ABSTRACT
The
potential effect of methanolic extract of the leaves of Acalypha wilkesiana on the weight of wistar rats was investigated.
Calculated amount of methanolic leaf extract of Acalypha Wilkesiana were constituted in distilled water from the
stock solution to give doses of 500,500 and 1000 mg/kg body weight of
paracetamol, vitamin C and leaf extract respectively and administered to the
various groups (A, B, C and D). Prior to the administration of methanolic leaf
extract of Acalypha Wilkesiana at
every interval of seven days, the body weights of the animals were recorded. The acute administration of the aqueous leaf extract
of Acalypha
wilkesiana did not result in obvious
signs of morphological changes or death of male rats throughout the
experimental period. A significant difference (P>0.05) was
obtained in the average body
weight of animals administered with the extract as compared with the
paracetamol treated group. The organ weight
also elucidated no significant differences (P<0.05) in the kidney,
brain, heart, lung and pancreas except for the liver where there was an increase
in the weight of the liver treated with extract as compared to that of the rats
treated with paracetamol. From the results obtained it is shown that the
extract altered the weight of the liver and is therefore not hepatoprotective,
this extract should undergo further investigation before oral administration is
recommended.
TABLE OF CONTENTS
Title Page.............................................................I
Certification........................................................Ii
Dedication................................................................Iii
Acknowledgement...........................................Iv
Table of
Content........................................................V
Abstract................................................................Vi
CHAPTER ONE
INTRODUCTION
1.1 Medicinal
Plants.....................................................................1
1.1.1 Acalypha
Species.................................................................2
1.1.2 Acalypha
Wilkesiana............................................................4
1.2 Paracetamol..............................................................................7
1.2.1 Medical Uses Of
Paracetamol..................................................8
1.2.2 Paracetamol Induced
Hepatoxicity........................................9
1.2.3 Mechanism Of Action Of Paracetamol In Hepatoxicity.............10
1.3 Weight.....................................................................................12
1.3.1 Weight Determination.........................................................12
1.3.2 Weight Associated
Diseases................................................12
1.4 Organ Weight Of Rats.........................................................13
1.4.1 liver.....................................................................................13
1.4.2 Kidney.................................................................................17
1.4.3 Heart.................................................................................18
1.4.4 Brain...................................................................................18
1.4.5 Testes................................................................................19
1.4.6 Lungs.................................................................................20
1.5 Objective Of
Study...................................................................20
CHAPTER TWO
MATERIALS AND METHODS
2.1 Materials.................................................................................21
2.1.1 Plant Materials For
Analysis.................................................21
2.1.2 Laboratory Animals.................................................................22
2.2 Instrument Used......................................................................22
2.3 Methods..............................................................................23
2.3.1 Experimental Animals And
Procedure.............................24
2.4 Statistical Analysis..................................................................25
CHAPTER THREE
RESULTS...............................................................................................26
DISCUSSION..........................................................................................27
CHAPTER FOUR
CONCLUSION........................................................................................29
REFRENCES...........................................................................................30
CHAPTER ONE
INTRODUCTION AND LITERATURE
REVIEW
1.1 MEDICINAL PLANTS
The
use of plants for healing purposes has always been part of human culture and it
is getting increasingly popular in Nigeria. Acalypha
wilkesiana is one of several medicinal plants used in Nigeria and it has various ethno
botanical uses. Acalypha wilkesiana belongs to the family Euphorbiaceae. It is propagated by stem
cuttings at any time of the year. Under ideal conditions, it grows as a
spreading evergreen shrub with upright branches that tend to originate near the
base and can get up to 3.1 m tall with a similar spread. It has leafs (12.7-
20.3 cm long) that are alternate, elliptic to oval, serrate and
multi-coloredans small inconspicuous flowers (10.2-20.3 cm) that hangs in
catkin-like racemes beneath the foliage (Al-attar, 2010).
In
some parts of southern Nigeria, the use of diuretics in the treatment of
hypertension has been traditionally substituted for aqueous leaf extract of Acalypha wilkesiana. Acute changes in body mass over a short time period can
frequently be assumed to be due to body water loss or gain; 1 ml of water has a
mass of 1 g and therefore changes in body mass can be used to quantify water
gain or loss. Over a short time period, no other body component will be lost at
such a rate, making this assumption possible (Shirreffs, 2003), thus weight
parameters were evaluated and used as makers of hydration status of the male
Wistar rats.
1.1.1 ACALYPHA SPECIE
Kingdom: Plantae
Order:
Malpighiales
Family: Euphorbiaceae
Subfamily:
Acalyphoideae
Tribe: Acalypheae
Subtribe:
Acalyphinae
Genus Acalypha
Acalypha
is a plant genus of the family
Euphorbiaceae. It is the sole genus of the subtribe Acalyphinae. With 450 to 500 species of shrubs, trees and annuals,
the genus is only behind Euphorbia, Croton and Phyllanthus in terms of
Malpighiales diversity. The common name is copperleaf, three-seeded mercury or
cat's tail (Pax et al, 1924). These
plants are mostly tropical or subtropical, with a few representatives in
temperate zones. The Americas
contain two thirds of the known species, distributed from southern United States to Uruguay
and northern Argentina.
Several species, such as Acalypha
ecuadorica, Acalypha eggersii and
Acalypha raivavensis are nearly
extinct, and the St. Helena Mountain Bush or "stringwood" Acalypha rubrinervis already is hispida
(chenille plant, red-hot cat's tail), cultivated as a houseplant because of its
colourful and texturally exciting flowers, has gained the Royal Horticultural
Society's Award of Garden Merit. (Grubben et
al, 2004), as has Acalypha
hispaniolae (Hispaniola cat's tail). Others are grown for their foliage and
a number of cultivars have been developed, such as Acalypha wilkesiana 'Obovata
Cristata' and Acalypha wilkesiana
Acalypha wilkesiana “Hoffmannii'. Acalypha bipartita is eaten as a vegetable in some parts of Africa.
1.1.2 ACALYPHA WILKESIANA
Kingdom: Plantae
Order: Malpighiales
Family: Euphorbiaceae
Genus: Acalypha
Species: Acalypha wilkesiana
Binomial name:
Acalypha wilkesiana
Acalypha wilkesiana
is an evergreen shrub. It grows 3 m high and spreads 2 m across. The stem is
erect with many branches. The branches have fine hairs. It has a closely
arranged crown. The leaves are coppery green with red splashes of colour. This
gives them a mottled appearance. The leaves are large and broad with teeth
around the edge. They can be 10–20 cm long and 15 cm wide. The leaves
are finely hairy. They can be flat or crinkled. The flowers are reddish in
spikes at the end of branches. They have separate male and female flowers on
the same plant. The male flowers are in long spikes which hang downwards while
the female flowers are in short spikes. They do not show up easily as they are
often hidden among the leaves. The flower stalks are 10–20 cm long. A
tropical and subtropical plant which grows naturally in Vanuatu. It occurs in the Pacific Islands. It prefers light well drained
soil. It suits a protected shady position. It is damaged by both drought and
frost. It needs a minimum temperature above 10°C. It suits hardiness zones
9-12. Acalypha wilkesiana ointment is
used to treat fungal skin diseases (Oyelami et
al, 2003) carried out a
non-comparative study to evaluate the safety and efficiency of Acalypha wilkesiana ointment using 32
Nigerians with mycological as well as clinical evidence of mycoses. The
ointment successfully controlled the mycoses in 73.3% of the affected patients.
It was very effective in treating Pityriasis
versicolor, Tinea pedia and Candida intetrigo, with 100% cure
(Oyelami et al, 2003) concluded that Acalypha wilkesiana ointment can be used
to treat superficial mycoses (Akinyemi et
al, 2005) evaluated crude extracts from six important medicinal plants,
namely: Phylantus discoideus, Ageratum
conyzoides, Terminalia avicennioides, Bridella ferruginea, Acalypha wilkesiana and Ocimum
gratissimum, to find activity against methicillin resistant Staphylococcus aureus (MRSA. Water and
ethanolic extracts of these plants were obtained locally. MRSA strains isolated
from patients were used. Both ethanolic and water extracts showed effects on
MRSA. Minimum bactericidal concentration (MBC) and minimum inhibition
concentration (MIC) of these plants ranged from 30.4-37.0 mcg/ml and 18.2-24.0
mcg/ml respectively. A high MBS value was found in two plants and the other
four contained traceable amounts of anthraquinones. This study provided
scientific support for the use of Acalypha wilkesiana, T. avicennioides, O. gratissimum and P. discoidens against MRSA based diseases. A. conyzoides and B. ferruginea
were unresponsive against the MRSA strains (Oyelami et al, 2003).
1.2
PARACETAMOL
Fig 1:
structure of paracetamol
Paracetamol
(called acetaminophen in the USA)
is one of the most commonly used non-narcotic analgesic and antipyretic agents.
It has relatively weak anti-inflammatory activity. Paracetamol is reported to
be selective inhibitor of Cox 3 (cyclooxygenase). Although some reported
evidence show that paracetamol has significant anti- inflammatory action
(Granberg et al, 1999). Paracetamol
toxicity is one of the most common causes of poisoning worldwide. In the United States and United Kingdom it is the most
common cause of acute liver failure. Paracetamol was the fourth most common
cause of death following self-poisoning in the United Kingdom in 1989;
(karthikeyan et al., 2005), yet it is
still one of the most common analgesic and antipyretic drugs often used around
the world to treat pains and mild feverish conditions. As far as this is true,
it is also one of the major causes of liver damage such as liver necrosis.
Traditionally, a number of herbal medicines have been used in ameliorating this
problem of hepatotoxicity such as fresh garlic; (moller et al, 2009), methanolic extract of Acalypha wilkesiana; (khashab et
al, 2007).Toxic doses of paracetamol cause a serious potentially fatal
hepatotoxicity.
1.1.1 MEDICAL USES OF PARACETAMOL
In
medicine paracetamol is used to;
a) Reduce Fever:
Paracetamol is approved for reducing
fever in people of all ages. The World Health Organization (WHO) recommends
that paracetamol only be used to treat fever in children if their temperature
is greater than 38.5 °C (101.3 °F). The efficacy of paracetamol by itself
in children with fevers has been questioned and a meta-analysis showed that it
is less effective than ibuprofen. Paracetamol has a well-established role in
pediatric medicine as an effective analgesic and antipyretic.
b) Reduce Pain:
Paracetamol is used for the relief of pains
associated with many parts of the body. It has analgesic properties comparable
to those of aspirin, while its anti-inflammatory effects are weaker. It is
better tolerated than aspirin in patients in whom excessive gastric acid
secretion or prolongation of bleeding time may be a concern. Available without
a prescription, it has in recent years increasingly become a common household
drug.
1.2.2 PARACETAMOL INDUCED
HEPATOXICITY
The toxic effect of paracetamol on the liver
occur when the liver enzymes catalyzing the normal conjugation reactions are
saturated, causing the drug to be metabolized by the mixed function oxidases.
The resulting toxic metabolized, N-acetyl-p- benzoquinoneimine (NAPQI), is
inactivated by conjugation with glutathione, but when glutathione is depleted
the toxic intermediate accumulates and reacts with nucleophilic constituents in
the cell. This causes necrosis in the liver and also in the kidney tubules.
1.2.3
MECHANISM OF ACTION OF PARACETAMOL ON
HEPATOXICITY
Metabolic activation of acetaminophen
toxicity is metabolically activated by cytochrome P450 to
form a reactive metabolite that covalently binds to protein (Mitchell et al,).
The reactive metabolite was found to be N-acetyl-p-benzoquinone imine
(NAPQI), which is formed by a diret to-electron oxidation (Dahlin et al, 1984). More recently, the cytochromes 2E1, 1A2, 3A4,
and 2A6 have been reported to oxidize acetaminophen to the reactive metabolite.
Also, Dr. Gillette's laboratory showed that NAPQI is detoxified by glutathione
(GSH) to form an acetaminophen-GSH conjugate. After a toxic dose of
acetaminophen, total hepatic GSH is depleted by as much as 90%, and as a
result, the metabolite covalently binds to cytokine groups on protein, forming
acetaminophen-protein adducts (Mitchell et
al, 1973). This mechanism is shown in Fig. 2.
Fig 2:
showing the schematic representation depicting the role of Metabolism in
acetaminophen toxicity (Mitchell et al, 1973).
Events
that produce hepatocellular death following the formation of acetaminophen
protein adducts are poorly understood. One possible mechanism of cell death is
that covalent binding to critical cellular proteins results in subsequent loss
of activity or function and eventual cell death and lysis. Primary cellular
targets have been postulated to be mitochondrial proteins, with resulting loss
of energy production, as well as proteins involved in cellular ion control (Nelson,
1990).
1.3 WEIGHT
1.3.1 WEIGHT DETERMINATION
Prior
to this research the weight of these wistar rats were determined using
i)
A beam balance: this instrument
was used to measure the body weight of the rats
ii)
An electronic weigh balance: this
instrument was used to measure the organ weight of the rats
1.3.2 WEIGHT ASSOCIATED DISEASES
Excess
body weight is a very serious problem, especially in North America and Europe.
It has been referred to as a "pandemic" since it has progressively
increased over the past several decades. Moreover, excess body weight
significantly increases the risk of numerous diseases and clinical disorders,
including all-cause mortality, coronary and cerebrovascular diseases, various
cancers, type 2 diabetes mellitus, hypertension, liver disease and asthma, as
well as psychopathology, among others. Unfortunately, overweight and obesity
are now common in both young children and adolescents. Although the causes of
excess body weight are multi-factorial, the most important factors are excess
caloric intake coupled with limited energy expenditure. Therefore, lifestyle
modification can significantly reduce the risk of morbidity and mortality and
thereby increase longevity and improve the quality of life.
1.4 ORGAN WEIGHT OF RATS
1.4.1 THE LIVER
The
liver is a vital organ present in vertebrates and some other animals. It has a
wide range of functions, including detoxification, protein synthesis, and production
of biochemicals necessary for digestion. The liver is necessary for survival;
there is currently no way to compensate for the absence of liver function in
the long term, although new liver dialysis techniques can be used in the short
term.
This
organ plays a major role in metabolism and has a number of functions in the
body, including glycogen storage, decomposition of red blood cells, plasma
protein synthesis, hormone production, and detoxification. It lies below the
diaphragm in the abdominal-pelvic region of the abdomen. It produces bile, an
alkaline compound which aids in digestion via the emulsification of lipids. The
liver's highly specialized tissues regulate a wide variety of high-volume
biochemical reactions, including the synthesis and breakdown of small and
complex molecules, many of which are necessary for normal vital functions.
The
liver is a reddish brown organ with four lobes of unequal size and shape. A
human liver normally weighs 1.44–1.66 kg (3.2–3.7 lb), and is a soft,
pinkish-brown, triangular organ. It is both the largest internal organ (the
skin being the largest organ overall) and the largest gland in the human body.
It is located in the right upper quadrant of the abdominal cavity, resting just
below the diaphragm. The liver lies to the right of the stomach and overlies
the gallbladder. It is connected to two large blood vessels, one called the
hepatic artery and one called the portal vein. The hepatic artery carries blood
from the aorta, whereas the portal vein carries blood containing digested
nutrients from the entire gastrointestinal tract and also from the spleen and
pancreas. These blood vessels subdivide into capillaries, which then lead to a
lobule. Each lobule is made up of millions of hepatic cells which are the basic
metabolic cells. Lobules are the functional units of the liver.
Two
major types of cells populate the liver lobes: karat parenchymal and
non-parenchymal cells. 80% of the liver volume is occupied by parenchymal cells
commonly referred to as hepatocytes. Non-parenchymal cells constitute 40% of
the total number of liver cells but only 6.5% of its volume. Sinusoidal
endothelial cells, Kupffer cells and hepatic stellate cells are some of the
non-parenchymal cells that line the hepatic sinusoid. The liver
is also prone to many diseases. The most common include infections such as
hepatitis A, B, C, D, E, alcohol damage, fatty liver, cirrhosis, cancer, drug
damage (particularly by acetaminophen (paracetamol) and cancer drugs). Many
diseases of the liver are accompanied by jaundice caused by increased levels of
bilirubin in the system. The bilirubin results from the breakup of the
hemoglobin of dead red blood cells; normally, the liver removes bilirubin from
the blood and excretes it through bile. There are also many pediatric liver
diseases including biliary atresia, alpha-1 antitrypsin deficiency, alagille
syndrome, progressive familial intrahepatic cholestasis, and Langerhans cell
histiocytosis, to name but a few. Diseases that interfere with liver function
will lead to derangement of these processes. However, the liver has a great
capacity to regenerate and has a large reserve capacity. In most cases, the
liver only produces symptoms after extensive damage.
Liver
diseases may be diagnosed by liver function tests, for example, by production
of acute phase proteins.
1.4.2 THE KIDNEY
The
kidneys are organs that serve several essential regulatory roles in most
animals, including vertebrates and some invertebrates. They are essential in
the urinary system and also serve homeostatic functions such as the regulation
of electrolytes, maintenance of acid–base balance, and regulation of blood
pressure (via maintaining salt and water balance). They serve the body as a
natural filter of the blood, and remove wastes which are diverted to the
urinary bladder. In producing urine, the kidneys excrete wastes such as urea
and ammonium, and they are also responsible for the reabsorption of water,
glucose, and amino acids. The kidneys also produce hormones including
calcitriol, erythropoietin, and the enzyme renin.
1.4.3 THE HEART
The
heart is a hollow muscle that pumps blood throughout the blood vessels by
repeated, rhythmic contractions. It is found in all animals with a circulatory
system (including all vertebrates). The
vertebrate heart is principally composed of cardiac muscle and connective tissue.
Cardiac muscle is an involuntary striated muscle tissue found only in this
organ and responsible for the ability of the heart to pump blood. The average
human heart, beating at 72 beats per minute, will beat approximately 2.5
billion times during an average 66 year lifespan. It weighs approximately 250
to 300 grams (9 to 11 oz) in females and 300 to 350 grams (11 to 12 oz) in
males.
1.4.4 THE BRAIN
The
brain is the centre of the nervous system in all vertebrate and most
invertebrate animals—only a few invertebrates such as sponges, jellyfish, adult
sea squirts and starfish do not have one, even if diffuse neural tissue is
present. It is located in the head, usually close to the primary sensory organs
for such senses as vision, hearing, balance, taste, and smell. The brain of a
vertebrate is the most complex organ of its body. In a typical human the
cerebral cortex (the largest part) is estimated to contain 15–33 billion
neurons, each connected by synapses to several thousand other neurons. These
neurons communicate with one another by means of long protoplasmic fibres
called axons, which carry trains of signal pulses called action potentials to
distant parts of the brain or body targeting specific recipient cells.
1.4.5 THE TESTES
The
testicle (from Latin testiculus, diminutive of testis, meaning
"witness" of virility,plural testes) is the male gonad in animals.
Like the ovaries to which they are homologous, testes are components of both
the reproductive system and the endocrine system. The primary functions of the
testes are to produce sperm (spermatogenesis) and to produce androgens,
primarily testosterone. Both functions of the testicle are influenced by
gonadotropic hormones produced by the anterior pituitary.
1.4.6 THE LUNGS
The
lung is the essential respiration organ in many air-breathing animals,
including most tetrapods, a few fish and a few snails. In mammals and the more
complex life forms, the two lungs are located near the backbone on either side
of the heart. Their principal function is to transport oxygen from the
atmosphere into the bloodstream, and to release carbon dioxide from the
bloodstream into the atmosphere. This exchange of gases is accomplished in the
mosaic of specialized cells that form millions of tiny, exceptionally
thin-walled air sacs called alveoli.
1.5 OBJECTIVE
OF STUDY
The
objective of this study is to determine the effect of methanolic leaf extract
of Acalypha wilkesiana in paracetamol
induced hepatoxicity on the weight parameters of Wistar rats
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