EVALUATION OF THE HEPATOTOXICITY ACTIVITY OF CASHEW NUT (ANACARDIUM OCCIDENTALE)

ABSTRACT

Hepatotoxicity (from hepatic toxicity) implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease. The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. The aim of this study was to evaluate the hepatotoxicity of cashew nut in albino rats. The administration of the extract to the animal was done for 21 days once daily. The biochemical analysis was performed on serum following the determination of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatise (ALP), Total Bilirubin and Conjugate Bilirubin. A significant (P˂0.05) increase was recorded for total bilirubin concentration when the extract treated groups; 125mg/kg, 250mg/kg, 500 mg/kg, 1000mg/kg were compared to normal control (10.30+0.10a), while the extract treated groups at 125mg/kg, 250mg/kg, 500mg/kg and 1000mg/kg in week 2 and 3 significantly (P˂0.05) increased the conjugated bilirubin, AST (Aspartate transferase), AST (Aspartate transferase) and Alanin transferese (ALT) level when compared with the normal control (5.03+0.15a).  In the present study, the effect of different doses of Cashew extract on Conjugated Bilirubin and AST (Aspartate transferase), AST (Aspartate transferase) and Alanin transferese (ALT) concentration revealed that in week 1 at 125mg/kg group there were no significant (p>0.05) increase when compared to the normal control while other groups in week 1 significantly (p<0.05) increased when compared to the normal control. At lower dosage there was no pathology, while mild portal inflammation was seen at higher dose when compared to the normal control. Conclusively, within the limits of experimental error, the result of this study indicates that weekly administration of ethanol extract of cashew nuts may alter liver status to exhibit toxic effects, particularly at 1000mg/kg body weight of rat. Given the growing use of herbs in a number of ailments, findings from this study suggest that traditional remedies from cashew nuts warrants further investigations.

TABLE OF CONTENTS

Title Page                                                                                                                                i

Declaration                                                                                                                             iii

Certification                                                                                                                           iv

Dedication                                                                                                                              v

Acknowledgements                                                                                                                vi

Table of Contents                                                                                                                   vii

List of Tables                                                                                                                          x

Abstract                                                                                                                                  xi

CHAPTER ONE: INTRODUCTION                                                                                   1

1.0       Background of Study                                                                                                  1

1.1       Aim of Study                                                                                                              3

1.2       Specific Objectives                                                                                                     3

1.3       Statement of Problems                                                                                                3

1.4       Justification of Study                                                                                                  4

CHAPTER TWO: LITERATURE REVIEW                                                                      5

2.2       Causes of Hepatotoxicity                                                                                           5

2.3       Hepatotoxic Drugs                                                                                                      5

2.3.1    Acetaminophen (Paracetamol)                                                                                   5

2.3.2    Nonsteroidal Anti-Inflammatory Drugs                                                                     6

2.3.3    Glucocorticoids                                                                                                          6

2.3.4    Isoniazid                                                                                                                     7

2.3.5    Hydrazine Derivative Drugs                                                                                       7

2.3.6    Natural Products                                                                                                         7

2.4       Drug Metabolism in Liver                                                                                          7

2.4.1    Genetic Diversity                                                                                                        8

2.4.2    Change in Enzyme Activity                                                                                       9

2.4.3    Competitive Inhibition                                                                                               9

2.5       Mechanism of Hepatotoxicity                                                                                    9

2.5.1    Pathophysiologic Hepatic Damage                                                                            10

2.6       Models of Hepatotoxicity                                                                                           11

2.6.1    Galactosamine Induced Liver Necrosis                                                                      12

2.6.2    Paracetamol Induced Hepatotoxicity                                                                         12

2.6.3    Antitubercular Drugs Induced Hepatotoxicity (rifampicin,

            isoniazid and pyrazinamide)                                                                                      12

2.6.4    Carbontetrachloride Induced Liver Fibrosis in Rats                                                  14

2.6.5    Alkyl Alcohol Induced Liver Necrosis in Rats                                                          15

2.6.6    Ranitidine Induced Hepatotoxicity                                                                            16

2.6.7    Thioacetamide Induced Hepatotoxicity                                                                     16

2.7       Common Liver Function and Diagnostic Tests                                                          17

2.7.1    Serum Glutamate Oxaloacetate Transaminase (SGOT) Test                                     17

2.7.2    Serum Glutamate Pyruvate Transaminase (SGPT) Test                                            17

2.7.3    Serum Alkaline Phosphates Test                                                                                17

2.7.4    Serum Total Protein and Albumin Test                                                                      18

2.7.5    Serum Total and Direct Bilirubin Test                                                                       18

2.7.6    Urine Bilirubin                                                                                                           18

2.7.7    Urobilinogen                                                                                                               19

2.7.8    Serum Lipid Profile Test                                                                                            19

2.7.9    Lactic Dehydrogenase (LDH) Test                                                                            19

2.7.10  Ascorbic Acid Content in Urine                                                                                 20

2.7.11  Bromosulphthaline Clearance Test                                                                            20

2.7.12  Superoxide Dismutase (SOD)                                                                                    20

2.7.13  Glutathione (GSH)                                                                                                      20

2.7.14  Lipid Peroxidation                                                                                                      21

2.7.15  Glutathione Peroxidase                                                                                               21

CHAPTER THREE: MATERIALS AND METHODS                                                      22

3.1       Equipments and Apparatus                                                                                         22

3.2       Reagents/Chemicals                                                                                                   22

3.3       Preparation of Plant Extract                                                                                       23

3.4       Experimental Animals                                                                                                23

3.5       Experimental Design                                                                                                  23

3.6       Methods for Biochemical Parameters                                                                        24

3.6.1    Determination of Total Bilirubin Test (TBIL)                                                           24

3.6.2    Determination of Alanine Transaminase Test (ALT)                                                25

3.6.3    Determination of Aspartate Transaminase Test (AST)                                              25

3.6.4    Determination of Alkaline Phosphatase Test (ALP)                                                  26

3.7       Histopathological Examination                                                                                  26

3.7.1    Slide Examination                                                                                                      27

CHAPTER FOUR

4.0       Results and Discussion                                                                                               28

4.1       Histopathology Result                                                                                                33

4.2       Discussion                                                                                                                   38

CHAPTER FIVE: CONCLUSION AND RECOMMENDATION                                     43

5.2       CONCLUSION                                                                                                           43

5.1       Discussion                                                                                                                   43

5.2       Conclusion                                                                                                                  43

            References

LIST OF TABLES

CHAPTER ONE

INTRODUCTION

1.0       BACKGROUND OF STUDY

Hepatotoxicity (from hepatic toxicity) implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease (Kumar et al., 2002). The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses and sometimes even when introduced within therapeutic ranges, may injure the organ. Other chemical agents, such as those used in laboratories and industries, natural chemicals (e.g., microcystins) and herbal remedies can also induce hepatotoxicity (Kumar et al., 2002). Chemicals that cause liver injury are called hepatotoxins. More than 900 drugs have been implicated in causing liver injury (Friedman et al., 2003) and it is the most common reason for a drug to be withdrawn from the market. Hepatotoxicity and drug-induced liver injury also account for a substantial number of compound failures, highlighting the need for toxicity prediction models (e.g. DTI), (Dixit, 2019) and drug screening assays, such as stem cell-derived hepatocyte-like cells, that are capable of detecting toxicity early in the drug development process (Greenhough and Hay, 2012). Chemicals often cause subclinical injury to the liver, which manifests only as abnormal liver enzyme tests. Drug-induced liver injury is responsible for 5% of all hospital admissions and 50% of all acute liver failures (McNally and Peter, 2006).

The cashew nut liquid is a natural source of phenolic compounds that contribute to its antioxidant, antifungal, antibacterial, larvicidal, and nongenotoxic effects in prokaryotic and eukaryotic cells (Acevedo et al., 2006).

The liver is a vital organ and its strategic location and multidimensional functions support almost every other organ in the body. Liver is also the main organ for metabolism and elimination of drugs (Singh et al., 2012). At the same time liver is prone to many diseases like allergy to food and involves immune system as well. The bare area of the liver is a site that is vulnerable to the passing of infection from the abdominal cavity to the thorax (Singh et al., 2012). Hepatitis is caused due to viruses, poisons, autoimmunity and can also result from non-alcoholic fatty liver disease connected with obesity and steatosis. Hepatic encephalopathy is caused by accumulation of toxins in the bloodstream that are normally removed by the liver. Liver damage can also be caused by drugs, particularly anti-tubercular drugs, general anesthetics, paracetamol and some anti-cancer drugs (Singh et al., 2012).

Liver can sometimes be damaged by some chemicals called hepatotoxins, such as galactosamine and chloroform (Mohan, 2002). Moreover, steroids, vaccines and antiviral drugs which are used as therapy for liver diseases, may produce adverse effects especially after chronic administration. There are more than 900 drugs that can lead to hepatotoxicity and is one of the important reasons for some of the drugs withdrawn from market. Liver toxicity not only occurs from direct toxicity of the primary compound but also from reactive metabolite or immunologically-mediated response. This can affect hepatocytes, biliary epithelial cells and liver vasculature (Singh et al., 2011). Hepatotoxic response generated by chemicals depends upon the concentration of the toxicant, distinctive expression of enzymes and concentration gradient of substance in blood covering the acinus (Kedderis, 2006).  Traditional healing practices are now wide spread amongst about 80% of the developed countries population and often termed alternative or complementary medicine. In view of the scarcity of reliable liver-protective drugs in modern medicine, hepatoprotective drugs from plant sources seem to have attractive alternatives. In order to validate the potentials of these compounds, their efficacy in experimental models of hepatic dysfunction needs to be investigated.

1.1       AIM OF STUDY

This study is aimed at evaluating hepatotoxicity of cashew nut in an albino rat.

1.2       SPECIFIC OBJECTIVES

·       To obtain methanol extract of cashew nut

·       To investigate the effect of cashew nut extract on liver function of wistar albino rats and on the liver indices

·       To evaluate the effect of cashew nut extract on the histology of the liver.

1.3       STATEMENT OF PROBLEMS

Drug-induced hepatotoxicity is common and nearly all classes of medications can cause hepatotoxity. Most cases of hepatotoxicity are benign, and improve after drug withdrawal. It is important to recognize and remove the offending agent as quickly as possible to prevent the progression to chronic liver disease and/or acute liver failure. There are no definite risk factors for hepatotoxity, but pre-existing liver disease and genetic susceptibility may predispose certain individuals. Although most patients have clinical symptoms that are identical to other liver diseases, some patients may present with symptoms of systemic hypersensitivity. Treatment of drug-induced hepatotoxity consists of rapid drug discontinuation and supportive care targeted to alleviate unwanted symptoms. There have also been reports of severe complication and co-morbidities associated with hepatotoxity, and most of the current drugs in use have failed to effectively minimize or eradicate these comorbidities and complications associated with hepatotoxity. In view of the foregoing, there is need to seek alternatives to the synthetic drugs. The evaluation of hepatotoxicity effect of cashew nut then very imperatively.

1.4       JUSTIFICATION OF STUDY

A common misconception is that the use of natural substances in a variety of herbal preparations, concentrations and supplements cannot present toxic events. However, although there is a paucity of published data on toxicity and safety profile of medicinal plant remedies, a few reports suggest their adverse effects on some organs, including liver. In previous works, the nuts, kernels and leaf extract of cashew tree have demonstrated nutritional and biochemical health benefits. In addition, extracts from cashew nut have also been reported with favourable effects in animal models. However, the evaluation of its safety and toxic potential is important and this is currently sparsely available.

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