الفهرس 
IntroductionOnly 14 pages are availabe for public view
Abstract
Summary Paracetamol (APAP), an over-the-counter drug, is a commonly used antipyretic and analgesic which can lead to liver
damage if taken in overdose. APAP is generally safe for use at
recommended doses of 1 g per single dose and up to 4 g per day
for adults. It is also safe for children and infants at recommended
doses. Excessive use of APAP can damage the liver and if not
treated, an overdose can lead to liver failure and death. In
therapeutic dose, APAP is converted by drug metabolizing
enzymes to water-soluble metabolites and secreted in the urine.
Saturated and excess APAP is oxidatively metabolized by hepatic
cytochrome p450 system to a toxic metabolite, namely, N-acetylpbenzoquinone imine (NAPQI). The NAPQI is normally
detoxified by a nonprotein thiol known as GSH with both oxidant
scavenger and redox-regulation capacities. GSH is a major
antioxidant system and a crucial component of host defense
which is responsible for scavenging reactive free radicals
produced through the metabolism process within the liver to
prevent cell injury. The toxic dose of APAP caused the depletion
of GSH resulting in accumulation of NAPQI which then
covalently binds to the cysteinyl sulfhydryl groups of cellular
proteins forming NAPQI-protein adducts. This event results in the
generation of ROS including the hydrogen peroxide, superoxide
anion (O
2−
), and hydroxyl (OH
−
) radical that affect the cellular
membrane and induce lipid peroxidation and also cause cellular
necrosis.
Apricot (Prunus armeniaca L.) is one of the most
important commercial crops and worldwide preferable in the
markets of production and consumption. Apricot is mostly
suitable for manufacturing in many commercial forms such as
fresh fruit, dried fruit and fruit juice. Apricot is considered as a
good source of dietary antioxidant, with its content of flavonoids
and carotenoids. Flavonoids are a large group of polyphenolic
Summary
17 9
antioxidants that exhibit a wide range of biological activities
including the inhibition of lipid peroxidation , capillary
permeability and platelet aggregation. They also inhibit the
enzymes responsible for superoxide anion production (xanthine
oxidase and protein kinase C) and ROS generation
(cyclooxygenase, lipoxygenase and NADH oxidase). Apricot
kernel is an important source of dietary protein as well as oil an d
fiber. It is well known that apricot kernels contain a wide variety
of bioactive components, and that consumption of apricot kernel
has been associated with a reduced risk of chronic diseases.
Interestingly, apricot kernels contain as much as 50% oil. Apricot
kernel oil (AO) is rich in mono- and polyunsaturated fatty acids,
with oleic and linoleic acids being the major constituents, and a
number of minor components, such as tocopherols and phenolic
compounds. Monounsaturated and polyunsaturated fatty acids, as
well as minor lipid components, play an important role in human
nutrition and health. Several studies indicated that apricot and its
kernel exhibited antioxidant protection, hypolipidemic, and
anti-inflammatory properties. Apricot and its kernel may have
hepatoprotective effects and prevent cellular damage by inhibiting
lipid peroxidation, improving antioxidant enzymes and preventing
DNA damage.
This study was designed to investigate the protective effect
of fresh, dried apricots and its kernel added to diet (10% and 20%
w/w) on paracetamol-induced cellular toxicity in rats comparing
that with healthy control rats.
Eighty adult male albino rats Spargue Dawly strain
weighing 115+ 5g were fed with standard balanced diet and water
ad libitum for a one week acclimitation period , then the eighty
rats were divided into eight groups (10 per each) as follow:
Group 1: rats fed with normal balanced diet for 6 weeks
followed by a single dose, i.p injection, of saline (-ve
control).
Summary
18 0
Group 2: rats fed with normal balanced diet for 6 weeks
followed by a single dose, i.p injection, of APAP (500
mg\kg body weight (+ve control).
Group 3: rats fed with 10% fresh apricot containing diet for 6
weeks followed by a single dose, i.p injection, of
APAP (500 mg/kg body weight).
Group 4: rats fed with 20% fresh apricot containing diet for 6
weeks followed by a single dose, i.p injection, of
APAP (500 mg/kg body weight).
Group 5: rats fed with 10% dried apricot containing diet for 6
weeks followed by a single dose, i.p injection, of
APAP (500 mg/kg body weight).
Group 6: rats fed with 20% dried apricot containing diet for 6
weeks followed by a single dose, i.p injection, of
APAP (500 mg/kg body weight).
Group 7: rats fed with 10% apricot kernel conta ining diet for 6
weeks followed by a single dose, i.p injection, of
APAP (500 mg/kg body weight).
Group 8: rats fed with 20% apricot kernel containing diet for 6
weeks followed by a single dose, i.p injection, of
APAP (500 mg/kg body weight).
Food intake was recorded daily. The animals were weighed
weekly to monitor the body weight changes and FER. After 24
hours of APAP injection and 12 hour fasting, the animals were
scarified under ether anesthesia and blood samples were collected
directly from portal vein. The organs (liver, kidney, and testis)
were separated immediately, and then weighed, part of liver,
kidney, and testis specimens were preserved in 10% formalin for
microscopic examination.
Summary
18 1
At the end of experiment the following nutritional, biological
and biochemical parameters were measured:
Apricot (fresh and dried) and apricot kernel were
chemically analyzed for their content of moisture, proteins,
carbohydrates, fibers, fats, ash, ascorbic acid, total
carotenoids, and total phenolics.
Food intake, body weight gain, and feed efficiency ratio.
Relative weight of liver, kidney, and testis.
Serum total protein and albumin levels.
Serum bilirubin (total, direct, and indirect) levels.
Serum liver enzymes activities (AST, ALT and ALP).
Serum urea, creatinine and uric acid levels.
Serum acid phosphatase (total, prostatic and non prostatic)
activity.
Serum lipid profile (TC, TAG, HDL-C, LDL-C, VLDL-C)
levels.
Liver, kidney and testis GSH level.
Liver, kidney and testis MDA level.
Also, microscopic examination of liver, kidney and testis
was performed.
The results of our study can be summarized as follow:
(1)Nutrients composition of fresh apricot, dried
apricot, and apricot kernel:
Values revealed that each 100g of fresh apricot contains
86.10+ 3.5 g moisture, 0.84+ 0.3g protein, 0.04+ 0.02g fat,
12.19+ 6.5g total CHO, 2.30+ 0.3 g total fiber, and 0.84+ 0.4g
ash. Also, each 100 g of dried apricot contains 28.26+ 7.0 g
moisture, 1.88+ 0.5g protein, 0.08+ 0.02 g fat, 64.61+ 2.5 g total
CHO, 7.53+ 1.5 g total fiber, and 5.17+ 3.8 g ash.Moreover,
analysis of apricot kernel proved that each 100 g contains 4.88 +
2.3 g moisture, 25.65+ 3.6 g protein, 34.60+ 2.7 g fat, 32.29+ 1.9
g total CHO, 24.72+ 10 g total fiber, and 2.58+ 1.8 g ash.
Summary
18 2
In addition, the results of this study revealed that ascorbic
acid concentration was 35.11+1.1, 15.07+ 1.07, and 2.6+
0.62mg/100g for fresh apricot, dried apricot and apricot kernel
respectively. While, total carotenoid content was 4.11+0.13,
6.69+0.22, and 1.45+0.14mg/100g fresh apricot, dried apricot and
apricot kernel respectively.Also, our data represents that total
phenolic content concentration in fresh apricot, dried apricot, and
apricot kernel was55.38+0.10, 80.0+0.11, and 2.8+0.18mg as
GAE/100g respectively.
(2) Food intake, body weight gain, feed efficiency ratio and
relative organs weight:
Paracetamol administration didn’t cause change in daily
food intake, body weight gain, and relative organs weight.
Moreover, supplementation with fresh and dried apricot
(10&20%) before APAP administration caused significant
increase in food intake and body weight gain. On the other hand ,
supplementation with apricot kernel (10&20%) caused significant
decrease in food intake and body weight gain. Also, there was no
significant change in FER between healthy control and APAP
control rats. In addition, there was no significant change in
relative organs weight between all groups.
(3) Liver function measurements:
Our data represents a marked decrease in serum total
protein and albumin in APAP-control group. In contrast,
paracetamol caused marked elevation in serum total, direct, and
indirect bilirubin levels, also, AST, ALT, and ALP activities
which indicate liver dysfunction.
Apricot and its kernel demonstrated a hepatoprotective
effect as their supplementation maintains the liver function
parameters. This could be attributed to their hepatocytes cell
membrane stabilization, which then prevents the cystolic released
in circulation. Also, their antioxidant effect and their ability to
replenish GSH level that can help in the defense against any liver
Summary
18 3
damage. The improvement in liver parameters was dose
dependent.
(4) Kidney function measurements:
Paracetamol control group showed renal dysfunction that
was manifested by marked elevation of serum urea, creatinine and
uric acid levels.
Our results proved the protective effect of apricot and its
kernel on kidney functions as clear by the reduction of serum
urea, creatinine, and uric acid levels. The data proved that the
protective effect of fresh and dried apricot was dose dependent.
Their nephro-protective effect may be due to their highly content
of bioactive compounds mainly carotenes, flavonoids, and
ascorbic acid. These compounds are able to scavenge ROS , thus
preventing oxidative tissue damage.
(5) Testis function measurements:
It was noticed that there was significant elevation in serum
total, non-prostatic, and prostatic ACP activity in APAP-control
rats indicating testicular damage.
Moreover, supplementation of rat’s diets with apricot and
its kernel showed testicular protection as manifested by marked
reduction in serum total, non-prostatic, and prostatic ACP
activity. This protection may be due to their content of vitamin C
that is an important antioxidant which protects spermatogenesis
from free radical damage. Also, Carotenoids are probably
nonfocal antioxidants that indirectly affect the male fertility.
Mixtures of carotenoids or associations with others antioxidants
(e.g. vitamin C and vitamin E) can increase their ability to protect
against lipid peroxidation induced by APAP.
Summary
18 4
(6)Lipids profile measurements:
APAP-control rats showed disturbance in serum lipids
profile which detected by the elevation of serum TC, TAG, LDLC, and VLDL-C levels and reduction of HDL-C level. Our
present study proved the hypocholesterolemic and hypotriglyceredemic effect of apricot and its kernel , as their
administration cause a marked dose-dependent decrease in serum
TC, TAG, LDL-C and VLDL-C levels, and noticeable elevation
of HDL-C level. The hypolipidemic effect of fresh, dried apricots
and apricot kernel was dose dependent.
(7) Antioxidant status and lipid peroxidation measurments:
Our study indicated a disturbance in antioxidant status
including liver, kidney, and testis GSH that can be inferred by the
reduction of its level in APAP-control rats. Also, there was an
increase in lipid peroxidation that can be reflected by increasi ng
liver, kidney, and testis MDA level (a lipid peroxidation marker).
Administration of apricot and its kernel maintain the
antioxidant status and lipid peroxidation that were manifested by
the marked increase in tissue GSH and a marked decrease in
tissue MDA levels. These compounds have antioxidant capacity
to scavenge ROS and spare α-tochopherol.
(8) Microscopic examination of liver, kidney, and testis
samples:
Liver section from APAP- control rats showed congestion of
fatty degeneration of hepatocytes, Kupffer cells activation and
vaculation of hepatocytes. Also, kidney section from APAPcontrol rats showed hypertrophy and vaculation of glomerular tuft
and eosinophilic protein cast in the lumen of renal tubules. While,
testis from APAP-control rats is characterized by degeneration of
spermatogoneal cells lining of seminiferous tubules.
Summary
18 5
Co-administration of fresh apricot, dried apricot, and apricot
kernel normalized tissue lipid peroxidation level and prevented
the reduced tissue GSH level. Even they possess significant
quantity of polyphenols like flavonoids. In fact, these principles
play a major role in free radical scavenging activity and further
these may contribute to cellular protection. The protective
property of them is further confirmed by significant improvement
of the liver, kidney and testis architecture by reversing the cellular
congestion, inflammatory cells, cellular necrosis and apoptosis.
Apricot addition to diet ameliorated these alterations mainly by
radical scavenging activity.Antioxidants in apricot may prevent
APAP-induced cellular damage. The flavonoids , carotenoids,
vitamin A, and vitamin C in apricots are all antioxidants in
isolation; flavonoids and vitamin A stabilize cell membranes by
inhibiting the lipid peroxidation process, whereas carotenoids and
vitamin C act as nonfocal antioxidants. The association of
carotenoids with other antioxidants augments the overall
protective effect on lipid peroxidation that causes cellular
damage.