which impose substantial health burdens worldwide. By investigating the efficacy of this traditional medicinal plant in a controlled experimental setup, the study seeks to contribute to the growing body of knowledge regarding natural remedies for liver health. Moreover, the findings of this research may provide a scientific basis for the incorporation of Alstonia boonei into pharmacological formulations aimed at liver protection, potentially offering a safer alternative to synthetic hepatoprotective agents.

In conclusion, the current study aims to investigate the effect of Alstonia boonei stem bark extract on liver function in CCl₄-induced liver damage in male rabbits. By bridging the gap in existing literature, this research will contribute to a better understanding of the therapeutic potential of Alstonia boonei, promoting its use in complementary and alternative medicine for liver health.

1.2 Statement of the Problem

The rising incidence of liver diseases poses significant challenges to public health, particularly in regions where hepatotoxic exposures are prevalent. The use of synthetic hepatoprotective agents is often accompanied by adverse effects, leading to a growing interest in alternative therapeutic approaches using natural products. Despite the promising hepatoprotective properties of Alstonia boonei, there is insufficient scientific evidence concerning its efficacy and mechanisms of action in mitigating liver damage induced by CCl₄. This study seeks to address this knowledge gap by investigating the effect of Alstonia boonei stem bark extract on liver function in male rabbits subjected to CCl₄-induced liver injury.

1.3 Objectives of the Study

The main objective of this study is to determine the hepatoprotective effects of Alstonia boonei stem bark extract on liver function in CCl₄-induced liver damage in male rabbits.

Specific objectives include:

i. To evaluate the impact of Alstonia boonei stem bark extract on liver enzyme levels in CCl₄-induced liver damage.

ii. To determine the histopathological changes in the liver tissue of rabbits treated with Alstonia boonei extract.

iii. To find out the effect of Alstonia boonei extract on oxidative stress markers in male rabbits with CCl₄-induced liver damage.

1.4 Research Questions

i. What is the effect of Alstonia boonei stem bark extract on liver enzyme levels in male rabbits with CCl₄-induced liver damage?

ii. What is the histopathological outcome of Alstonia boonei extract treatment in the liver tissue of rabbits exposed to CCl₄?

iii. How does Alstonia boonei extract influence oxidative stress markers in male rabbits subjected to CCl₄-induced liver damage?

1.5 Significance of the Study

This study is significant for several reasons. Firstly, it seeks to contribute to the existing body of knowledge regarding the hepatoprotective properties of Alstonia boonei, thereby supporting its traditional use in managing liver disorders. The findings will provide empirical evidence on the effectiveness of this plant extract, which may promote its integration into clinical practice for liver health management. Secondly, this research will offer insights into the underlying mechanisms through which Alstonia boonei exerts its protective effects, potentially leading to the development of novel therapeutic strategies for preventing and treating liver damage. Finally, the outcomes of this study may pave the way for further research on the pharmacological applications of Alstonia boonei and similar medicinal plants in liver health.

1.6 Scope of the Study

The scope of this study is confined to the evaluation of the hepatoprotective effects of Alstonia boonei stem bark extract on liver function in male rabbits subjected to CCl₄-induced liver damage. The research will primarily focus on assessing liver enzyme levels, histopathological changes in liver tissue, and oxidative stress markers. The study will utilize a controlled experimental design, with specific attention given to the methodology employed in the extraction of Alstonia boonei and the administration of CCl₄. The findings of this study will be limited to the specific parameters assessed and may not be generalizable to other species or types of liver injury.

1.7 Limitations of the Study

Several limitations may affect the outcomes of this study. Firstly, the experimental design is restricted to male rabbits, which may limit the applicability of the findings to other genders or species. Additionally, the study will focus exclusively on the effects of Alstonia boonei stem bark extract and may not account for the potential interactions with other dietary or environmental factors influencing liver function. Furthermore, the duration of the study may not capture the long-term effects of Alstonia boonei extract on liver health. Finally, variations in individual responses to treatment could introduce variability in the results, highlighting the need for caution when interpreting the findings.

1.8 Definition of Terms

Alstonia boonei: A medicinal plant known for its traditional use in treating various ailments, particularly in West Africa. Its stem bark is rich in phytochemicals that exhibit potential hepatoprotective effects.

Carbon Tetrachloride (CCl₄): A chemical compound commonly used in laboratories and industries, known for its hepatotoxic properties when metabolized in the liver, leading to oxidative stress and liver damage.

Hepatoprotection: The ability of a substance to prevent damage to the liver or promote its repair following injury.

Oxidative Stress: An imbalance between the production of reactive oxygen species and the body’s ability to detoxify them, leading to cellular damage.

Hepatotoxicity: The occurrence of liver damage caused by chemicals, drugs, or other substances.

Liver Enzymes: Enzymes such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) that are released into the bloodstream during liver injury, serving as biomarkers for assessing liver function.

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