Biomedicine & Preventive Nutrition 4 (2014) 8794

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Original article

Protective effect of lycopene on whole body irradiation induced liver

damage of Swiss albino mice: Pathological evaluation
Marimuthu Srinivasan a , Kalyanasundaram Banumathy Kalpana b , Nagarajan Devipriya b ,
Vanugopal Padmanaban Menon b,
a
Clinical Research, Ayurveda Research Institute for Mother and Child Health Care, Trivandrum 695 012, Kerala, India
b
Department of Biochemistry and Biotechnology, Centre for Micronutrient Research (John Hopkins University, USA Funded Center), Faculty of Science,
Annamalai University, Annamalainagar 608 002, Tamil Nadu, India

a r t i c l e i n f o a b s t r a c t

Article history: The present study was aimed to evaluate the radioprotective efcacy of lycopene, a naturally occurring
Received 14 June 2013 dietary carotenoid on whole body radiation-induced cellular damage in the liver of Swiss albino mice.
Accepted 28 June 2013 The rst phase of the study was carried out to x the effective concentration of lycopene by performing a
30 days survival studies using different graded doses (10, 20, 40 and 80 mg/kg body weight) of lycopene
Keywords: administered orally to mice via intragastric intubations for seven consecutive days prior to exposure
Lycopene of whole body radiation (10 Gy). Based on the results of survival studies, the effective dose of lycopene
X-ray radiation
was xed which was then administered to mice orally via intragastric intubations for 7 consecutive days
DNA damage
Oxidative stress
prior to exposure of whole body radiation (4 Gy) to evaluate its radioprotective efcacy by performing
Comet assay various biochemical estimations, comet assay, DNA fragmentation assay and histopathological alterations
in the liver of Swiss albino mice. The results indicated that radiation-induced decrease in the levels of
endogenous antioxidant enzymes and increase in lipid peroxidative index, DNA damage and comet assays
were altered by pre-administration with the effective dose of lycopene (20 mg/kg body weight) which
restored the antioxidant status to near normal and decreased the levels of lipid peroxidative index,
DNA damage and comet assays. These results were further conrmed by histopathological examinations,
which indicated that pre-administration with the effective dose of lycopene reduced the hepatic damage
induced by radiation. Thus the current study shows lycopene to be an effective radioprotector against
radiation-induced damage in the liver of mice.
2014 Published by Elsevier Masson SAS.

1. Introduction
Ionizing radiation has been found to produce deleterious effects
on biological systems; however this property of ionizing radiation
has been ingeniously exploited to an advantage in the treatment
of various neoplastic disorders in humans [1]. The major effect
of ionizing radiation is DNA damage brought about by direct and
indirect mechanisms. Whole body exposure to ionizing radiations
induces radiation sickness and syndromes depending on the expo-
sure dose [2]. If the dose of radiation is very high (i.e., 50 Gy),
it causes death within 48 h. It is characterized by ataxia, unco-
ordinated aberrant movements, tremors, convulsions, vomiting,
repeated defecation, watery diarrhea, nystagmus, meningisumus
and intermittent seizures [3]. In case of small animals like mice,
whole body irradiation with a dose between 5 and 10 Gy causes
Corresponding author. Tel.: +91 04144 238343; fax: +91 04144 239141.
E-mail addresses: srinimarimuthu@yahoo.co.in (M. Srinivasan),
biocmr@sify.com, cmrana@sify.com (V.P. Menon).
the gastrointestinal syndrome, and death within 310 days due to
failure of the gastrointestinal tract [4]. This is characterized by fever,
vomiting, anorexia, diarrhoea, infection, dehydration, weight loss,
diminishing food and water intake and decrease in gastric retention
and intestinal absorption. If the exposure dose is still lower (i.e.,
210 Gy), the death occurs within 30 days and is due to the fail-
ure of bone marrow, and the characteristics features include onset
of chills, fatigue, petechial hemorrhages in the skin and ulceration
of mouth, pharynx, and epilation [5]. Cutaneous injury also occurs
during radiation and is characterized by the loss of epidermis and,
at times, dermis [6]. Injuries to the skin might cover small areas
but extend deeply into the soft tissue, even reaching the under-
lying muscles and bone. This might be accompanied by profound
local edema, which places the patient at risk for a compartment
syndrome [7].
Currently there is a great deal of interest in the health benets of
carotenoids. Lycopene is a dietary carotenoid synthesized by plants
and microorganisms. Although most carotenoids are distributed in
a wide array of red fruits and vegetables, lycopene is contained
in relatively few foods. Over 85% of dietary lycopene is obtained

2210-5239/$ see front matter 2014 Published by Elsevier Masson SAS.

http://dx.doi.org/10.1016/j.bionut.2013.06.007
88 M. Srinivasan et al. / Biomedicine & Preventive Nutrition 4 (2014) 8794
from tomatoes and tomato products such as tomato juice, tomato
paste, sauce, ketchup and raw tomatoes [8]. The lycopene contents
of tomatoes and tomato products varies widely, up to threefold by
the variety of tomato and degree of ripeness, and heating lycopene-
rich foods with fat appears to increase its bioavailability. It also
occurs primarily in red fruits, vegetables, tomatoes, watermelon,
pink grape fruit, apricots, pink guava and papaya [9]. Lycopene has
the greatest ability of all the common carotenoids to quench singlet
oxygen, thus protecting against oxidative damage. In cell cultures,
lycopene is a more effective inhibitor of human endometrial, mam-
mary, and lung cancer cell proliferation than and -carotene [10].
Also a number of epidemiological studies have found associations
of lycopene consumption with a decreased risk of prostate cancer,
cervical intraepithelial neoplasia, stomach cancer, and pancreatic
cancer [11]. Thus, the aim of the present study was to evaluate
the radioprotective effect of lycopene on X-ray radiation-induced
cellular damage in the liver of Swiss albino mice.
2. Materials and methods
2.1. Chemicals
Lycopene, thiobarbituric acid, trichloroacetic acid, butylated
hydroxy toluene, 5,5 -dithio- bis-2 nitrobenzoic acid (DTNB), ethid-
ium bromide, sodium sarcosinate, high and low-melting-point
agarose, ethidium bromide, hydrogen peroxide, xanthine, NADPH,
EDTA and triton X-100 were purchased from Sigma Chemicals
(St.-Louis, MO, USA). All other chemicals and solvents were of ana-
lytical grade and obtained from S.D. Fine chemicals, Mumbai, India.
2.2. Experimental animals
Eight to ten weeks old male Swiss albino mice weighing 2530 g
bred in the Central Animal House (Institutional Ethics committee
number: 160/1999/CPCSEA), Rajah Muthiah Medical College, Tamil
Nadu, India were used in this study. The animals were fed on the
standard pellet diet (Agro Corporation Private Limited, Bangalore,
India) and water was given ad libitum.
Fig. 1. Dose dependent effect of lycopene on the survival rate of mice observed for an experimental duration of 30 days.
The animals were housed in plastic cages under controlled con-
dition of 14 h light/10 h dark cycles, 50% humidity and at 23 2 C.
The animals used in the present study were maintained in accor-
dance with the guidelines of the National Institute of Nutrition,
Indian Council for Medical Research, Hyderabad, India. This study
was approved by the Animal Ethical Committee, Annamalai Uni-
versity (Proposal Number: 641; dated 25.09.2009).
2.3. Preparation of lycopene and mode of administration
Lycopene (Cat. no.: L9879 M/S sigma chemical Co., St.-Louis,
USA) was dissolved in 0.2% dimethyl sulfoxide (DMSO) at different
concentrations (10, 20, 40, and 80 mg/kg body weight) and admin-
istered to mice once daily for seven consecutive days orally via
intragastric intubations. Seven days treatment was selected on the
basis of earlier study in which natural compounds showed their
radioprotective effects after seven days oral administration [12].
One hour after the last administration of lycopene on seventh day,
the animals were subjected to whole body exposure of 10 Gy X-
ray radiation [13]. The sham control group and radiation control
group received 0.2% DMSO via intragastric intubations. After irra-
diation, the animals were monitored for any symptoms of radiation
sickness and mortality twice daily for a period of 30 days.
2.4. Irradiation of mice
Animals were placed in polystyrene boxes and subjected to
whole body irradiation (via Dual energy linear accelerator unit or
LINAC) in the Department of Radiology, Dr. Kamakshi Memorial
Hospital, Chennai, Tamil nadu, India at a dose rate of 1.66 Gy/min.
During all irradiation procedures, the animals were kept in the dark
and under mild anesthesia (ketamine hydrochloride). This study
was also approved by the ethical committee of the hospital (Ref
No.: EC/2009; Dated: 07-08-09).
2.4.1. Study design 1: selection of optimum dose of lycopene
(n = 10)
Prior to the assessment of radioprotective potential of lycopene,
studies were carried out to x the optimum dose of lycopene. For
this, mice were categorized into six groups with 10 animals in each
 M. Srinivasan et al. / Biomedicine & Preventive Nutrition 4 (2014) 8794
group. Survival study was carried out for a period of 30 days to x
the effective concentration of lycopene against radiation-induced
toxicity.
Group 1 Sham control
Group 2 Radiation control (whole body exposure to 10 Gy radiation)
Group 3 to 6 Pre-administration with different graded doses (10, 20, 40
and 80 mg/kg body weight) of lycopene prior to whole
body exposure of 10 Gy radiation
2.4.2. Study design 2: investigation of the radioprotective efcacy
of lycopene (n = 8)
To ascertain the radioprotective ability of lycopene, the opti-
mum dose of lycopene (selected from study design 1) was
administered to mice prior to whole body exposure of 4 Gy radia-
tion treatment [14]. For this, mice were categorized into four groups
with eight animals in each group. The irradiation procedure and
preparation of drugs were similar as described under sections 2.3
and 2.4.
Group 1 Sham control
Group 2 Lycopene (20 mg/kg body weight)
Group 3 Radiation Control (whole body exposure to 4 Gy radiation)
Group 4 Pre-administration with effective dose (20 mg/kg body weight)
of lycopene prior to whole body exposure of 4 Gy radiation
Fig. 2. Changes in the activities of superoxide dismutase (A), catalase (B) and glutathione peroxidase (C) in sham control, lycopene (20 mg/kg body weight), 4 Gy radiation
and lycopene (20 mg/kg body weight) + 4 Gy radiation treated groups. Each bars represents mean S.D. of six experiments in each groups. **P < 0.05 indicates signicance
differences from X-ray irradiated group; one-way ANOVA followed by DMRT.
89
Animals were sacriced by cervical dislocation at 24 h
post-irradiation [24] and the liver was excised to study the radio-
protective effect of lycopene by performing various biochemical
assays, histopathological alterations and DNA fragmentation in the
liver and comet assay was analyzed in the blood [15].
2.5. Preparation of tissue homogenate
Liver samples were removed, cleared off blood and immedi-
ately transferred to ice-cold containers containing 0.9% saline. A
known amount of tissue was homogenized using appropriate buffer
(according to the assay procedures) in a tissue homogenizer.
2.5.1. Biochemical assays
For performing biochemical assays, a 10% liver homogenate
in 10 mM phosphate buffer was prepared, centrifuged at 800 g
for 5 min and the supernatant was used for the estimation of
superoxide dismutase, catalase, glutathione peroxidase, reduced
glutathione and thiobarbituric acid reactive substances using
standard spectrophotometric assays [1521]. Enzyme activity was
expressed as units/mg of protein where one unit of superox-
ide dismutase is dened as the amount of enzyme that inhibits
cytochrome c reduction by 50%; one unit of catalase as the amount
of enzyme degrading one micromole of H2 O2 per min and one unit
90 M. Srinivasan et al. / Biomedicine & Preventive Nutrition 4 (2014) 8794

of glutathione peroxidase as the amount of enzyme oxidizing one

micromole of NADPH per minute.

2.5.2. Comet assay

Blood from the tail of each animal was collected in heparinized
vials and two microscopic slides from the blood samples of each ani-
mal were prepared and processed for comet assay [22,23]. Briey,
the slides were immersed in lysis buffer at 4 C for 1 h and equili-
brated in alkaline solution for 20 min, followed by electrophoresis
for 30 min at 22 V, 299 mA. After electrophoresis, the slides were
neutralized and were stained with ethidium bromide (5 g/ml)
and visualized using a Nikon uorescent microscope. The images
(4555 cells/slide) were captured with high performance Nikon
camera. The quantication of the DNA strand breaks of the stored
images were done using the CASP software by which all comet
attributes (Tail length [TL], Tail moment [TM], Olive tail moment
[OTM], % DNA in tail) could be obtained directly.

2.5.3. DNA fragmentation assay

The DNA fragmentation assay in hepatic tissue was performed
according to the method of Mansour et al., [24]. In brief, genomic
DNA was quantied by measuring its absorbance at 260 nm. DNA
fragmentation assay was then studied by electrophoresis on a 2%
agarose gel and the pattern of fragmentation was visualized by a
gel documentation unit (Gel Doc, Bio Rad).

2.5.4. Histopathology
At the end of experimental period (24 h post-irradiation), the
animals were anaesthetized and intra-cardiac perfusion of nor-
mal saline followed by 10% formalin was done. The liver of all
groups were dissected out, xed and then stored in 10% formalin
solution. The prepared parafn blocks were later sectioned (5 m
sections) using a microtome, de-parafnated in xylene, passed
through alcohol, stained with haematoxylin-eosin, mounted in
neutral DPX medium, visualized under the microscope and the
images were captured using Nikon uorescent microscope (Nikon,
Fig. 3. Changes in the levels of reduced glutathione (A) and thiobarbituric acid
Tokyo, Japan). reactive substances (B) in sham control, lycopene (20 mg/kg body weight), 4 Gy radi-
ation and lycopene (20 mg/kg body weight) + 4 Gy radiation treated groups. Each
2.6. Statistical analysis bars represents mean S.D. of six experiments in each groups. **P < 0.05 indicates
signicance differences from X-ray irradiated group; one-way ANOVA followed by
DMRT.
All quantitative measurements were expressed as means S.D.
for sham control and experimental animals. The data were analyzed
using one way analysis of variance (ANOVA) on SPSS/PC* (statisti-
cal package for social sciences, personal computer) and the group and signicantly improved the survival rate of mice. Among the
means were compared by Duncans Multiple Range Test (DMRT). different concentrations, lycopene at the dose of 20 mg/kg body
The results were considered statistically signicant for P values less weight was found to offer optimum protection to mice against radi-
than 0.05. ation induced toxic effects by increasing the median survival period
to 15 days.
3. Results

3.1. Effect of lycopene on the survival rate of mice 3.2. Endogenous antioxidant status and lipid peroxidation

The results corresponding to the optimum protective dose of
lycopene on the survival rate of mice evaluated after whole body
exposure to a lethal dose of 10 Gy radiation is shown in Fig. 1. For
this, mice were pre-administered with different graded doses of
lycopene (10, 20, 40 and 80 mg/kg body weight/day) for 7 consec-
utive days prior to whole body exposure and monitored daily for a
period of 30 days. The results indicated that mice groups, which
received 10 Gy radiation showed signs of discomfort character-
ized by decreased physical activity and reduced uptake of food and
water. The radiation control group also exhibited signs of radiation
sickness such as irritability, rufing of hair, weight loss, emacia-
tion and epilation with a median survival period of only 6 days.
On the other hand, mice that were pre-administered with different
graded doses of lycopene reduced the signs of radiation sickness
The alteration in the levels of enzymatic antioxidants
(superoxide dismutase, catalase and glutathione peroxidase), non-
enzymatic antioxidant (reduced glutathione) and lipid peroxida-
tive index (thiobarbituric acid reactive substances) corresponding
to different groups of mice are shown in Figs. 2(AC) and 3(A, B). The
results indicated a signicant decrease in the activities of enzymatic
and non-enzymatic antioxidant status and an increase in the levels
of lipid peroxidative index (thiobarbituric acid reactive substances)
in the radiated groups. On the other hand, pre-administration of
lycopene modulated the effects of radiation by increasing the levels
of antioxidant status and decreasing the levels of thiobarbituric acid
reactive substances. In addition, lycopene alone pre-administered
group did not showed any alteration in the levels of antioxidant
status and lipid peroxidative index.
 M. Srinivasan et al. / Biomedicine & Preventive Nutrition 4 (2014) 8794 91

Fig. 4. Changes in the comet assay in tail of mice blood of sham control group (A), lycopene (20 mg/kg body weight) alone pre-administered group (B), 4 Gy radiation alone
treated group (C) and 4 Gy radiation + lycopene (20 mg/kg body weight) treated groups (D).

3.3. Comet assay 3.5. Histopathological Studies

The alteration in the levels of comet attributes analyzed in
the blood of different groups of mice is shown in Figs. 4(AD)
and 5(AD). The results indicated a prominent increase in the levels
of all comet attributes (tail length, tail moment, olive tail moment
and % DNA in the tail) in the radiated group when compared to
lycopene (20 mg/kg body weight) pre-administered group, which
modulated the effects of radiation by decreasing the levels of comet
attributes to a signicant level. In lycopene alone pre-administered
group, we observed no signicant increase in the comet formation
when compared to sham control group.
The histopathological changes observed in the liver of different
groups of mice are shown in Fig. 7(AD). The results indicated that
during radiation treatment, there was anisocytosis of hepatocytes
and some of the hepatocytes showed blast transformation, nuclear
disintegration and some have pyknotic nuclei. In the lycopene pre-
administered group, most of the hepatocytes are within normal
limits except for there is nuclear anisocytosis. The lycopene control
group did not showed any change in the hepatocytes indicating the
protective nature of the drug.

3.4. DNA Fragmentation assay
The result of DNA fragmentation assay performed in the hepatic
tissue of mice is shown in Fig. 6. The result indicated that in X-
ray irradiated group (L3), there was a signicant increase in the
formation of DNA fragments representative of the damage caused
by radiation in the liver of mice. Pre-administration of lycopene
(20 mg/kg body weight) prior to whole body exposure decreased
the formation of DNA fragments (L4) indicative of the protection
offered by lycopene in the liver of mice.
4. Discussion
Ionizing radiation has been shown to generate reactive oxy-
gen species (ROS) in a variety of cells [25]. When water, the most
abundant intracellular material, is exposed to ionizing radiation,
decomposition reactions occur and a variety of ROS intermedi-
ates are formed like superoxide, hydroxyl radicals, singlet oxygen,
and hydrogen peroxide [26]. The secondary radicals formed by the
interaction of hydroxyl radicals with organic molecules may also be
of importance [27]. These ROS have the potential to damage critical
cellular components such as DNA, proteins, and membrane lipids
92 M. Srinivasan et al. / Biomedicine & Preventive Nutrition 4 (2014) 8794

Fig. 5. Comet assay (A-D) performed in tail of mice blood to evaluate the DNA protecting ability of lycopene against radiation induced damage. Values are given as mean S.D.
of six experiments in each groups. **P < 0.05 indicates signicance differences from X-ray irradiated group; one-way ANOVA followed by DMRT.

which eventually lead to physical and chemically damage to tis-
sues ultimately resulting in cell death. Radiation exposure alters the
balance of endogenous protective system such as SOD, CAT, GPx and
GSH, vitamin E and C [28]. In our study, we observed a signicant
decrease in the activities of enzymic antioxidants and GSH in X-ray
irradiated mice. The endogenous antioxidant defenses are inade-
quate to reduce the radiation-induced free radicals. The decrease
may be due to the counterbalancing action of these enzymes against
radiation-induced ROS. Oral administration of lycopene restored
the activities of these enzymes in the liver of mice exposed to X-ray
radiation. Thus, lycopene contributes signicantly to the intracellu-
lar antioxidant defence system by acting as a powerful consumer of
superoxide anion and hydroxyl radicals, which induced oxidative
stress in the liver. The antioxidant enzymes and GSH are impor-
tant in providing protection from radiation exposure; the balance of
these enzymes in specic cell and in the whole organism is required
for maximum radioprotection [29]. In addition to its antioxidant
activity, lycopene has been shown to modulate phase II enzymes
like glutathione S-transferase (GST), glutathione reductase (GR)
and glutathione peroxidase (GPx), as well as GSH levels in experi-
mental models [30].
Radiation induced double stranded breaks is the most impor-
tant type of damage which leads to cell death. DNA is recognized
to be the primary target for ionizing radiation and this can pro-
duce cell death or mutation [28]. The decreased DNA fragment was
observed when the mice were pretreated with lycopene. Previous
studies have reported that lycopene supplementation decreases
77% of 8-oxodguo levels in Fe-NTA/ascorbate treated cells. These
results indicate that lycopene provided strong oxidation against
DNA-based oxidation [31]. Further consumption of tomato prod-
ucts was reported to reduce the susceptibility of lymphocyte DNA
to oxidative damage [32]. Silva et al. in 2001 also suggested that
pretreatment with carotenoid reduced the total number of chro-
mosomal aberrations induced by cisplatin treated rats [33].
Apart from DNA damage, lipid peroxidation is also considered as
one of the critical event resulting from the effect of ionizing radia-
tion [28]. Lipid peroxidation is a highly damaging event that results
from the interaction of ROS with cellular membranes. It not only
drastically alters the structure and function of membranes but also
generates highly toxic byproducts [29]. In the present study, it was
observed that there was a signicant increase in the levels of TBARS
in X-ray irradiated mice. Pretreatment of lycopene to X-ray irradi-
ated mice resulted in a decreased lipid peroxidation and improved
antioxidant status preventing the damage to the mice. Lycopene is
a lipophilic molecule containing 40 carbon atoms, highly unsatu-
rated, straight chain hydrocarbon made up off 11 conjugated and
two non-conjugated double bonds [34]. It passes easily through the
plasma membrane into the cytosol [35]. The presence of lycopene
in the cytosol, helps to scavenge the radiation-induced free radicals
and inhibits lipid peroxidation. This may be due to the antioxidant
sparing action of lycopene. It has also been stated that lycopene
inhibits cisplatin-induced lipid peroxidation in rat testes [36]. The
 M. Srinivasan et al. / Biomedicine & Preventive Nutrition 4 (2014) 8794
Fig. 6. DNA fragmentation assay performed in mouse liver tissue to evaluate the
DNA protecting ability of lycopene against radiation induced damage. L1- DNA
isolated from the liver of sham control group; L2- DNA isolated from the liver of
lycopene (20 mg/kg body weight) alone pre-administered group; L3-DNA isolated
from the liver of 4 Gy radiation alone treated group; L4-DNA isolated from the liver
of lycopene (20 mg/kg body weight) + radiation (4 Gy) treated groups.
Fig. 7. Histopathological examinations performed in mice liver. Sham control group (A); lycopene (20 mg/kg body weight) alone pre-administered group (B); 4 Gy radiation
alone treated group (C) and lycopene (20 mg/kg body weight) + 4 Gy radiation treated groups (D).
93
possible mechanism by which carotenoids quench singlet oxygen
(1 O2 ) and other excited species is as follows; during 1 O2 quenching
the energy is transferred from 1 O2 to the lycopene molecule, con-
verting it to the energy rich triplet state. Lycopene in the triplet state
can return to the ground state by dissipating the energy as heat or by
physical quenching, leaving the lycopene molecule intact and ready
for further quenching events [37]. Cantrell et al. [38] and Stahl et al.
[39] have reported that lycopene is also an excellent 1 O2 quencher
in biological membrane models, such as liposomes. Lycopene was
also the most rapidly destroyed carotenoid upon reaction with per-
oxyl radicals [40], indicating its presence in the rst line of defense.
Trapping of ROS, OH, NO2 or peroxynitrite, leads to oxidative
break down of the lycopene molecule. Thus, lycopene may protect
lipids, proteins and DNA from oxidative damage [41]. During sin-
glet oxygen (1 O2 ) quenching, energy is transferred from 1 O2 to the
lycopene molecule and the lycopene molecule is converted into
the energy rich triplet state. The energy rich lycopene molecule
scavenges other ROS, OH, NO2 or peroxynitrite. This might be
one of the antioxidant mechanisms for protecting the cells from
oxidative stress [41]. The histopathological results observed further
conrmed that lycopene due to its free radical scavenging proper-
ties and antioxidant nature preserved the integrity of tissue and
reduced the damage caused due to irradiation effect.
In whole body survival study, irradiated mice exhibited signs
of radiation sickness within 4 days after exposure to 10 Gy X-ray-
irradiation, which included reduction in food and water intake
and rufing of hairs. The death of 50% of the animals exposed to
10 Gy of radiation within 10 days might be due to functional fail-
ure of the gastrointestinal tract [42]. The remaining animals died
within the next 20 days might be due to hemopoietic syndrome
and characteristic syndrome like, irritability, weight loss, emacia-
tion, lethargy and rufing of hairs [43]. The highest protection was
observed at 20 mg/kg b.wt., of lycopene treatment (Fig. 1). Simi-
larly, triphala and cystone, the traditional herbal preparations, have
94 M. Srinivasan et al. / Biomedicine & Preventive Nutrition 4 (2014) 8794

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