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
|
TABLE
|
TITLE
|
PAGE NO
|
|
4.1
|
The Effect of Different
doses of Cashew (Anacardium occidentale)
on Total Bilirubin Concentration
|
28
|
|
4.2
|
The Effect of Different doses of Cashew nut (Anacardium occidentale)Extract on the
Conjugated Bilirubin
|
29
|
|
4.3
|
The Effect of Different
doses of Cashew (Anacardium occidentale)
extract on AST (Aspartate transferase) Concentration
|
30
|
|
4.4
|
The Effect of Different
doses of Cashew (Anacardium occidentale)
on Alanin transferese (ALT) Concentration
|
40
|
|
4.5
|
The Effect of Different
doses of Cashew (Anacardium occidentale)
on Alkaline Phorsphate (ALP) Concentration
|
41
|
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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