Abstract
Objective
The aim of the present study was to evaluate the protective role of pumpkin oil on
experimental alcohol – induced hepatotoxicity.
Materials and methods
Rats are divided into three groups of 10 animals each. Group one (G1) was the
control group is orally given distilled water for 4 weeks. Group two (G2) is given
absolute ethyl alcohol (10%) in drinking water for 4 weeks. Group three (G3)
alcohol– administered rats were pretreated with pumpkin oil (50 mg/kg body weight)
three times per week for three weeks and alcohol (10%) three times per week (at the
first two weeks of the experiment).
Results
Alcohol caused a marked rise in serum alanine aminotransferase (ALT), aspartate
aminotransferase (AST), alkaline phosphatase (ALP) and gamma glutamyl
transferase (γGT) activities. Concerning oxidative stress and antioxidant defense
system, the depleted hepatic glutathione content, glutathione-S-transferase and
catalase activities of alcohol-administered rats were potentially increased above
normal levels as a result of pretreatment with pumpkin oil. However, while elevated
lipid peroxidation was noticed in alcohol treated rats, pretreatment with pumpkin oil
produced a detectable decrease in lipid peroxidation level.
Conclusion
The natural plant components found in pumpkin could improve the liver against
alcohol-induced liver toxicity and oxidative stress. However, further clinical studies
are required to assess the safety and benefits of pumpkin oil in human beings.
Keywords



Pumpkin oil-hepatotoxicity;
Rattus norvegicus;
Oxidative stress
1. Introduction
Alcohol is the most psychoactive substance used after caffeine. Chronic alcoholism
is a major public health problem and causes disease and toxicity. Accumulating
evidence suggest that intermediates of oxygen reduction may be associated with the
development of alcoholic disease (Calabrese et al., 2002). Ethanol or its metabolites
can prompt a sharp increase of free radicals in the human body (e.g. hepatic cells)
by acting as a prooxidant or by reducing antioxidant levels and contributing to the
progression of a variety of chronic diseases (Clemens and Jerrells, 2004). Reactive
oxygen species (ROS) are highly reactive and can damage lipids, proteins and DNA
(Arteel, 2003). The ROS, the main culprit, the other one being reactive nitrile species
(RNS) are capable of damaging several cellular components such as proteins, lipids
and DNA (Koneru et al., 2011).
Liver is the primary organ for the metabolism of ingested alcohol (Shanmugam et al.,
2010).The liver is the largest, important organ and the site for essential biochemical
reactions in the human body. It has the function to detoxify toxic substances and
synthesize useful biomolecules. Therefore, damage to the liver leads to grave
consequences. Alcohol induces oxidative stress which is known to cause liver injury
that is many biochemical metabolic reactions occur as a result of it. Some of these
include redox state changes, production of reactive acetaldehyde, damage to the
mitochondria of cells, cell membrane damages, hypoxia, effects on immune system,
altered cytokine production, and induction of CYP2E1 and mobilization of iron
(Baskaran et al., 2010). Alcoholic liver disease is a worldwide health problem which
has three manifestations in form of fatty liver/steatosis, alcoholic hepatitis and liver
cirrhosis. At least 80% of chronic alcoholic consumers may develop steatosis, 10–
35% alcoholic hepatitis and approximately 10% liver cirrhosis. Intake of alcohol
causes accumulation of reactive oxygen species (ROS) like superoxide, hydroxyl
radical and hydrogen peroxide in the hepatic cells that oxidize the glutathione which
leads to lipid peroxidation of cellular membranes, oxidation of protein and DNA
resulting in hepatic damage (Muhammad et al., 2009). Initially, in the liver alcohol is
metabolized into the highly toxic acetaldehyde by the enzyme alcohol
dehydrogenase. Acetaldehyde is then oxidized to acetate by acetaldehyde oxidase
or xanthine oxidase giving rise to ROS via cytochrome P450 2E1. Prolonged
consumption of alcohol increases nitric oxide (NO) level which leads to formation of
toxic oxidant peroxynitrite. Low capacity of antioxidants in this situation leads to
damage of the cells of the hepatic cells and the cell organelles with the release of
reactive aldehydes and ROS (Saalu et al., 2012). Treatment options available for
common liver diseases such as cirrhosis, fatty liver and chronic hepatitis are
inadequate in modern medicine. Conventional drugs used in the treatment of liver
diseases such as corticosteroids, antiviral, immunosuppressant may lead to serious
adverse effects; they may even cause hepatic damage on prolonged use. Therefore,
alternative drugs in the form of herbal medicines which are now used for the
treatment of liver diseases are sought instead of currently used drugs of doubtful
efficacy and safety (Vetriselvan et al., 2010).
Natural antioxidants are found in many compounds classified as secondary plant
metabolites, e.g. in polyphenols (phenolic acids, flavonoids) and terpenoids
(carotenoids), and the consumption of foods which contain these compounds in large
quantities seems to play an important role in prophylaxis against many diseases.
Epidemiological studies have revealed that the incidence of some cardio-vascular
and cancer diseases is less frequent when fruit and vegetables are consumed
regularly (Horubała, 1999), which should be attributed to the large quantities of the
phenolics present. Phenolic compounds belong to a numerous group of antioxidants
and act via different modes, e.g. by ‘scavenging’ free radicals. Phenolic compounds
can also enhance the activity of other antioxidants, for example that of fat-soluble
vitamins (Dru_zyń ska et al., 2008).
Pumpkin seeds (Cucurbita pepo L.) are a rich source of unsaturated fatty acids,
antioxidants and fibers, known to have anti-atherogenic and hepatoprotective
activities (Makni et al., 2008). Pumpkin is one such plant that has been frequently
used as functional food or medicine (Caili et al., 2006). Some of its common uses in
most countries are for diabetes where it is used internally, as well as externally for
management of worms and parasites. Treatment of spontaneously hypertensive rats
with felodipine or captopril monotherapy or combined with pumpkin seed oil
produced improvement in the measured free radical scavengers in the heart and
kidney (Al-Zuhair et al., 2000).
Being rich in unsaturated fatty acids especially linoleic and oleic acid and
tocopherols and with very high oxidative stability, pumpkin seed oil is suggested to
be a healthy addition towards human diet and have potential suitability for food and
industrial applications (Stevenson et al., 2007). In addition to the carotenoids and
gamma aminobutyric acids (GABA) found in the fruits (Liu, 2001), there are other
biologically active ingredients, which are found in pumpkins (Gossell-Williams et al.,
2008) such as, sterols, proteins and peptides, polysaccharides, para-aminobenzoic
acid and fixed oils. Essential fatty acids are necessary for human health but the body
cannot make them; so they must be taken through food (Eynard et al., 1992).
Pumpkin seed oil's main nutrients are: essential fatty acid-omega 6, omega 9,
phytosterols, and antioxidants such as carotenoids, vitamin A and vitamin E
(Murkovic et al., 1996). Linoleic acid, a polyunsaturated fatty acid present in pumpkin
seed oil, is known to increase membrane fluidity and allows for osmosis, intracellular
and extra cellular gaseous exchange (Lovejoy, 2002). Pumpkin seed oil includes
fatty acids: palmitic (C 16:0), stearic (C 18:0), oleic (C 18:1) and linoleic (C 18:2)
(Kulaitiene et al., 2007). Antioxidants are the substances that when present in low
concentration significantly delay or reduce the oxidation of the substrate (Halliwell,
2000).
Compared pumpkin oil with another oil, Jia et al. (2011) evaluated the protective
effects of almond oil against acute hepatic injury induced by carbon tetrachloride in
rats. These result demonstrated that almond oil has potent hepatoprotective effects,
and could be developed as a functional food for the therapy and prevention of liver
damage. It is well known that almonds contain a wide variety of phenolic acids and
flavonoids and the consumption of almonds has been associated with a reduced risk
of chronic diseases. (Milbury et al., 2006). The almond contains as much as 50% oil
(Zhang et al., 2009). As one of the most popular vegetable oils, almond oil is rich in
mono and poly-unsaturated fatty acids, with oleic and linoleic acids as the major
constituents, and a number of minor components such as tocopherols and phenolic
compounds. Monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA), as
well as minor lipid components, play an important role in human nutrition health
(Turan et al., 2007). Diets rich in these compounds can decrease blood pressure and
total blood cholesterol levels, prevent oxidative stress and maintain body weight in
humans. Some studies have shown the antioxidant activity and free radical
scavenging capacity of almond oil in vitro. The antioxidant activities of minor
components of almond oil have also been reported. (Espín et al., 2000, Li et al.,
2007 and Ramadan and Moersel, 2006).
Based on these previous studies, the present work aimed to assess the protective
and antioxidant effects of pumpkin oil against alcohol induced hepatotoxicity and
oxidative stress in albino rats.
2. Materials and methods
2.1. Experimental animals
Adult male albino rats (Rattus norvegicus) weighing 120–150 g were used in the
present study. The animals were obtained from the animal house in the
Ophthalmology Research Center, Giza, Egypt. They were kept under observation for
two weeks before the onset of the experiment to exclude any intercurrent infection.
The animals were kept at room temperature and exposed to natural daily light–dark
cycles. Rats were fed ad libitum and clean water was continuously available. All
animal procedures are in accordance with the recommendations for the proper care
and use of laboratory animals stated by the Canadian Council on Animal Care
(CCAC, 1993).
2.2. Chemicals
Pumpkin oil was purchased from El Captin pharmaceutical company. All other
chemicals used for the investigation were of analytical grade.
2.3. Doses and treatment
Alcoholism was experimentally induced in animals by giving absolute ethyl alcohol
(10%) in drinking water for 15 days before the experiment (Hekmatpanah et al.,
1994). Pumpkin oil dose was adjusted to 50 mg/kg and were given daily for 4 weeks
(Al-Zuhair et al., 2000).
2.4. Experimental design
Animals were divided into three groups comprising ten animals each:
1
Group 1 (normal control) is orally given the equivalent volume of the vehicle 1
(distilled water) daily for 4 weeks.
2
Group 2 (positive”+ve”control) is given absolute ethyl alcohol (10%) in drinking
water for 4 weeks (Hekmatpanah et al., 1994).
3.
Group 3 (treated with pumpkin oil and alcohol) is given absolute ethyl alcohol
(10%) in drinking water for 15 days before the experiment (Hekmatpanah
et al., 1994). Pumpkin oil dose was adjusted to 50 mg/kg and were given daily
for 4 weeks (Al-Zuhair et al., 2000).
2.5. Blood and organ sampling
Rats were anesthetized with diethyl ether and after decapitation and dissection,
blood samples were collected and liver was excised for physiological and
biochemical assays as well as for histopathological studies. Blood sample was
collected from jugular vein of each animal (5 ml) in a centrifuge tube and left to clot
at room temperature for 45 min. Sera were separated by centrifugation at
3000 r.p.m. at 30 °C for 15 min and kept frozen at −30 °C for various physiological
and biochemical analyses.
Liver from each animal was excised after dissection. One part was fixed in buffered
formalin for 24 h, trimmed and then transferred into 70% alcohol for histopathological
examination. 0.5 g was homogenized in 5 ml 0.9% NaCl (10% w/v) using teflon
homogenizer (Glas-Col, Terre Haute, USA).
2.6. Biochemical analyses
Serum total bilirubin concentration was determined by a colorimetric procedure using
kits obtained from Biodiagnostic (Egypt) according to Walter and Gerad (1970).
Serum ALT and AST activities were determined by using kits obtained from
Biodiagnostic (Egypt) according to the methods of Reitman and Frankel (1957).
Serum ALP and GGT were determined by using kits obtained from Biodiagnostics
according to the method ofBelfield and Goldberg (1971) and Szasz (1969),
respectively. Serum total protein was determined by using kits obtained from
Biodiagnostics according to the method of Young (2001). Serum LDH was estimated
according to the method described by Bühl and Jackson (1978), using reagent kit
purchased from Stanbio Laboratories (Texas, USA). Liver glutathione (GSH) was
determined according to the method of Beulter et al. (1963). Liver lipid peroxidation
was determined by measuring thiobarbituric acid reactive substances (TBARS)
according to the method of Preuss et al. (1998). Liver glutathione-s-transferase
activity was assayed using the method of Matkovics et al. (1998) andMannervik and
Gutenberg (1981). Liver catalase activity were assayed following the method of Kar
and Mishra (1976).
2.7. Histopathological studies
Fixed liver tissue samples were embedded after dehydration in paraffin wax,
sectioned at thickness of 5 μm and stained with hematoxylin and Eosin (HandE) for
general histopathological examination using the light microscope.
2.8. Statistical analysis
The data were analyzed using the one-way analysis of variance (ANOVA) (PCSTAT, 1985) followed by LSD analysis to compare various groups with each other.
Results were expressed as mean ± standard error (SE). F-probability, obtained from
one-way ANOVA, expresses the effect between groups.
3. Results and discussion
One-way ANOVA revealed that the effect on the variables of oxidative stress and
antioxidant system was of p < 0.001 between groups.
Changes in different serum variables related to liver function are presented in Table
1 and Table 2. Concerning serum enzymes related to liver function, the alcoholadministered rats exhibited significant increase (p < 0.01; LSD) in ALT, AST and ALP
activities. The pre-treatment with pumpkin oil successfully ameliorated the elevated
activities of ALT and ALP, although recorded non-significant changes on AST and γ
GT activities. Serum total bilirubin concentration was elevated in alcoholadministered rats but recording a significant decrease in pumpkin oil pretreated rats.
Serum total protein level was increased as a result of administration of alcohol alone,
while it was significantly decreased in animals pretreated with pumpkin oil. Serum
LDH activity was significantly increased in alcohol administered rats, although have a
non-significant increase in pumpkin oil pretreatment.
Table 1.
Protective effect of pumpkin oil on serum liver function activities in alcohol treated rats.
Parameters
Treatme
nts
G1
Normal
G2
(Alcohol)
G3
Pumpkin
oil + Alc
ohol
FProbabili
ty
LDS at
5% level
LDS at
1% level
ALT
(U/ml)
39.00 ± 0.
815d
56.50 ± 0.
289a
47.00 ± 0.
575c
%
chan
ge
–
%
chan
ge
–
ALP
(IU/L)
429.5 ± 6
.75b
781.5 ± 6
.95a
386.0 ± 4
.62b
%
chan
ge
–
γ – GT
(U/L)
9.28 ± 0.
746a
12.15 ± 5
.79a
2.23 ± 0.
281a
%
chan
ge
–
44.8
7
−16.
81
AST (U/ml)
185.00 ± 0.
001b
202.00 ± 0.
575a
201.50 ± 0.
289a
P < 0.000
1
–
P < 0.0001
–
P < 0.00
01
–
P < 0.07
71
–
2.88
–
9.84
–
16.06
–
–
–
4.04
–
13.79
–
22.51
–
–
–
9.19
−0.7
41
81.9
6
−50.
61
30.9
3
−81.
65
Data are expressed as mean ± standard error.
Number of animals in each group is ten.
Mean, which have the same superscript symbol(s), are not significantly different.
Percentage changes (%) were calculated by comparing normal group with alcohol treated
group and pre-treated alcohol group with alcohol treated group.
Table options
Table 2.
Protective effect of pumpkin oil on serum total bilirubin, total protein levels and lactate
dehydrogenase activity in alcohol treated rats.
Parameters
Treatments
G1
Normal
G2
(Alcohol)
Total
bilirubin
(mg/dl)
2.50 ± 0.289
%
chang
e
–
ab
3.55 ± 0.685
a
42.0
Total
protein
(g/dl)
6.80 ± 0.34
9a
7.20 ± 0.42
3a
%
chang
e
–
5.88
LDH (U/L)
261.48 ± 18.4
6c
343.00 ± 21.0
8ab
%
chang
e
–
31.18
Parameters
Treatments
G3
Alcohol + Pumpk
in oil
F-Probability
LDS at 5% level
LDS at 1% level
Total
bilirubin
(mg/dl)
1.03 ± 0.132
c
P < 0.004
1.22
1.71
%
chang
e
−70.9
9
Total
protein
(g/dl)
6.58 ± 0.61a
%
chang
e
−8.61
LDH (U/L)
367.13 ± 8.16a
%
chang
e
7.03
–
–
–
P < 0.529
–
–
–
–
–
P < 0.0011
43.81
61.42
–
–
–
Data are expressed as mean ± standard error.
Number of animals in each group is ten.
Mean, which have the same superscript symbol(s), are not significantly different.
Percentage changes (%) were calculated by comparing normal group with alcohol treated
group and pre-treated alcohol group with alcohol treated group.
Table options
These results are in agreement with Padmanabhan and Jangle (2014) who
illustrated that alcohol feeding causes elevation in serum activities of AST, ALT,
ALP, γGT and LDH enzymes which are markers of liver damage. In the study
reported by Vidhya et al. (2009) ethanol treated group resulted in significant increase
in AST and ALT activities, which is an indication of hepatocellular damage in rats,
whereas treatment with quercetin reduced ethanol –induced toxicity as indicated by
the lowering of marker enzymes. In alcohol intoxication as a result of structural
changes, an increase in the cell membrane permeability to ions results. The increase
in membrane permeability causes leakage of ALT and AST into blood circulation as
shown by abnormally high levels of serum hepatic markers. The observations
by Vermaulen et al. (1992) which indicated that ALT, AST, γGT and ALP are
normally located in the cytoplasm and released into circulation after hepatic cellular
damage. Nkosi et al. (2005) and Oboh (2005) observed that the administration of
pumpkin seeds proteins after CCl4 intoxication resulted in significantly reduced
activity levels of lactate dehydrogenase, alanine transaminase, aspartate
transaminase and alkaline phosphatase.
Table 3 show the effect of the tested pumpkin oil on the liver oxidative stress
markers and antioxidant defense system of normal and alcohol-administered rats.
The pre-treatment with pumpkin oil produced a potential increase (p < 0.01; LSD) of
the glutathione level, glutathione-S-transferase and catalase activities when
compared to alcohol treated group which exhibited significant decrease in GSH level,
glutathione-S-transferase and catalase activities as compared to normal control
group. Liver lipid peroxidation recorded a significant increase as a result of alcohol
administration while significantly decreased in pumpkin oil treated rats corresponding
to control group.
Table 3.
Protective effect of pumpkin oil on liver glutathione level, glutathione-s-transferase and
catalase activities and lipid peroxidation level in alcohol treated rats.
Parameters
Treatments
G1
Normal
G2
(Alcoholic)
G3
Alcohol + Pu
mpkin oil
F-Probability
LDS at 5%
level
LDS at 1%
level
GSH
mg/gm
73.70 ±
1.09a
54.53 ±
1.12d
68.93 ±
1.55b
%
chan
ge
–
39.5
8
54.4
9
P < 0.00
01
4.65
–
6.51
GST
U/gm
6.04 ± 0.
146b
3.63 ± 0.
154c
6.98 ± 0.
049a
%
chan
ge
–
9.77
92.2
9
–
–
P < 0.00
01
0.479
–
0.672
Catalase
U/g
1.90 ± 0.0
01a
0.371 ± 0.
001b
1.71 ± 0.1
62a
%
chan
ge
–
80.4
7
360.
92
–
–
P < 0.000
1
0.256
–
0.359
MDA
nmol/g
36.31 ± 0.
255b
50.97 ± 0.
921a
23.48 ± 0.
363c
%
chan
ge
–
28.7
6
35.3
3
–
–
P < 0.000
1
1.72
–
2.42
–
–
Data are expressed as mean ± standard error.
Number of animals in each group is ten.
Mean, which have the same superscript symbol(s), are not significantly different.
Percentage changes (%) were calculated by comparing normal group with alcohol treated
group and pre-treated alcohol group with alcohol treated group.
Table options
The current results are in agreement with Brown et al., 2004, Mallikarjuna et al.,
2008 and Shanmugam et al., 2011 who found that GSH acts as an antioxidant and a
powerful nucleophile, critical for cellular protection, such as detoxification of reactive
oxygen species (ROS), conjugation and excretion of toxic molecules and control of
inflammatory cytokine cascade (Brown et al., 2004). It has been mentioned that the
antioxidant activity of plants might be due to their phenolic compounds (Hatapakki
et al., 2005). The levels of GSH were significantly decreased in alcohol-treated rats,
as well as earlier published reports, which showed that the GSH concentration
decreases during alcohol ingestion (Mallikarjuna et al., 2008 and Shanmugam et al.,
2011). It is easily susceptible to lipid peroxidation. Pumpkin seed oil has shown to
possess strong antioxidant properties in experimental animals (Dreikorn et al.,
2002). Ahmed et al. (2009) reported that pumpkin seed oil administration showed a
significant elevation in the striatum and serum glutathione level at all-time intervals in
adult male albino rats. Pumpkin seeds of Cucurbita pepo L. a herbaceous plant of
Cucurbitaceae family, contain 40.4–55.6% of linoleic acid: LA; 18:2 n-6, x-6 fatty acid
(Al-Khalifa, 1996, Ganzera et al., 1999 and Jamieson, 1943). They may have
beneficial effects in health and may prevent chronic diseases (Al-Khalifa,
1996 and Kumar et al., 2006).
Catalase acts as a preventive antioxidant and plays an important role in the
protection against the deleterious effects of LPO (lipid hydroperoxide). Reports have
shown that there is a significant decrease in the activities of catalase in alcoholic
subjects (Husain and Somani, 1997). A decreased activity of CAT was due to
exhaustion of the enzyme as a result of oxidative stress induced by the alcohol.
Presumably, a decrease in CAT activity could be attributed to cross-linking and
inactivation of the enzyme protein in the lipid peroxides.
Xu (2000) who found that pumpkin polysaccharide could increase the SOD and
GSH-Px activity and reduce the MDA content in tumor mice serum (Xu,
2000). Pandanaboina et al. (2012) who observed a significant increase in lipid
peroxidation during alcohol consumption, as reported by earlier studies (Das and
Vasudevan, 2006). The alcohol intoxication increases lipid peroxide production
(LPO) in various tissues, and is indicative of tissue oxidative stress. Nearly 60–80%
ingested alcohol is metabolized in the liver, and this makes it more vulnerable than
other organs to alcohol-induced oxidative stress (Lieber, 2003). This concept is
supported by the larger extent of an increase in LPO production in the liver, as
compared to other organs. Plasma and liver contain enzymes such as catalase
(CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx), which
showed contribute to the antioxidant defense mechanism (Lee et al., 2002). Mary
et al. (2002) and Visavadiya and Narasimhacharya (2007) observed a decrease in
the activities of the antioxidant enzymes SOD, CAT and GPx in
hypercholesterolemic rats. Such decreases may be associated to the production of
a-, b-unsaturated aldehydes during lipid peroxidation. These compounds have the
ability to increase oxidative stress by promoting the cellular consumption of
glutathione and by inactivating selenium-dependent glutathione peroxidase (Kinter
and Roberts, 1996). GSH serves as a substrate for the enzyme GPx, and it had
been suggested that, through its activity, GSH protects plasma against oxidative
damage. Moreover PUFAs (linoleic acid “LA” and alpha-linolenic acid “ALA”) have
displayed protection against lipid peroxidation increasing the levels of several cellular
antioxidants such as ascorbic acid, a-tocopherol and GSH (Nagao et al., 2005).
Fig. 1 showed the histology of liver of normal control. There was no histopathological
alteration observed and the normal histological structure of the central vein and
surrounding hepatocytes.
Fig. 1.
A transverse section of a liver of normal control (distilled water) rat showing a central vein
(CV), hepatic cords (h) and sinusoids in between. ×400.
Figure options
The portal area in ethyl alcohol administered rats (G2) showed severe dilatation and
congestion in the portal vein associated with periductal fibrosis surrounding the bile
ducts (Fig. 2). Alcohol administered rats also recorded fatty change in diffuse
manner all over the hepatocytes (Fig. 3). Fig. 4 showed fatty change in diffuse
manner in the hepatocytes in pumpkin oil pretreated rats.
Fig. 2.
The portal area showed sever dilatation and congestion in the portal vein (PV) associated
with periductal fibrosis (f) surrounding the bile ducts (b) in ethyl alcohol treated group (G2).
×400.
Figure options
Fig. 3.
Fatty change was observed in diffuse manner (d) all over the hepatocytes in ethyl alcohol
treated group (G2). ×400.
Figure options
Fig. 4.
The hepatocytes showed fatty change in diffuse manner in pumpkin pretreated group (G3).
×400.
Figure options
The current study was in agreement with Padmanabhan and Jangle (2014).who
found that the higher levels of alcohol intake cause cirrhosis and liver damage by
enhancing lipid peroxidation in the liver. Acetaldehyde the toxic metabolite of alcohol
depresses liver GSH by conjugating with sulphydryl groups of GSH (Maruthaappan
and Shree, 2009). In both acute and chronic administration of alcohol causes
formation of cytokines in large amounts, particularly TNF–α by hepatic Kupffer cells,
which plays a major role in causing hepatic damage. Moreover, chronic
administration of alcohol results in accumulation of hepatic lipids, lipid peroxides
leading to the autooxidation of hepatic cells acting as pro-oxidants and decreasing
antioxidant levels thereby resulting in a noteworthy hepatotoxicity. (Kumar et al.,
2013).
4. Conclusion
The present results demonstrated that pumpkin oil may play an important role in the
protection against alcohol induced hepatotoxicity and oxidative stress. Pretreatment
with pumpkin oil may protect the liver from the hepatotoxic effect and oxidative stress
caused by alcohol. Further clinical studies are required to assess the benefits and
safety of pumpkin oil before use in human beings and approval by Food and Drug
administration (FDA).
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