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rna
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l J
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urna
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ea
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h Science
(
I
J
P
H
S)
Vo
l.
5
,
No
.
3
,
Sep
tem
b
er
201
6
,
p
p
.
2
8
4
~
2
9
3
I
SS
N:
2252
-
8806
284
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H
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d
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C
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p
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A
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:
Yu
n
ita
Sat
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a
P
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ati
w
i
,
Dep
ar
t
m
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Hea
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Scie
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J
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Mu
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m
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Un
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Kar
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No
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4
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J
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ast J
av
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d
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m
ail
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co
m
1.
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D
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Fo
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Ta
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1
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T
h
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m
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d
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to
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h
f
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b
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m
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ain
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a
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t
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[
2
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[
3
]
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T
h
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s
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f
f
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r
ad
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[
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p
ar
ticu
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p
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x
id
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(
O2
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-
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tr
o
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d
ca
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d
am
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ce
lls
[
5
]
.
B
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as
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m
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p
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OH
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l
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co
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s
i
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[
6
]
,
[
7
]
.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
J
P
HS
I
SS
N:
2252
-
8806
Hep
a
to
p
r
o
tective
E
ffect
o
f Ma
n
g
o
s
teen
P
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l E
xtra
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n
B
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x
-
I
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d
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ce
d
Ma
le
R
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ts
(
Yu
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ita
S
a
tya
P
r
a
tiw
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285
A
cc
o
r
d
in
g
to
th
e
r
esear
ch
r
esu
lt
s
,
liv
er
is
a
s
ite
w
h
er
e
b
o
r
ax
is
f
o
u
n
d
in
h
i
g
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co
n
ce
n
tr
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s
,
i
n
ad
d
itio
n
to
b
r
ain
an
d
k
id
n
e
y
s
[
8
]
.
T
h
e
liv
er
is
th
e
lar
g
est
o
r
g
an
w
h
er
e
m
an
y
p
r
o
ce
s
s
es
o
f
en
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y
m
e
tab
o
lis
m
,
lip
id
,
ca
r
b
o
h
y
d
r
ate
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d
p
r
o
tein
,
tak
e
p
lace
.
I
n
t
h
is
ca
s
e,
th
e
liv
er
is
ab
le
to
d
eto
x
x
e
n
o
b
io
tic
o
r
to
x
in
s
t
h
at
en
te
r
th
e
b
o
d
y
,
an
d
v
u
l
n
er
ab
le
to
th
e
ef
f
ec
ts
o
f
to
x
ic
s
u
b
s
ta
n
ce
s
[
9
]
,
[
1
0
]
.
T
h
e
f
in
d
i
n
g
o
f
b
o
r
ax
i
n
h
ig
h
co
n
ce
n
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n
s
i
n
t
h
e
li
v
er
w
il
l
ca
u
s
e
a
n
e
g
ati
v
e
i
m
p
ac
t
o
n
l
iv
er
ce
lls
.
Stu
d
ies
s
h
o
w
ed
th
at
d
e
g
en
er
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io
n
an
d
n
ec
r
o
s
is
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ad
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ea
d
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cc
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ed
in
e
x
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m
e
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ta
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v
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s
to
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ath
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d
ay
1
4
af
ter
b
o
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m
i
n
i
s
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atio
n
[
1
1
]
.
L
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d
a
m
ag
e
i
s
al
w
a
y
s
a
s
s
o
ciate
d
w
it
h
ce
ll
n
ec
r
o
s
is
,
in
cr
ea
s
ed
lip
id
p
er
o
x
id
atio
n
an
d
d
ec
r
ea
s
ed
lev
el
s
o
f
ti
s
s
u
e
G
SH
(
Gl
u
tat
h
io
n
e)
.
Ot
h
er
b
io
ch
e
m
ical
in
d
icato
r
s
in
b
lo
o
d
s
er
u
m
lev
el
ar
e
t
h
e
lev
e
l
o
f
SGOT
(
Ser
u
m
Gl
u
ta
m
ic
o
x
a
lo
ac
etic
tr
an
s
a
m
i
n
ase)
,
SGP
T
(
Ser
u
m
Gl
u
ta
m
ic
P
y
r
u
v
ate
T
r
an
s
a
m
in
a
s
e)
,
AL
P
(
A
l
k
ali
n
e
P
h
o
s
p
atase)
an
d
b
iliru
b
in
[
1
2
]
.
I
n
ad
d
itio
n
,
o
r
g
an
w
ei
g
h
ts
an
d
w
ei
g
h
t
lo
s
s
ar
e
in
d
icatio
n
o
f
o
r
g
an
in
j
u
r
y
.
C
h
a
n
g
es
i
n
o
r
g
an
w
ei
g
h
t
s
ha
v
e
lo
n
g
b
ee
n
ac
ce
p
ted
as a
s
en
s
it
iv
e
i
n
d
icato
r
o
f
ch
e
m
ical
ch
an
g
es i
n
o
r
g
a
n
s
[
1
3
]
,
[
1
4
]
.
I
n
r
elatio
n
s
to
t
h
e
o
cc
u
r
r
en
ce
o
f
h
ep
ato
to
x
icit
y
d
u
e
to
b
o
r
ax
i
n
d
u
ctio
n
i
n
m
ice,
it
is
n
e
ce
s
s
ar
y
to
p
r
o
tect
th
e
li
v
er
(
h
ep
ato
p
r
o
tectiv
e)
b
y
u
s
in
g
p
la
n
ts
co
n
tai
n
i
n
g
p
h
y
to
ch
e
m
ical
s
t
h
at
ca
n
s
er
v
e
as
an
tio
x
id
an
t
as
w
ell
a
s
f
r
ee
r
ad
icals sca
v
e
n
g
er
to
n
eu
tr
alize
f
r
ee
r
ad
icals a
n
d
ab
le
to
p
r
o
tect
co
en
zy
m
e
N
AD
+
lev
el.
T
h
is
s
t
u
d
y
u
s
ed
h
er
b
s
,
m
a
n
g
o
s
teen
p
ee
l
(
Ga
r
cin
ia
m
a
n
g
o
s
ta
n
a
L
in
n
)
,
w
h
ic
h
co
n
tai
n
h
ig
h
p
o
ly
p
h
en
o
ls
a
n
tio
x
id
an
t
s
k
i
n
d
,
s
u
ch
as
x
an
t
h
o
n
e
s
[
1
5
]
,
p
h
en
o
lic
ac
id
,
f
lav
o
n
o
id
s
[
1
6
]
,
c
atec
h
i
n
s
(
in
c
lu
d
i
n
g
f
la
v
o
n
o
id
)
,
h
ex
ad
ec
a
n
o
ic
ac
i
d
,
an
d
o
leic
ac
id
.
T
h
e
co
m
p
o
u
n
d
x
a
n
th
o
n
es
i
s
a
n
a
n
tio
x
id
a
n
t
f
o
u
n
d
in
m
an
g
o
s
tee
n
f
r
u
it
p
ee
l.
S
u
ch
co
m
p
o
u
n
d
s
h
av
e
a
n
tio
x
id
an
t
ac
ti
v
it
y
b
ec
a
u
s
e
o
f
i
ts
p
h
en
o
l
g
r
o
u
p
[
1
7
]
.
A
d
d
itio
n
al
l
y
,
m
an
g
o
s
tee
n
p
ee
l
co
n
tain
s
f
lav
o
n
o
id
s
th
at
i
s
s
u
p
p
o
s
ed
l
y
ab
le
to
p
r
o
tect
NA
D
+
lev
e
l
in
t
h
e
ce
ll
[
1
8
]
,
[
1
9
]
.
T
h
e
aim
o
f
t
h
is
s
t
u
d
y
w
a
s
to
d
eter
m
i
n
e
h
ep
ato
p
r
o
tectiv
e
ef
f
e
ct
o
f
m
an
g
o
s
tee
n
p
ee
l
ex
tr
ac
t
(
Ga
r
cin
ia
ma
n
g
o
s
ta
n
a
L
)
in
b
o
r
ax
-
i
n
d
u
ce
d
m
ale
r
at
s
(
R
a
ttu
s
n
o
r
ve
g
i
cu
s
)
b
y
m
ea
s
u
r
i
n
g
th
e
w
ei
g
h
t
o
f
t
h
e
liv
er
,
SGOT
an
d
SGP
T
.
2.
RE
S
E
ARCH
M
E
T
H
O
D
2
.
1
.
Resea
rc
h
t
y
pe
a
nd
des
ig
n
T
h
is
w
a
s
a
tr
u
e
e
x
p
er
i
m
e
n
t
al
s
tu
d
y
,
u
s
i
n
g
r
a
n
d
o
m
ized
s
ep
ar
ated
p
r
etest
-
p
o
s
ttes
t
co
n
tr
o
l
g
r
o
u
p
d
esig
n
.
T
h
er
e
w
e
r
e
t
h
r
ee
t
y
p
e
s
o
f
g
r
o
u
p
s
:
n
eg
at
iv
e
co
n
tr
o
l
g
r
o
u
p
{(
2
s
u
b
-
g
r
o
u
p
s
:
p
r
etes
t
(
K1
)
an
d
p
o
s
ttes
t
(
K2
)
},
p
o
s
itiv
e
co
n
tr
o
l
g
r
o
u
p
(
K3
)
an
d
m
an
g
o
s
tee
n
tr
ea
t
m
en
t
g
r
o
u
p
(
3
s
u
b
g
r
o
u
p
s
:
g
r
o
u
p
P
4
,
P
5
an
d
P
6
)
,
to
tall
y
t
h
er
e
w
er
e
6
g
r
o
u
p
s
.
2
.
2
.
Sa
m
ples
a
n
d sa
m
ple
s
ize
Sa
m
p
les
u
s
ed
w
er
e
w
h
ite
e
x
p
er
im
e
n
tal
r
at
s
(
R
a
ttu
s
n
o
r
ve
g
icu
s
)
o
f
W
is
tar
s
tr
ain
,
w
i
th
in
cl
u
s
io
n
cr
iter
ia
o
f
m
ale,
ag
ed
3
-
4
m
o
n
th
s
,
h
ea
l
th
y
an
d
ac
ti
v
e.
W
h
il
e
th
e
ex
cl
u
s
io
n
(
d
r
o
p
o
u
t)
cr
it
er
ia
w
er
e
u
n
w
ill
in
g
to
ea
t,
ill,
s
tr
es
s
,
in
ac
t
iv
e,
a
n
d
d
ied
b
ef
o
r
e
an
d
af
ter
o
b
t
ain
i
n
g
tr
ea
t
m
e
n
t.
T
h
er
e
w
er
e
s
i
x
s
tu
d
ied
g
r
o
u
p
s
(
K1
,
K2
,
K3
,
P
4
,
P
5
an
d
P
6
)
,
an
d
e
ac
h
g
r
o
u
p
ta
k
es 6
m
ice,
t
h
e
to
t
al
s
a
m
p
le
s
ize
w
a
s
3
6
r
ats.
2
.
3
.
H
er
bs
a
nd
ex
peri
m
e
nta
l a
nim
a
l
s
Ma
ter
ials
u
s
ed
w
er
e
d
ar
k
p
u
r
p
le
m
an
g
o
s
tee
n
f
r
u
it
f
r
o
m
m
a
n
g
o
s
tee
n
p
la
n
tatio
n
i
n
b
lac
k
f
r
o
m
T
r
en
g
g
lek
d
i
s
tr
ict.
Har
v
es
t
A
g
e
w
as 1
0
4
-
1
1
0
d
ay
s
af
ter
f
lo
wer
in
g
.
T
h
e
ex
p
er
im
e
n
tal
a
n
i
m
als
w
er
e
m
ale
W
is
tar
s
tr
ai
n
R
a
ttu
s
n
o
r
ve
g
icu
s
,
ag
ed
3
-
4
m
o
n
t
h
s
,
b
o
d
y
w
e
ig
h
t
r
an
g
ed
b
et
w
ee
n
1
5
0
-
2
5
0
g
,
p
u
r
ch
a
s
ed
f
r
o
m
a
r
ats
b
r
ee
d
er
in
B
an
g
il,
P
asu
r
u
a
n
,
u
n
d
er
th
e
s
u
p
er
v
i
s
io
n
o
f
t
h
e
Facu
lt
y
o
f
Vete
r
i
n
ar
y
Me
d
ici
n
e,
Un
i
v
er
s
it
y
o
f
A
ir
la
n
g
g
a,
Su
r
ab
a
y
a.
R
at
f
ee
d
w
as
p
elle
t
p
r
o
d
u
ce
d
b
y
P
T
.
C
h
ar
o
en
P
o
k
p
h
an
d
Su
r
ab
a
y
a.
R
ats
'
d
r
in
k
in
g
w
a
ter
w
as
g
al
lo
n
w
ater
o
f
t
h
e
b
r
an
d
A
q
u
a.
B
e
f
o
r
e
tr
ea
t
m
e
n
t,
th
e
ex
p
er
i
m
e
n
tal
a
n
i
m
als
w
er
e
a
cc
li
m
atize
d
f
o
r
1
6
d
ay
s
d
u
r
i
n
g
w
h
ic
h
t
h
e
y
w
er
e
g
i
v
e
n
w
it
h
s
tan
d
ar
d
f
ee
d
,
ad
lib
itu
m
d
r
in
k
,
a
m
b
ie
n
t te
m
p
er
atu
r
e,
air
h
u
m
id
it
y
b
et
w
ee
n
4
0
-
6
0
%.
2
.
4
.
Che
m
ica
l
s
ub
s
t
a
nce
s
a
nd
ins
t
ru
m
ent
s
C
h
e
m
ical
s
f
o
r
p
r
o
d
u
cin
g
m
a
n
g
o
s
teen
p
ee
l
ex
tr
ac
t
i
n
clu
d
e
s
a
s
ter
ile
d
is
till
ed
w
ater
,
5
0
%
eth
a
n
o
l,
C
MC
-
Na
(
C
ar
b
o
x
y
m
e
th
y
l
ce
l
lu
lo
s
e)
f
o
r
s
tab
ilizi
n
g
a
s
o
lu
t
io
n
o
f
m
a
n
g
o
s
tee
n
p
ee
l
ex
tr
a
ct,
b
o
r
ax
(
s
o
d
iu
m
tetr
ab
o
r
ate
d
ec
ah
y
d
r
ate)
,
ch
lo
r
o
f
o
r
m
f
o
r
r
ats
an
est
h
es
ia,
an
d
1
0
%
f
o
r
m
a
ld
eh
y
d
e
b
u
f
f
er
to
p
r
eser
v
e
r
at
o
r
g
an
s
.
As
f
o
r
th
e
p
h
y
to
ch
e
m
icals
(
p
o
ly
p
h
en
o
ls
a
n
d
f
lav
o
n
o
id
s
)
s
cr
ee
n
in
g
o
f
m
a
n
g
o
s
tee
n
p
ee
l
f
iltra
te
w
e
u
s
ed
ch
lo
r
o
f
o
r
m
-
eth
y
l
ac
eta
te
-
f
o
r
m
ic
ac
id
,
FeC
l3
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ch
lo
r
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f
o
r
m
-
m
e
th
an
o
l,
a
n
d
a
m
m
o
n
ia
v
ap
o
r
s
.
Fo
r
th
e
an
a
l
y
s
is
o
f
SGOT
an
d
SGPT
v
alu
es,
th
e
ch
e
m
ical
m
ater
ial
s
w
er
e
as
s
a
y
b
u
f
f
er
,
L
DH,
co
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s
tr
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NADH
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r
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t,
d
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i
n
s
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m
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ed
w
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ca
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(
co
n
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g
3
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4
m
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,
s
u
r
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s
cis
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s
ca
lp
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t
w
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p
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ca
le
s
,
o
r
g
an
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ca
l
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elec
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ca
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ze
d
r
y
er
E
y
ela
m
o
d
el
o
f
FD
-
8
1
,
San
y
o
u
ltra
lo
w
Fre
ez
er
,
g
r
a
m
s
ca
le
s
,
an
d
an
an
a
l
y
t
ical
b
alan
ce
.
2
.
5
.
M
a
ng
o
s
t
e
e
n pee
l e
x
t
ra
ct
a
nd
do
s
es
T
h
e
m
a
k
i
n
g
o
f
m
a
n
g
o
s
tee
n
p
ee
l
ex
tr
ac
t
(
MP
E
)
u
s
ed
m
ac
er
atio
n
an
d
s
o
n
icat
io
n
m
eth
o
d
s
,
w
it
h
a
p
o
lar
s
o
lv
en
t
o
f
5
0
%
et
h
a
n
o
l.
As
m
u
ch
as
5
0
0
m
g
m
a
n
g
o
s
t
ee
n
p
ee
l
p
o
w
d
er
,
w
h
o
s
e
t
h
e
o
u
ter
p
ee
l
h
ad
b
ee
n
r
e
m
o
v
ed
,
w
a
s
m
i
x
ed
w
it
h
2
L
o
f
5
0
%
et
h
an
o
l
u
n
til
it
b
ec
am
e
h
o
m
o
g
en
eo
u
s
,
d
ep
o
s
ited
f
o
r
2
4
h
o
u
r
s
(
m
ac
er
atio
n
p
r
o
ce
s
s
)
,
s
o
n
icate
d
f
o
r
1
5
m
i
n
u
tes
a
n
d
f
ilter
ed
.
I
t
w
a
s
r
ep
ea
ted
5
ti
m
es
to
f
o
r
m
t
h
e
f
il
tr
ate.
T
h
en
it
w
as
e
v
ap
o
r
ated
w
it
h
r
o
tav
a
p
o
u
r
(
4
5
º
C
)
to
f
o
r
m
a
v
i
s
co
u
s
ex
tr
ac
t.
F
u
r
th
er
m
o
r
e,
it
w
a
s
f
r
ee
ze
d
r
ied
f
o
r
2
4
h
o
u
r
s
,
w
h
ic
h
e
v
e
n
t
u
all
y
t
h
e
e
x
tr
ac
t
w
a
s
f
o
r
m
ed
i
n
t
h
e
f
o
r
m
o
f
d
r
y
p
o
w
d
er
.
T
h
e
y
ield
w
a
s
1
5
%
f
o
r
m
ed
.
T
h
e
d
o
s
e
ap
p
lied
w
as 2
0
0
m
g
/k
g
,
4
0
0
m
g
/
k
g
an
d
6
0
0
m
g
/
k
g
r
at
B
W
.
2
.
6
.
B
o
ra
x
s
o
lutio
n a
nd
do
s
es
B
o
r
ax
u
s
ed
h
as
a
ch
e
m
ica
l
ter
m
s
o
d
iu
m
tetr
ab
o
r
ate
d
ec
ah
y
d
r
ate,
as
a
w
h
ite
p
o
w
d
er
in
t
h
e
s
o
lv
e
n
t
o
f
d
is
till
ed
w
ater
,
m
i
x
ed
u
n
til
h
o
m
o
g
en
eo
u
s
.
B
o
r
ax
d
o
s
e
ap
p
lied
w
a
s
ap
p
r
o
x
i
m
atel
y
2
6
1
.
1
m
g
/k
g
o
f
r
at
b
o
d
y
w
ei
g
h
t/d
a
y
.
2
.
7
.
P
re
pa
ra
t
io
ns
f
o
r
t
re
a
t
m
ent
P
r
ep
ar
atio
n
MP
E
g
i
v
e
n
w
i
th
s
o
n
d
e
to
th
e
m
ice
ar
e
w
as
MP
E
s
u
s
p
e
n
s
io
n
i
n
C
M
C
-
Na
(
C
ar
b
o
x
y
Me
th
y
l Cell
u
lo
s
e
-
So
d
i
u
m
)
0
.
5
%.
2
.
8
.
P
ro
ce
du
re
B
ef
o
r
e
th
e
in
ter
v
e
n
tio
n
,
p
r
etes
t n
e
g
ati
v
e
co
n
tr
o
l
m
ice
(
K1
)
w
a
s
n
o
t
g
i
v
en
an
y
t
h
i
n
g
.
P
o
s
ttes
t
n
eg
a
tiv
e
co
n
tr
o
l
(
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)
w
as
g
i
v
en
o
n
l
y
w
it
h
0
.
5
%
C
MC
-
Na
s
o
lu
tio
n
,
s
tar
tin
g
o
n
d
a
y
1
to
1
6
.
T
h
e
p
o
s
itiv
e
co
n
tr
o
l
(
K3
)
w
a
s
g
i
v
en
o
n
l
y
w
i
th
b
o
r
ax
s
o
l
u
tio
n
to
d
a
y
1
6
.
T
r
ea
tm
e
n
t
i
n
th
e
th
r
ee
g
r
o
u
p
s
o
f
r
ats
w
it
h
b
o
r
ax
(
f
r
o
m
d
a
y
1
to
d
ay
1
6
)
w
a
s
f
o
llo
w
ed
w
i
th
t
h
e
p
r
o
v
is
io
n
o
f
MP
E
s
tar
ti
n
g
o
n
d
ay
3
to
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6
u
s
i
n
g
a
s
to
m
ac
h
s
o
n
d
e
in
3
d
o
s
es
o
f
2
0
0
m
g
/
k
g
b
w
(
P
4
)
,
4
0
0
m
g
/
k
g
b
w
(
P
5
)
an
d
6
0
0
m
g
/
k
g
b
w
(
P
6
)
,
1
-
2
m
l
p
er
r
at.
P
r
etest
o
f
d
ay
0
an
d
p
o
s
ttes
t
o
f
d
a
y
1
7
w
as d
o
n
e
b
y
s
ca
lin
g
liv
er
w
eig
h
t,
a
n
d
m
ea
s
u
r
i
n
g
S
GPT
an
d
SGOT
lev
els in
t
h
eir
b
lo
o
d
s
er
u
m
.
2
.
9
.
SG
O
T
a
n
d S
G
P
T
t
est
m
et
h
o
ds
SGOT
ex
a
m
i
n
atio
n
p
r
o
ce
d
u
r
e,
d
ir
ec
t
ly
b
y
m
ea
s
u
r
in
g
A
ST
(
asp
ar
tate
tr
an
s
a
m
i
n
ase)
ac
ti
v
it
y
b
ased
o
n
th
e
a
m
o
u
n
t
o
f
o
x
alo
ac
etate
p
r
o
d
u
ce
d
b
y
AST
.
I
n
th
i
s
te
s
t
,
o
x
alo
ac
etate
an
d
N
ADH
wer
e
co
n
v
er
ted
i
n
to
m
alate
a
n
d
N
A
D
b
y
m
a
late
d
eh
y
d
r
o
g
e
n
ase
e
n
z
y
m
e.
Dec
r
e
ased
lev
el
s
o
f
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at
3
4
0
n
m
ab
s
o
r
b
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ce
w
a
s
p
r
o
p
o
r
tio
n
al
an
d
in
ac
co
r
d
an
ce
w
it
h
t
h
e
A
ST
ac
tiv
i
t
y
.
W
o
r
k
in
g
s
ta
g
e
s
w
er
e
th
r
ee
:
s
tag
e
o
f
u
s
in
g
9
6
w
e
ll
s
p
late,
s
tag
e
o
f
u
s
i
n
g
cu
v
ettes,
an
d
s
tag
e
o
f
m
ea
s
u
r
e
m
e
n
t.
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T
ex
am
in
at
io
n
p
r
o
ce
d
u
r
e,
in
d
ir
ec
tl
y
b
y
m
ea
s
u
r
in
g
t
h
e
ac
tiv
it
y
o
f
AL
T
(
A
lan
in
e
tr
an
s
a
m
i
n
ase
)
b
ased
o
n
t
h
e
a
m
o
u
n
t
o
f
p
y
r
u
v
ate
p
r
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d
u
ce
d
b
y
AL
T
.
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n
t
h
i
s
tes
t,
p
y
r
u
v
ate
a
n
d
N
A
DH
w
er
e
co
n
v
er
ted
in
to
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te
a
n
d
N
A
D
b
y
t
h
e
en
z
y
m
e
lacta
te
d
eh
y
d
r
o
g
en
a
s
e
(
L
DH)
.
Dec
r
ea
s
ed
le
v
els
o
f
NADH
at
3
4
0
n
m
ab
s
o
r
b
an
ce
w
as
p
r
o
p
o
r
tio
n
al
to
th
e
A
L
T
ac
tiv
i
t
y
.
W
o
r
k
i
n
g
s
tag
e
s
w
er
e
th
r
ee
:
s
tag
e
o
f
u
s
in
g
9
6
p
late
w
ell
s
,
s
tag
e
o
f
u
s
in
g
cu
v
ette
s
,
an
d
s
t
ag
es o
f
m
ea
s
u
r
e
m
en
t.
2
.
1
0
.
Sta
t
is
t
ica
l a
na
ly
s
is
Data
an
al
y
s
is
w
a
s
p
er
f
o
r
m
ed
u
s
i
n
g
I
B
M
SP
SS
s
tatis
tics
2
1
f
o
r
w
in
d
o
w
s
as
f
o
llo
w
s
:
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an
al
y
s
i
s
w
i
t
h
d
escr
ip
tiv
e
s
tati
s
tic
s
,
b
)
test
f
o
r
n
o
r
m
alit
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o
f
d
ata
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is
tr
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tio
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w
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th
t
h
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Ko
l
m
o
g
o
r
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test
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h
o
m
o
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t
b
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v
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test
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test
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3.
RE
SU
L
T
S
A
ND
AN
AL
Y
SI
S
3
.
1
.
L
iv
er
w
eig
ht
R
es
u
lts
o
f
m
ea
s
u
r
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m
e
n
ts
o
f
t
h
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w
ei
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h
t
a
v
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h
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liv
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r
in
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ch
s
tu
d
y
g
r
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u
p
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p
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ted
i
n
T
ab
le
1
.
W
e
ca
n
s
ee
b
elo
w
th
i
s
.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
J
P
HS
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N:
2252
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Hep
a
to
p
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Ma
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Yu
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tiw
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287
T
ab
le
1
.
W
eig
h
t
A
v
er
ag
e
o
f
th
e
L
I
VE
R
i
n
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ch
S
tu
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ied
Gr
o
u
p
s
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o
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t
u
d
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d
g
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u
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x
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7
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0
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2
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K2
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6
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T
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ig
n
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f
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el
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o
f
Kr
u
s
k
al
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m
p
ar
ati
v
e
te
s
t
is
0
.
4
3
5
(
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>
0
.
0
5
)
.
No
tes:
K1
=
p
r
etest n
eg
at
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co
n
tr
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l g
r
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p
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n
o
t r
ec
eiv
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g
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i
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g
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n
d
a
y
0
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=
p
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s
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t n
e
g
ati
v
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co
n
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f
0
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5
% C
MC
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f
r
o
m
d
a
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to
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r
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b
w
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a
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ay
1
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tr
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t
m
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n
t
g
r
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p
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b
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1
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1
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g
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r
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d
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ay
1
6
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m
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L
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y
,
s
u
c
h
as
s
k
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l
m
u
s
c
l
e
[
2
1
]
.
B
o
r
ax
h
as
ch
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m
ical
p
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ties
th
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[
6
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[
7
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.
I
m
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ts
[
2
2
]
.
Evaluation Warning : The document was created with Spire.PDF for Python.
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Vo
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5
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3
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Sep
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b
er
201
6
:
2
8
4
–
2
9
3
288
T
h
e
in
cr
ea
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a
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m
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An
al
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s
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f
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to
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ar
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f
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f
ch
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[
2
3
]
.
Descr
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,
a
f
ter
1
6
d
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tio
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h
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ats
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6
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ll
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s
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n
g
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ca
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lead
to
a
n
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tain
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D
+
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[
1
8
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[
1
9
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,
s
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t
A
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P
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a
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p
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s
w
elli
n
g
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T
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lo
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t (
th
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b
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g
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3
.
2
.
SG
O
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R
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av
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An
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A
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Ser
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Gr
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A
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x
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2
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3
3
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3
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6
3
T
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(
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A
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0
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0
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(
α
<
0
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5
)
.
T
ab
le
3
.
R
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lts
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"T
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5
3
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9
9
3
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1
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9
9
7
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c
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1
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0
4
0
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c
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6
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2
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K3
0
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2
0
8
N
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f
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c
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2
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8
5
5
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f
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c
a
n
t
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d
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f
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t
8
K
2
–
P5
0
.
2
7
3
N
o
t
si
g
n
i
f
i
c
a
n
t
l
y
d
i
f
f
e
r
e
n
t
9
K
2
–
P6
0
.
7
0
8
N
o
t
si
g
n
i
f
i
c
a
n
t
l
y
d
i
f
f
e
r
e
n
t
10
K
3
–
P4
0
.
0
1
7
S
i
g
n
i
f
i
c
a
n
t
l
y
d
i
f
f
e
r
e
n
t
11
K
3
–
P5
0
.
0
0
1
S
i
g
n
i
f
i
c
a
n
t
l
y
d
i
f
f
e
r
e
n
t
12
K
3
–
P6
0
.
9
4
0
N
o
t
si
g
n
i
f
i
c
a
n
t
l
y
d
i
f
f
e
r
e
n
t
13
P
4
–
P5
0
.
9
0
3
N
o
t
si
g
n
i
f
i
c
a
n
t
l
y
d
i
f
f
e
r
e
n
t
14
P
4
–
P6
0
.
1
3
3
N
o
t
si
g
n
i
f
i
c
a
n
t
l
y
d
i
f
f
e
r
e
n
t
15
P
5
–
P6
0
.
0
1
3
S
i
g
n
i
f
i
c
a
n
t
l
y
d
i
f
f
e
r
e
n
t
N
o
t
e
s
:
a
)
<
0
.
0
5
=
s
i
g
n
i
f
i
c
a
n
t
d
i
f
f
e
r
e
n
c
e
b
)
>
0
.
0
5
=
n
o
t
si
g
n
i
f
i
c
a
n
t
d
i
f
f
e
r
e
n
ce
T
h
e
co
m
p
lete
r
es
u
lt
s
o
f
SGO
T
m
ea
s
u
r
e
m
e
n
t
s
ar
e
p
r
esen
te
d
in
F
i
g
u
r
e
2
.
B
ased
o
n
th
e
r
e
s
u
lt
s
o
f
th
e
s
tu
d
y
,
b
lo
o
d
s
er
u
m
lev
e
ls
o
f
AST
in
all
s
t
u
d
y
g
r
o
u
p
s
w
er
e
s
ig
n
i
f
ica
n
tl
y
d
if
f
er
e
n
t
(
α
=
0
.
0
0
o
r
α
<
0
.
0
5
)
.
T
h
u
s
,
th
er
e
w
as
a
s
i
g
n
if
ican
t
h
ep
ato
p
r
o
tectiv
e
ef
f
ec
t
o
f
MP
E
o
n
t
h
e
d
ec
lin
e
i
n
b
lo
o
d
s
er
u
m
le
v
el
s
o
f
AST
m
ice
t
h
at
h
av
e
b
ee
n
in
d
u
ce
d
w
ith
b
o
r
ax
f
o
r
1
6
d
ay
s
.
T
h
e
h
ig
h
e
s
t
a
v
er
ag
e
le
v
el
(
1
2
5
.
0
0
±
1
4
.
8
5
U/L
)
w
as
s
till
i
n
p
o
s
itiv
e
co
n
tr
o
l
g
r
o
u
p
(
r
ec
ei
v
in
g
o
n
l
y
b
o
r
ax
f
o
r
1
6
d
a
y
s
)
.
A
ST
lev
el
w
as
th
e
lo
w
e
s
t
(
th
e
b
est)
i
n
t
h
e
p
r
o
v
is
io
n
o
f
MP
E
o
f
4
0
0
m
g
/
k
b
b
w
(
8
7
.
0
0
±
1
2
.
6
3
)
U/L
.
Fu
n
ct
io
n
all
y
,
r
at
'
s
li
v
er
f
u
n
c
tio
n
w
as
s
till
r
elati
v
el
y
n
o
r
m
al,
b
ec
au
s
e
t
h
e
n
o
r
m
al
S
GOT
v
alu
e
in
m
ale
r
ats i
s
6
0
-
3
0
0
U/L
,
an
d
f
e
m
a
le
8
0
-
2
5
0
U/L
[
2
4
]
.
T
h
e
en
z
y
m
e
a
m
i
n
o
tr
an
s
f
er
a
s
e
(
f
o
r
m
er
l
y
tr
a
n
s
a
m
i
n
ase)
is
m
o
s
t
o
f
t
en
u
s
ed
as
a
s
p
ec
i
f
ic
i
n
d
icato
r
o
f
h
ep
ato
-
ce
ll
u
lar
n
ec
r
o
s
is
.
T
h
e
en
z
y
m
e
asp
ar
tate
a
m
i
n
o
tr
an
s
f
er
ase
(
A
ST
,
f
o
r
m
er
l
y
s
er
u
m
g
l
u
ta
m
ic
o
k
s
a
lo
-
ac
etate
tr
an
s
a
m
in
a
s
e
o
r
SG
OT
)
an
d
alan
in
e
a
m
in
o
tr
a
n
s
f
er
ase
(
AL
T
,
f
o
r
m
er
l
y
s
er
u
m
g
l
u
ta
m
ic
p
y
r
u
v
ic
tr
an
s
a
m
i
n
ase
o
r
SGP
T
)
c
ataly
ze
s
th
e
tr
an
s
f
er
o
f
a
m
in
o
g
r
o
u
p
o
f
asp
ar
tic
ac
id
an
d
alan
in
e
r
esp
ec
tiv
el
y
to
t
h
e
k
eto
g
r
o
u
p
o
f
k
eto
g
l
u
tar
ic
ac
id
.
A
L
T
is
m
ai
n
l
y
lo
ca
lized
in
th
e
li
v
er
b
u
t
A
ST
is
p
r
esen
t
in
v
ar
io
u
s
tis
s
u
e
s
s
u
c
h
as t
h
e
h
ea
r
t,
s
k
eleta
l
m
u
s
cles,
k
id
n
e
y
,
b
r
ain
an
d
li
v
er
[
2
5
]
,
[
2
6
]
.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
J
P
HS
I
SS
N:
2252
-
8806
Hep
a
to
p
r
o
tective
E
ffect
o
f Ma
n
g
o
s
teen
P
ee
l E
xtra
ct
o
n
B
o
r
a
x
-
I
n
d
u
ce
d
Ma
le
R
a
ts
(
Yu
n
ita
S
a
tya
P
r
a
tiw
i)
289
Fig
u
r
e
2
.
R
esu
lts
o
f
SGOT
m
e
asu
r
e
m
en
t
a
n
d
th
e
a
v
er
ag
e
i
n
r
ats s
er
u
m
T
h
e
r
esu
lts
o
f
a
s
tu
d
y
b
y
Octa
v
ia
(
2
0
1
2
)
[
1
1
]
,
th
at
ex
a
m
i
n
ed
th
e
ef
f
ec
t
o
f
b
o
r
ax
o
n
h
is
to
p
a
th
o
lo
g
ical
p
r
o
f
ile
o
f
th
e
liv
er
in
w
h
ite
r
a
ts
(
R
a
ttu
s
n
o
r
ve
g
icu
s
)
,
u
s
in
g
ex
p
er
i
m
e
n
t
u
p
to
d
ay
1
4
o
f
in
ter
v
en
t
io
n
,
s
h
o
w
ed
th
at
b
o
r
ax
d
o
es
n
o
t
ca
u
s
e
c
o
n
g
es
t
io
n
,
b
u
t
ca
u
s
ed
d
eg
en
er
ativ
e
ch
a
n
g
e
s
an
d
n
ec
r
o
s
i
s
in
liv
er
ce
lls
.
An
d
Ast
i
n
in
g
r
u
m
(
2
0
1
1
)
[
2
7
]
s
tu
d
ied
ab
o
u
t
th
e
ef
f
ec
t
o
f
b
o
r
ax
o
n
li
v
er
d
a
m
a
g
e
s
w
i
s
s
W
eb
s
ter
s
tr
ai
n
o
f
m
ale
m
ice
,
i
n
w
h
ic
h
b
o
r
ax
w
as
ad
m
i
n
is
ter
ed
i
n
d
o
s
es
o
f
1
5
0
,
3
0
0
,
4
5
0
,
an
d
6
0
0
m
g
/k
g
/d
a
y
f
o
r
2
7
d
ay
s
,
ev
id
e
n
tl
y
in
d
o
s
e
o
f
6
0
0
m
g
/
k
g
/d
a
y
w
as
f
o
u
n
d
to
in
cr
ea
s
e
SGOT
(
A
ST
)
an
d
SGOT
(
A
L
T
)
lev
els i
n
m
ice
li
v
er
.
AST
is
p
r
esen
t
i
n
b
o
th
m
ito
c
h
o
n
d
r
ia
an
d
c
y
to
s
o
l
o
f
h
ep
at
o
cy
te
s
.
AL
T
is
lo
ca
lized
to
th
e
c
y
to
s
o
l
[
2
6
]
,
[
2
8
]
.
In
c
y
to
s
o
lic
a
n
d
m
ito
ch
o
n
d
r
ia,
AST
w
as
a
tr
u
e
is
o
e
n
z
y
m
e
a
n
d
i
m
u
n
o
lo
g
icall
y
d
is
tin
c
t
[2
9
].
A
p
p
r
o
x
i
m
atel
y
8
0
%
o
f
A
ST
ac
tiv
it
y
i
n
h
u
m
an
li
v
er
i
s
co
n
tr
ib
u
ted
b
y
m
ito
ch
o
n
d
r
ial
i
s
o
en
z
y
m
e,
w
h
er
ea
s
m
o
s
t
A
ST
ac
tiv
it
ies cir
cu
lati
n
g
in
n
o
r
m
al
i
n
d
iv
id
u
als ar
e
d
e
r
iv
ed
f
r
o
m
c
y
to
s
o
lic
is
o
e
n
z
y
m
es
[
2
5
]
,
[
30
]
.
AL
T
cy
to
s
o
l
is
ass
o
ciate
d
w
i
th
p
y
r
u
v
ate
u
s
e
in
g
l
y
co
l
y
s
is
.
AL
T
m
ito
c
h
o
n
d
r
ial
is
i
n
v
o
l
v
ed
in
th
e
co
n
v
er
s
io
n
o
f
ala
n
i
n
e
to
p
y
r
u
v
ate
in
g
lu
co
n
eo
g
e
n
esi
s
,
an
d
AST
p
lay
s
a
n
i
m
p
o
r
tan
t r
o
le
in
t
r
an
s
p
o
r
t a
cr
o
s
s
th
e
m
ito
ch
o
n
d
r
ial
m
e
m
b
r
a
n
e
[
3
1
]
,
[
3
2
].
Hep
ato
ce
l
lu
lar
d
a
m
a
g
e
d
u
e
to
a
n
y
d
is
o
r
d
er
allo
w
s
p
las
m
a
m
e
m
b
r
a
n
e
leak
ag
e,
s
o
th
at
i
n
tr
ac
ell
u
lar
en
z
y
m
es
s
u
c
h
as
AL
T
o
r
AST
f
lo
w
i
n
to
th
e
b
lo
o
d
s
tr
ea
m
.
Du
e
to
s
o
m
e
h
ep
ato
to
x
ican
ts
,
t
h
e
in
cr
ea
s
e
o
f
li
v
er
a
m
i
n
o
tr
an
s
f
er
ase
s
y
n
t
h
esi
s
al
s
o
b
ec
o
m
es
a
s
o
u
r
ce
o
f
ele
v
ated
le
v
els
o
f
s
er
u
m
e
n
z
y
m
e
in
h
ep
ato
ce
llu
l
ar
in
j
u
r
y
[
3
3
]
.
I
n
cr
ea
s
ed
lev
els
o
f
s
er
u
m
A
ST
o
cc
u
r
s
in
m
it
o
ch
o
n
d
r
ia
af
ter
an
ex
ten
s
i
v
e
tis
s
u
e
n
ec
r
o
s
is
.
T
h
er
ef
o
r
e,
m
ito
c
h
o
n
d
r
ial
A
ST
d
eter
m
i
n
atio
n
is
r
ec
o
m
m
en
d
ed
in
m
io
ca
r
d
ial
in
f
ar
ctio
n
ca
s
e
s
an
d
is
al
s
o
elev
ated
in
c
h
r
o
n
ic
li
v
er
d
is
ea
s
e
[3
4
].
Nec
r
o
s
is
o
f
th
e
l
iv
er
tis
s
u
e
o
cc
u
r
s
d
u
e
to
o
x
id
ati
v
e
s
tr
ess
.
Ox
id
ati
v
e
s
tr
es
s
o
cc
u
r
s
d
u
e
t
o
ex
ce
s
s
i
v
e
g
en
er
atio
n
o
f
f
r
ee
r
ad
icals a
n
d
/o
r
lack
o
f
an
tio
x
id
an
ts
(
e
g
,
a
s
u
b
s
ta
n
ce
ca
l
led
g
l
u
tat
h
io
n
e,
v
ita
m
i
n
A
a
n
d
E
)
to
b
in
d
th
e
r
ad
ical
s
.
O
x
id
ativ
e
s
tr
ess
o
cc
u
r
s
i
n
co
n
j
u
n
ctio
n
w
it
h
th
e
A
T
P
d
ep
letio
n
an
d
r
ed
u
ce
d
g
l
u
tath
io
n
e
lev
els i
n
t
h
e
ce
lls
[
3
5
].
T
h
e
ten
d
en
c
y
o
f
AST
d
ec
r
e
ase
in
b
lo
o
d
s
er
u
m
in
m
ice
is
t
h
o
u
g
h
t
to
r
es
u
lt
f
r
o
m
p
o
ly
p
h
en
o
l
s
co
n
tr
ib
u
tio
n
o
f
m
an
g
o
s
tee
n
p
ee
l
ex
tr
ac
t
as
an
tio
x
id
a
n
ts
o
r
s
ca
v
e
n
g
er
o
f
f
r
ee
r
ad
icals
th
a
t
p
r
ev
en
t
o
x
id
ativ
e
s
tr
ess
i
n
m
ice
liv
er
,
w
h
ic
h
w
ill
r
esu
lt i
n
liv
er
n
ec
r
o
s
is
.
P
o
ly
p
h
e
n
o
l
i
s
a
g
r
o
u
p
o
f
s
ec
o
n
d
ar
y
m
etab
o
lites
i
n
v
o
l
v
ed
i
n
th
e
clea
n
u
p
o
f
H2
O2
i
n
p
la
n
t
ce
lls
.
I
n
th
is
ca
s
e
th
e
p
o
l
y
p
h
e
n
o
lic
co
m
p
o
u
n
d
h
a
s
a
h
i
g
h
a
n
tio
x
id
a
n
t
p
o
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tial,
p
r
o
v
id
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p
r
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tectio
n
ag
ai
n
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t
ca
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ce
r
b
y
in
h
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g
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x
id
ati
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d
a
m
a
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w
h
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is
k
n
o
w
n
as
a
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tial
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s
e
o
f
m
u
tatio
n
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Fre
e
r
ad
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ca
u
s
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o
x
id
ativ
e
d
am
a
g
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to
l
ip
id
s
,
p
r
o
tein
s
,
a
n
d
n
u
cleic
ac
id
s
[3
6
]
.
P
o
ly
p
h
e
n
o
l
an
t
io
x
id
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t
p
r
o
p
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n
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ac
it
y
o
f
s
ca
v
e
n
g
i
n
g
f
r
e
e
r
ad
icals
[
3
7
]
-
[3
9
].
3
.
3
.
SG
P
T
R
es
u
lts
o
f
m
ea
s
u
r
e
m
en
t
s
o
f
t
h
e
SGP
T
av
er
ag
e
o
f
th
e
liv
e
r
in
ea
ch
s
tu
d
y
g
r
o
u
p
ar
e
p
r
esen
ted
i
n
T
ab
le
4
.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
SS
N
:
2
2
5
2
-
8806
I
J
P
HS
Vo
l.
5
,
No
.
3
,
Sep
tem
b
er
201
6
:
2
8
4
–
2
9
3
290
T
ab
le
4
.
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h
e
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A
v
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ag
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i
n
R
at
s
Ser
u
m
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ac
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Gr
o
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p
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e
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me
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x
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5
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2
K2
4
7
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8
3
±
8
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6
6
3
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8
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5
0
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1
1
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4
7
4
P4
4
9
.
3
3
±
6
.
6
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5
P5
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0
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5
0
±
5
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4
3
6
P6
5
6
.
8
3
±
6
.
0
5
T
h
e
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ig
n
i
f
ica
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ce
le
v
el
(
α
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o
f
Kr
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s
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al
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ati
v
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te
s
t
is
0
.
1
8
9
(
α
>
0
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0
5
)
.
T
h
e
co
m
p
lete
r
es
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lts
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f
SG
PT
m
ea
s
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r
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m
e
n
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e
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Fig
u
r
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3
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u
r
e
3
.
R
esu
lts
o
f
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T
m
e
asu
r
e
m
en
t a
n
d
th
e
a
v
er
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r
ats s
er
u
m
B
ased
o
n
th
e
r
esear
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h
r
es
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lts
,
AL
T
lev
el
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n
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lo
o
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er
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m
o
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t
d
if
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er
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g
n
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ican
tl
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α
>
0
.
0
5
)
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T
h
is
in
d
icate
s
t
h
at
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er
th
at
h
ad
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ee
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u
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d
w
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h
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ax
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o
r
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d
ay
s
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id
n
o
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ig
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Ho
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U/L
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e
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ai
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ay
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n
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ll
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ats
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ill
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al
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ale
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at
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5
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5
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w
h
i
le
i
n
f
e
m
ales r
ats 2
5
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5
0
U/
L
[
2
4
]
.
SGP
T
(
AL
T
o
r
alan
in
e
a
m
i
n
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tr
an
s
f
er
ase)
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n
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z
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m
e
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tal
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t
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tr
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to
f
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r
m
o
x
alo
ac
etate
li
v
er
m
etab
o
lite
[
4
0
]
.
T
h
is
en
z
y
m
e
co
n
s
is
ts
o
f
4
9
6
a
m
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n
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ted
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n
g
th
e
ar
m
o
f
c
h
r
o
m
o
s
o
m
e
8
[4
1
]
,
[
4
2
]
.
T
h
u
s
,
i
n
t
h
e
ca
s
e
o
f
h
ep
ato
ce
ll
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lar
i
n
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r
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r
d
ea
t
h
,
t
h
e
r
elea
s
e
o
f
AL
T
f
r
o
m
d
a
m
a
g
e
d
liv
er
ce
lls
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s
i
n
cr
ea
s
i
n
g
b
y
m
ea
s
u
r
i
n
g
AL
T
ac
tiv
i
t
y
i
n
b
l
o
o
d
s
er
u
m
.
A
L
T
,
c
y
to
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n
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y
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e,
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s
f
o
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n
d
in
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g
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e
s
t
co
n
ce
n
tr
atio
n
s
i
n
t
h
e
liv
er
a
n
d
m
o
r
e
s
p
ec
i
f
icall
y
t
o
th
e
li
v
er
[4
3
]
.
I
n
ad
d
itio
n
to
th
e
liv
er
,
it is
al
s
o
f
o
u
n
d
in
k
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y
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d
,
in
s
m
alle
r
am
o
u
n
ts
,
in
s
k
e
letal
m
u
s
cle
ce
lls
[
4
4
]
.
T
h
e
ten
d
en
c
y
o
f
s
tab
ili
t
y
a
n
d
s
lig
h
tl
y
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ec
r
ea
s
ed
AL
T
lev
el
in
r
ats
b
lo
o
d
s
er
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m
i
s
s
u
s
p
ec
te
d
to
r
esu
lt
f
r
o
m
t
h
e
r
o
le
o
f
MP
E
p
o
l
y
p
h
en
o
ls
as
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tio
x
id
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t
s
o
r
f
r
ee
r
ad
icals
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ca
v
en
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h
at
p
r
ev
e
n
t
o
x
id
ativ
e
s
tr
ess
in
r
ats liv
er
,
w
h
ich
w
i
ll
m
a
y
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es
u
lt liv
er
n
ec
r
o
s
i
s
.
Asi
d
e
f
r
o
m
li
v
er
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is
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s
e
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d
d
am
a
g
e,
AL
T
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er
u
m
ac
ti
v
it
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n
b
e
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l
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ce
d
b
y
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n
u
m
b
e
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f
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to
r
s
u
n
r
elate
d
to
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v
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ec
r
o
s
i
s
[4
4
]
.
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h
er
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o
r
e,
th
e
v
ar
iab
ilit
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o
f
AL
T
lev
el
s
i
s
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g
ed
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y
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n
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y
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t c
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ld
n
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t b
e
p
r
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i
cted
in
th
i
s
s
t
u
d
y
.
4.
CO
NCLU
SI
O
N
AND
SU
G
G
E
S
T
I
O
N
R
es
u
lts
r
e
v
ea
led
th
at
u
p
to
d
a
y
1
6
SGOT
w
a
s
d
ec
r
ea
s
in
g
(
α
<
0
.
0
5
)
,
w
h
i
le
SGP
T
lev
els
w
a
s
s
tab
l
e
(
α
>
0
.
0
5
)
,
s
o
w
a
s
th
e
w
ei
g
h
t
o
f
th
e
liv
er
(
α
>
0
.
0
5
)
.
T
h
e
h
ig
h
e
s
t
av
er
a
g
e
w
e
ig
h
t
o
f
t
h
e
o
r
g
an
,
SGOT
an
d
SGP
T
w
as
i
n
p
o
s
iti
v
e
co
n
tr
o
l
g
r
o
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p
.
I
n
tr
ea
t
m
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n
t
g
r
o
u
p
,
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h
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w
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t
w
as
i
n
g
r
o
u
p
o
f
2
0
0
m
g
/
k
g
(
f
o
r
o
r
g
an
Evaluation Warning : The document was created with Spire.PDF for Python.
I
J
P
HS
I
SS
N:
2252
-
8806
Hep
a
to
p
r
o
tective
E
ffect
o
f Ma
n
g
o
s
teen
P
ee
l E
xtra
ct
o
n
B
o
r
a
x
-
I
n
d
u
ce
d
Ma
le
R
a
ts
(
Yu
n
ita
S
a
tya
P
r
a
tiw
i)
291
w
ei
g
h
ts
a
n
d
S
GP
T
)
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d
a
g
r
o
u
p
o
f
4
0
0
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g
/k
g
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n
S
GOT
)
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h
u
s
,
u
n
ti
l
d
a
y
1
6
MP
E
w
a
s
g
e
n
er
all
y
ab
le
to
p
r
o
v
id
e
h
ep
ato
p
r
o
tectiv
e
ef
f
e
cts,
m
ai
n
l
y
b
ased
o
n
SGOT
v
ar
iab
le
in
d
o
s
es
2
0
0
an
d
4
0
0
m
g
/k
g
.
I
t
h
as
b
ee
n
p
r
o
v
ed
th
at
liv
er
f
u
n
ctio
n
o
f
t
h
e
ex
p
er
i
m
en
ta
l
r
ats
w
as
s
till
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elativ
el
y
n
o
r
m
al.
T
h
is
h
ap
p
e
n
s
b
ec
au
s
e
t
h
er
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is
th
e
r
o
le
o
f
p
o
l
y
p
h
en
o
l
s
MP
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in
p
r
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tectin
g
f
r
o
m
ce
llu
lar
s
w
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n
g
t
h
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co
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ld
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n
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cr
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li
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n
d
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p
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o
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AD
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d
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tio
x
id
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t
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w
h
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m
a
y
p
r
o
tect
f
r
o
m
r
is
in
g
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h
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lev
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o
f
SGOT
an
d
SGP
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d
u
e
to
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ec
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o
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f
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o
m
o
x
id
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tr
ess
a
f
t
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o
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ax
in
d
u
ctio
n
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T
h
e
u
s
e
o
f
m
an
g
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tee
n
p
ee
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ex
tr
ac
t
s
h
o
u
ld
b
e
i
m
p
r
o
v
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as
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tio
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id
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t
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u
p
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t
s
.
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n
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itio
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f
u
r
t
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t
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ies
s
h
o
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ld
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e
ca
r
r
i
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t
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s
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a
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o
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f
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ad
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ACK
NO
WL
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D
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P
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f
.
R
.
B
a
m
b
an
g
W
ir
j
atm
ad
i,
d
r
,
M.
S.,
M.
C
N.
,
P
h
.
D
,
Sp
.
GK
,
P
r
o
f
.
Ma
n
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Ag
il,
M.
S.,
A
p
t.
,
a
n
d
Dr
.
M
er
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y
a
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a
A
d
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ian
i,
S.KM
.
,
M.
Kes
,
m
y
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ch
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u
p
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s
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f
o
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atie
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n
t
h
u
s
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co
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e
s
o
f
t
h
is
r
esear
ch
w
o
r
k
.
I
w
o
u
ld
a
ls
o
li
k
e
to
th
a
n
k
to
P
r
o
f
.
I
Ketu
t
Su
d
ian
a,
Dr
s
.
,
M.
Si.
f
o
r
h
is
ad
v
ice
an
d
as
s
is
tan
ce
in
k
ee
p
in
g
m
y
p
r
o
g
r
ess
o
n
s
c
h
ed
u
le.
M
y
g
r
atef
u
l
t
h
a
n
k
s
ar
e
al
s
o
e
x
ten
d
ed
to
Mr
s
.
E
v
i
A
r
f
ia
n
ti,
S.
KM
.
,
M.
Kes.,
Mr
.
Su
j
ar
w
o
,
Mr
.
Her
i
a
n
d
Mr
s
E
n
d
ah
f
o
r
th
e
ir
h
elp
i
n
d
o
in
g
at
t
h
e
lab
o
r
ato
r
y
p
h
ar
m
ac
y
a
n
d
b
io
ch
e
m
ical
.
Fin
all
y
,
I
w
i
s
h
to
th
a
n
k
m
y
h
u
s
b
a
n
d
,
m
y
p
ar
en
t
s
,
d
au
g
h
ter
,
s
i
s
ter
,
b
r
o
th
er
f
o
r
th
eir
s
u
p
p
o
r
t
an
d
en
co
u
r
ag
e
m
e
n
t t
h
r
o
u
g
h
o
u
t
m
y
s
tu
d
y
.
RE
F
E
R
E
NC
E
S
[1
]
Na
ti
o
n
a
l
A
g
e
n
c
y
o
f
Dru
g
a
n
d
F
o
o
d
o
f
th
e
Re
p
u
b
li
c
o
f
In
d
o
n
e
sia
,
―
P
e
rf
o
rm
a
n
c
e
Re
p
o
rts
o
f
F
o
o
d
a
n
d
Dru
g
A
d
m
in
istratio
n
o
f
th
e
Re
p
u
b
li
c
o
f
In
d
o
n
e
sia
t
h
e
f
irst
se
m
e
ste
r
o
f
2
0
1
2
,‖
Ja
k
a
rta
,
NA
DF
RI
,
2
0
1
2
.
[2
]
M
.
A
.
Do
u
rso
n
,
B.
M
a
ier,
F.
M
e
e
k
,
R.
Ba
r
e
il
le,
Ba
q
u
e
y
,
―
Bo
ro
n
T
o
lera
b
le
In
tak
e
R
e
-
e
v
a
lu
a
ti
o
n
o
f
T
o
x
ico
k
in
e
ti
c
s
f
o
r
D
a
ta De
riv
e
d
Un
c
e
rtain
ty
F
a
c
to
rs
,‖
Bi
o
l.
T
r
a
c
e
El
e
m.
Res
,
v
o
l/
i
ss
u
e
:
6
6
(
1
-
3)
,
p
p
.
4
5
3
-
4
6
3
,
2
0
0
3
.
[3
]
C.
L
e
w
is,
―
T
h
e
"
P
o
isi
o
n
S
q
u
a
d
"
a
n
d
t
h
e
A
d
v
e
n
t
o
f
F
o
o
d
a
n
d
Dru
g
s
Re
g
u
latio
n
,‖
USA
,
F
DA
Co
n
su
m
e
r
M
a
g
a
z
in
e
,
2
0
0
2
.
[4
]
A
.
P
u
sp
a
d
e
w
i,
―
G
i
v
in
g
o
f
Or
a
l
A
lp
h
a
L
ip
o
ic
Ac
id
(ALA
)
c
a
n
lo
w
e
r
lev
e
ls
o
f
m
a
lo
n
d
iald
e
h
y
d
e
(
M
DA
)
o
f
Blo
o
d
W
istar rats (Ra
tt
u
s
n
o
rv
e
g
icu
s) In
d
u
c
e
d
Ora
l
B
o
ra
x
,
‖
Po
stg
ra
d
u
a
te
T
h
e
sis
,
De
n
p
a
sa
r
,
Ud
a
y
a
n
a
Un
iv
e
rsit
y
,
2
0
1
2
.
[5
]
S.
S
e
ti
a
ti
,
―
F
re
e
ra
d
ica
ls,
a
n
ti
o
x
id
a
n
ts
a
n
d
a
g
in
g
p
ro
c
e
ss
,‖
M
e
d
ika
ma
g
a
zi
n
e
,
v
o
l/
iss
u
e
:
6
(
1
9
),
p
p
.
3
6
6
-
3
6
8
,
2
0
0
3
.
[6
]
W
.
J.
De
a
l,
―
M
e
tab
o
li
c
c
o
n
tro
l
a
n
d
stru
c
tu
re
o
f
g
l
y
c
o
l
y
ti
c
e
n
z
y
m
e
s
IV
.
Nic
o
ti
n
a
m
id
e
-
a
d
e
n
in
e
d
in
u
c
leo
t
id
e
d
e
p
e
n
d
e
n
t
in
v
it
r
o
re
v
e
rsa
l
o
f
d
isso
c
iatio
n
a
n
d
p
o
ss
i
b
le
in
v
iv
o
c
o
n
tr
o
l
o
f
y
e
a
st
g
l
y
c
e
ra
ld
e
h
y
d
e
3
-
p
h
o
sp
h
a
te
d
e
h
y
d
ro
g
e
n
a
se
s
y
n
th
e
sis
,‖
Bi
o
c
h
e
mistry
,
v
o
l.
8
,
p
p
.
2
7
9
5
–
2
8
0
5
,
1
9
6
9
.
[7
]
F
.
A
.
Be
tt
e
lh
e
i
m
,
W
.
H.
Bro
w
n
,
M
.
K.
Ca
m
p
b
e
ll
,
S
.
O.
F
a
rre
ll
,
―
In
tro
d
u
c
ti
o
n
to
G
e
n
e
ra
l
,
Org
a
n
ic,
a
nd
Bio
c
h
e
m
istr
y
,
Ei
g
h
th
Ed
i
ti
o
n
,‖
K
e
n
tu
c
k
y
,
T
h
o
m
so
n
Hig
h
e
r
Ed
u
c
a
t
io
n
,
2
0
0
7
.
[8
]
H.
T
u
rk
e
z
,
F.
G
e
y
ik
o
g
lu
,
A
.
T
a
t
a
r,
M
.
Ke
les
,
I.
Ka
p
lan
,
―
T
h
e
e
ffe
c
ts
o
f
S
o
m
e
Bo
ro
n
C
o
m
p
o
u
n
d
s
a
g
a
in
st
He
a
v
y
M
e
tal
T
o
x
icit
y
in
Hu
m
a
n
Blo
o
d
,‖
Exp
T
o
x
ico
l
P
a
th
o
l
,
v
o
l/
issu
e
:
6
4
(1
-
2)
,
p
p
.
93
-
1
0
1
,
2
0
1
2
.
[9
]
S
.
A
.
S
m
it
h
,
―
T
h
e
p
re
m
a
ire all
n
a
ti
o
n
a
l
li
v
e
r/
k
id
n
e
y
d
e
to
x
,‖
T
h
e
li
v
e
tree
,
A
lab
a
m
a
US
A
,
pp.
1
42
,
2
0
0
3
.
[1
0
]
M.
P
l
o
tk
e
n
,
―
De
to
x
if
ica
ti
o
n
a
n
d
d
ra
i
n
a
g
e
,
‖
2
0
0
7
.
D
ip
e
ti
k
9
M
e
i
2
0
1
6
,
d
a
ri
h
tt
p
:/
/w
ww
.
h
e
e
lu
sa
.
c
o
m
/
f
il
e
/
m
ic
e
/p
lo
tk
e
n
-
d
e
t
o
x
.
o
c
to
b
e
r.
n
o
2
9
/p
d
f
.
[1
1
]
P.
Oc
tav
ia,
―
Eff
e
c
t
o
f
Bo
ra
x
a
g
a
in
st
L
iv
e
r
Histo
p
a
th
o
l
o
g
y
Ov
e
r
v
ie
w
o
f
R
a
ts
(Ra
tt
u
s
n
o
rv
e
g
icu
s)
,‖
S
u
ra
b
a
y
a
,
F
a
c
u
lt
y
o
f
V
e
terin
a
r
y
M
e
d
icin
e
,
Un
iv
e
rsit
y
o
f
A
irl
a
n
g
g
a
,
2
0
1
2
.
[1
2
]
R.
S
h
u
k
la,
S
.
J.
S
u
ra
n
a
,
A
.
U.
T
a
t
iy
a
,
S
.
K.
Da
s,
―
In
v
e
stig
a
ti
o
n
o
f
h
e
p
a
to
p
r
o
tec
ti
v
e
e
ff
e
c
ts
o
f
p
ip
e
rin
e
a
n
d
sily
m
a
rin
o
n
D
-
g
a
lac
to
sa
m
in
e
in
d
u
c
e
d
h
e
p
a
to
to
x
ic
it
y
in
ra
ts
,‖
Res
e
a
rc
h
J
o
u
r
n
a
l
o
f
Ph
a
rm
a
c
e
u
ti
c
a
l,
B
io
l
o
g
ic
a
l
a
n
d
C
h
e
mic
a
l
S
c
ien
c
e
s
,
v
o
l/
issu
e
:
2
(3
)
,
p
p
.
9
7
5
-
982
,
2
0
1
1
.
[1
3
]
J.
M
.
P
e
ters
,
E.
M
.
Bo
y
d
,
―
Org
a
n
w
e
i
g
h
ts
a
n
d
w
a
ter
le
v
e
ls
o
f
t
h
e
ra
t
f
o
ll
o
w
in
g
re
d
u
c
e
d
f
o
o
d
i
n
tak
e
,‖
J
Nu
tr
,
v
o
l/
issu
e
:
9
0
(4
)
,
p
p
.
3
5
4
–
6
0
,
1
9
6
6
.
[1
4
]
C.
J.
P
f
e
iffer,
―
A
m
a
th
e
m
a
ti
c
a
l
e
v
a
lu
a
ti
o
n
o
f
th
e
th
y
m
ic
w
e
ig
h
t
p
a
ra
m
e
ter
,‖
T
o
x
ico
l
Ap
p
l
Ph
a
rm
a
c
o
l
,
v
o
l/
issu
e
:
1
3
(
2
)
,
p
p
.
2
2
0
–
2
2
7
,
1
9
6
8
.
[1
5
]
H.
A
.
Ju
n
g
,
B
.
N
.
S
u
,
W
.
J.
K
e
ll
e
r,
A
.
D
.
Kin
g
h
o
rn
,
―
A
n
ti
o
x
ii
d
a
n
t
X
a
n
t
h
o
n
e
s
F
ro
m
T
h
e
P
e
rica
r
p
Of
G
a
rc
ian
a
M
a
n
g
o
sta
n
a
(M
a
n
g
o
tee
n
)
,‖
J
o
u
rn
a
l
o
f
Ag
ric
u
lt
u
r
a
l
a
n
d
F
o
o
d
Ch
e
mistry
,
v
o
l.
54
,
p
p
.
2
0
7
7
–
2
0
8
2
,
2
0
0
6
.
[1
6
]
A
.
Zar
e
n
a
,
K.
U.
S
a
n
k
a
r,
―
P
h
e
n
o
li
c
A
c
id
,
F
lav
o
n
o
id
P
r
o
f
il
e
a
n
d
A
n
ti
o
x
id
a
n
t
A
c
ti
v
it
y
in
M
a
n
g
o
ste
e
n
(
Ga
rc
in
ia
ma
n
g
o
sta
n
a
L
.
)
P
e
r
ica
rp
,‖
J
o
u
r
n
a
l
Fo
o
d
Bi
o
c
h
e
mistr
y
,
v
o
l/
issu
e
:
3
6
(5
)
,
p
p
.
6
2
7
-
6
3
3
,
2
0
1
2
.
[1
7
]
Y.
I.
M
iry
a
n
ti
,
S.
L
a
n
n
y
,
B.
Ku
rn
iaw
a
n
,
I.
S
tep
h
e
n
,
―
A
n
ti
o
x
id
a
n
ts
Ex
trac
ti
o
n
f
ro
m
M
a
n
g
o
ste
e
n
P
e
e
l
(G
a
rc
in
ia
m
a
n
g
o
sta
n
a
L
in
n
.
)
,‖
Ba
n
d
u
n
g
,
Re
se
a
rc
h
Re
p
o
rt,
In
stit
u
te
f
o
r
Re
se
a
rc
h
a
n
d
Co
m
m
u
n
it
y
S
e
r
v
ice
s,
P
a
ra
h
y
a
n
g
a
n
Ca
t
h
o
li
c
Un
iv
e
rsit
y
,
2
0
1
1
.
[1
8
]
D.
M
.
Bo
e
ste
n
,
S
.
N.
U
n
g
e
rn
-
S
t
e
rn
b
e
rg
,
G
.
J.
Ha
rto
g
,
A.
Ba
st,
―
P
r
o
tec
ti
v
e
P
lei
o
tro
p
ic
Ef
f
e
c
t
o
f
F
lav
o
n
o
i
d
s
o
n
NA
D+
Lev
e
ls
in
En
d
o
t
h
e
li
a
l
Ce
ll
s
Ex
p
o
s
e
d
t
o
Hig
h
G
lu
c
o
se
,‖
Ox
id
a
ti
v
e
M
e
d
icin
e
a
n
d
Ce
ll
u
lar
L
o
n
g
e
v
it
y
,
p
p
.
1
–
7
,
2
0
1
4
.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
SS
N
:
2
2
5
2
-
8806
I
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P
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Vo
l.
5
,
No
.
3
,
Sep
tem
b
er
201
6
:
2
8
4
–
2
9
3
292
[1
9
]
C.
Esc
a
n
d
e
,
V.
Ni
n
,
N.
L
.
P
rice
,
V.
Ca
p
e
ll
i
n
i,
A
.
P
.
G
o
m
e
s,
M
.
T
.
Ba
rb
o
sa
,
e
t
a
l
.
,
―
F
lav
o
n
o
i
d
A
p
ig
e
n
in
Is
a
n
In
h
i
b
it
o
r
o
f
T
h
e
NA
D+
a
se
CD3
8
:
Im
p
li
c
a
ti
o
n
s
f
o
r
Ce
ll
u
lar
NA
D+
M
e
tab
o
li
sm
,
P
ro
tei
n
A
c
e
t
y
latio
n
,
a
n
d
T
re
a
tme
n
t
o
f
M
e
tab
o
li
c
S
y
n
d
ro
m
e
,‖
Dia
b
e
tes
,
v
ol
.
62
,
p
p
.
1
0
8
4
–
1
0
9
3
,
2
0
1
3
.
[2
0
]
D.
F
ly
n
n
,
―
S
tu
d
e
n
t
G
u
id
e
to
S
P
S
S
,
‖
Ne
w
Yo
rk
,
Ba
rn
a
rd
Co
ll
e
g
e
,
De
p
a
rtme
n
t
o
f
Bio
lo
g
ica
l
S
c
ien
c
e
s
,
2
0
0
8
.
[2
1
]
A
.
H.
S
c
h
a
p
ira,
―
In
b
o
rn
a
n
d
i
n
d
u
c
e
d
d
e
f
e
c
ts
o
f
m
it
o
c
h
o
n
d
ria
,‖
Ar.
Ne
u
ro
l
,
v
o
l.
55
,
p
p
.
1
2
9
3
-
1
2
9
6
,
1
9
9
8
.
DO
I
:
1
0
.
1
0
0
1
/arc
h
n
e
u
r.
5
5
.
1
0
.
1
2
9
3
.
[2
2
]
S
.
L
.
Ro
b
b
in
s,
―
Ce
ll
u
lar
a
d
a
p
tatio
n
,
c
e
ll
in
j
u
ry
,
a
n
d
c
e
ll
d
e
a
th
,‖
in
A
.
A
.
In
:
Ku
m
a
r
V
.
,
―
Ro
b
b
i
n
s
a
n
d
Co
tran
P
a
t
h
o
l
o
g
ic Ba
sis o
f
Dise
a
se
7
th
,‖
p
p
.
1
6
-
1
8
,
3
2
4
,
Ch
in
a
,
El
se
v
ier.
In
c
,
2
0
0
5
.
[2
3
]
S
.
A
.
Ba
il
e
y
,
R.
H.
Zi
d
e
ll
,
R.
W
.
P
e
rry
,
―
Re
latio
n
sh
i
p
s
Be
tw
e
e
n
Org
a
n
W
e
ig
h
t
a
n
d
Bo
d
y
/
Bra
in
W
e
ig
h
t
in
t
h
e
Ra
t
:
W
h
a
t
Is t
h
e
Be
st A
n
a
l
y
ti
c
a
l
En
d
p
o
in
t?
,‖
T
o
x
ico
l
o
g
ic
Pa
t
h
o
l
o
g
y
,
v
o
l.
32
,
p
p
.
4
4
8
–
4
6
6
,
2
0
0
4
.
[2
4
]
R.
L
.
Ha
ll
,
―
Cli
n
ica
l
P
a
th
o
l
o
g
y
o
f
L
a
b
o
ra
to
ry
A
n
i
m
a
ls,
‖
in
Ga
d
,
S
.
C.
,
(Ed
s),
―
A
n
im
a
l
M
o
d
e
ls
in
T
o
x
o
c
o
lo
g
y
,
‖
S
e
c
o
n
d
Ed
it
io
n
,
Ne
w
Yo
rk
,
T
a
y
l
o
r
a
n
d
F
ra
n
k
G
ro
u
p
,
2
0
0
7
.
[2
5
]
S
.
F
.
F
ried
m
a
n
,
P.
M
a
rti
n
,
J.
S
.
M
u
n
o
z
,
―
L
a
b
o
ra
to
ry
e
v
a
lu
a
ti
o
n
o
f
th
e
p
a
ti
e
n
t
w
it
h
li
v
e
r
d
ise
a
s
e
,‖
i
n
―
H
e
p
a
to
lo
g
y
,
a
tex
tb
o
o
k
o
f
li
v
e
r
d
ise
a
se
,‖
pp.
1,
661
-
7
0
9
,
P
h
i
led
e
lp
h
ia
,
S
a
u
n
d
e
rs p
u
b
li
c
a
ti
o
n
,
2
0
0
3
.
[2
6
]
H.
R.
Ro
se
n
,
E.
B.
Ke
e
f
e
,
―
Ev
a
lu
a
ti
o
n
o
f
a
b
n
o
rm
a
l
li
v
e
r
e
n
z
y
m
e
s,
u
se
o
f
li
v
e
r
tes
ts
a
n
d
th
e
se
r
o
lo
g
y
o
f
v
iral
h
e
p
a
ti
ti
s
,‖
i
n
―
L
iv
e
r
d
ise
a
se
,
d
i
a
g
n
o
sis
a
n
d
m
a
n
a
g
e
m
e
n
t
1
st
e
d
,‖
p
p
.
24
-
35
,
Ne
w
Yo
rk
,
Ch
u
rc
h
il
l
li
v
in
g
sto
n
e
p
u
b
li
sh
e
rs
,
2
0
0
0
.
[2
7
]
M
.
A
.
As
ti
n
in
g
ru
m
,
―
Eff
e
c
t
o
f
b
o
ra
x
to
li
v
e
r
d
a
m
a
g
e
o
f
s
w
is
s
w
e
b
ste
r
stra
in
o
f
m
a
le
m
ic
e
,
e
x
p
e
ri
m
e
n
tal
stu
d
ies
b
y
S
G
P
T
a
n
d
S
G
OT
m
e
a
su
re
m
e
n
t
,‖
S
e
m
a
ra
n
g
,
F
a
c
u
lt
y
o
f
M
e
d
icin
e
,
Un
iv
e
rsit
y
o
f
Dip
o
n
e
g
o
ro
,
2
0
1
1
.
[2
8
]
S.
S
h
e
rlo
c
k
,
―
A
ss
e
ss
m
e
n
t
o
f
li
v
e
r
f
u
n
c
ti
o
n
Dise
a
se
o
f
li
v
e
r
a
n
d
b
il
i
a
r
y
s
y
ste
m
,‖
in
S
.
S
h
e
rlo
c
k
,
1
0
t
h
e
d
n
,
p
p
.
17
-
32
,
L
o
n
d
o
n
,
Blac
k
w
e
ll
sc
ien
c
e
lt
d
,
1
9
9
7
.
[2
9
]
R.
M
.
G
re
e
n
,
S
.
F
lam
m
,
―
AG
A
t
e
c
h
in
a
l
re
v
iew
o
f
e
v
a
l
u
a
ti
o
n
o
f
li
v
e
r
c
h
e
m
istr
y
te
sts,‖
Ga
stro
e
n
ter
o
lo
g
y
,
v
o
l.
1
2
3
,
pp.
1
3
6
7
-
1
3
8
4
,
2
0
0
2
.
[3
0
]
T
.
R.
Bo
y
d
e
,
A
.
L
.
L
a
tn
e
r,
―
S
tarc
h
g
e
l
e
lec
tro
p
h
o
re
sis
o
f
tran
sa
m
in
a
se
s
in
h
u
m
a
n
ti
ss
u
e
s
e
x
trac
ts
a
n
d
se
ru
m
,‖
Bi
o
c
h
e
m J
,
v
o
l.
82
,
p
p
.
52
-
57
,
1
9
6
1
.
[3
1
]
Y.
S
a
k
a
g
ish
i,
―
A
lan
in
e
a
m
in
o
tran
sf
e
ra
s
e
(
A
LT
)
,‖
Nip
p
o
n
Ri
n
,
in
M
c
Do
n
a
ld
,
G
.
B.
,
T
iru
m
a
li
,
N.
,
―
In
tes
ti
n
a
l
a
n
d
li
v
e
r
to
x
ic
,‖
sh
o
,
v
o
l
.
5
3
,
p
p
.
1
1
4
6
–
1
1
5
0
,
1
9
9
5
.
[3
2
]
R.
Re
j,
―
Am
in
o
tran
sf
e
ra
se
s
in
d
is
e
a
se
,‖
Dia
g
n
.
E
n
zy
mo
l,
v
o
l.
9
,
i
n
L
e
Clu
y
se
,
E.
L
.
,
A
u
d
u
s,
K.
L
.
,
a
n
d
Ho
c
h
m
a
n
,
J.
H.
,
Fo
rm
a
ti
o
n
,
p
p
.
6
6
7
–
6
8
7
,
1
9
8
9
.
[3
3
]
N.
J.
P
a
p
p
a
s,
―
S
o
u
rc
e
o
f
in
c
re
a
se
d
se
ru
m
a
sp
a
rtate
a
n
d
a
lan
in
e
a
m
in
o
tra
n
sf
e
ra
s
e
:
C
y
c
lo
h
e
x
i
m
id
e
e
ff
e
c
t
o
n
c
a
rb
o
n
tetra
c
h
lo
ri
d
e
h
e
p
a
t
o
to
x
icity
,‖
Cli
n
.
Ch
im.
Act
a
,
v
o
l.
1
5
4
,
p
p
.
1
8
1
–
190
,
1
9
8
6
.
[3
4
]
B.
Na
lp
u
s,
A.
V
a
ss
a
u
lt
,
S.
Ch
a
rp
i
n
,
e
t
a
l.
,
―
S
e
ru
m
m
it
o
c
h
o
n
d
rial
a
sp
a
rtate
a
m
o
n
it
ra
n
sf
e
ra
s
e
a
s
a
m
a
rk
e
r
o
f
c
h
ro
n
ic
a
lco
h
o
li
sm
d
iag
n
o
stic v
a
lu
e
a
n
d
i
n
terp
re
tati
o
n
i
n
a
li
v
e
r
u
n
it
,‖
He
p
a
to
l
o
g
y
,
v
o
l.
6
,
p
p
.
6
0
8
-
6
1
3
,
1
9
8
6
.
[3
5
]
A
.
F
.
G
.
S
late
r,
C.
S
tef
a
n
,
I.
No
b
e
l,
D.
V.
Do
b
b
e
lstee
n
,
S.
Orre
n
i
u
s,
―
S
ig
n
a
li
n
g
m
e
c
h
a
n
is
m
s
a
n
d
o
x
id
a
ti
v
e
stre
ss
in
a
p
o
p
t
o
sis
,‖
T
o
x
ico
lo
g
y
L
e
tt
e
rs
,
v
o
l.
8
2
,
p
p
.
1
4
9
–
1
5
3
,
1
9
9
5
.
[3
6
]
G
.
H.
S
h
u
i,
L
.
P
.
L
e
o
n
g
,
―
A
n
a
l
y
s
is
o
f
p
o
l
y
p
h
e
n
o
li
c
a
n
ti
o
x
id
a
n
ts
in
sta
r
f
ru
it
u
sin
g
li
q
u
id
c
h
r
o
m
a
to
g
r
a
p
h
y
a
n
d
m
a
ss
sp
e
c
tro
m
e
tr
y
,‖
J
Ch
ro
ma
to
g
r A
,
v
o
l.
1
0
2
2
,
p
p
.
67
-
75
,
2
0
0
4
.
[3
7
]
B.
Ya
n
g
,
A.
Ko
tan
i,
K.
A
r
a
i,
F.
Ku
su
,
―
Esti
m
a
ti
o
n
o
f
th
e
a
n
ti
o
x
i
d
a
n
t
a
c
ti
v
it
ies
o
f
f
lav
o
n
o
id
s
f
ro
m
t
h
e
ir
o
x
id
a
ti
o
n
p
o
ten
ti
a
ls
,‖
An
a
l
S
c
i
,
v
o
l.
17
,
p
p
.
599
-
6
0
4
,
2
0
0
1
.
[3
8
]
N.
Co
telle,
―
Ro
le o
f
f
lav
o
n
o
id
s i
n
o
x
id
a
ti
v
e
stre
ss
,‖
Cu
rr
T
o
p
M
e
d
Ch
e
m
,
v
o
l.
1
,
p
p
.
5
6
9
-
59
,
2
0
0
1
.
[3
9
]
R.
M
.
F
a
c
in
o
,
M.
Ca
rin
i,
L.
F
ra
n
z
o
i,
O.
P
iro
la,
E.
Bo
sisi
o
,
―
P
h
y
to
c
h
e
m
i
c
a
l
c
h
a
ra
c
teriz
a
ti
o
n
a
n
d
ra
d
ica
l
sc
a
v
e
n
g
e
r
a
c
ti
v
it
y
o
f
f
lav
o
n
o
id
s
f
ro
m
He
li
c
h
ry
su
m
it
a
li
c
u
m
G
.
Do
n
(Co
m
p
o
sitae
)
,‖
Ph
a
rm
a
c
o
l
Res
,
v
o
l.
22
,
p
p
.
7
0
9
-
7
2
1
,
1
9
9
0
.
[4
0
]
C.
P
rice
,
K.
A
lb
e
rti
,
―
Bio
c
h
e
m
ica
l
a
s
se
ss
m
e
n
t
o
f
li
v
e
r
f
u
n
c
ti
o
n
,‖
in
W
ri
g
h
t
R
e
t.
a
l.
,
e
d
s.
,
―
L
i
v
e
r
a
n
d
b
il
iary
d
ise
a
se
s
—
p
a
th
o
p
h
y
sio
lo
g
y
,
d
iag
n
o
sis,
m
a
n
a
g
e
m
e
n
t
,‖
pp
.
3
8
1
-
4
1
6
,
L
o
n
d
o
n
,
W
.
B.
S
a
u
n
d
e
rs
,
1
9
7
9
.
[4
1
]
M.
Ish
ig
u
r
o
,
K.
T
a
k
io
,
M.
S
u
z
u
k
i,
R.
Oy
a
m
a
,
T.
M
a
tsu
z
a
w
a
,
K.
Ti
tan
i,
―
Co
m
p
lete
a
m
in
o
a
c
id
se
q
u
e
n
c
e
o
f
h
u
m
a
n
li
v
e
r
c
y
to
so
li
c
a
lan
in
e
a
m
in
o
tran
s
f
e
r
a
se
sp
e
c
tral
m
e
th
o
d
s
,‖
Bio
c
h
e
mistry
,
v
o
l.
30
,
p
p
.
1
0
4
5
1
-
1
0
4
5
7
,
1
9
9
1
.
[4
2
]
M
.
M
.
S
o
h
o
c
k
i,
L
.
S
.
S
u
l
li
v
a
n
,
W
.
R.
Ha
rriso
n
,
E.
J.
S
o
d
e
rg
re
n
,
F
.
F
.
El
d
e
r,
G.
W
e
in
sto
c
k
,
e
t
a
l.
,
―
Hu
m
a
n
g
lu
tam
a
te
p
y
ru
v
a
te
tran
sa
m
in
a
s
e
(G
P
T
)
:
lo
c
a
li
z
a
ti
o
n
to
8
q
2
4
.
3
,
c
DN
A
a
n
d
g
e
n
o
m
ic
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ield
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iy
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o
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5
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.
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h
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2
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Un
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ra
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m
in
istratio
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lt
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li
c
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a
lt
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Ca
re
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g
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m
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t
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tere
st
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e
A
irl
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n
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g
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Un
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in
2
0
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4
.
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is
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lec
tu
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r
a
t
Je
m
b
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r
M
u
h
a
m
m
a
d
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a
h
Un
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rsity
.
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e
a
lso
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id
a
lo
t
o
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se
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rc
h
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c
iall
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n
u
rsin
g
f
ield
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d
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sp
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a
k
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t
so
m
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a
ti
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a
l
se
m
in
a
rs.
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o
m
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p
u
b
li
c
a
ti
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n
s
sc
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ti
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ic
w
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th
a
t
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s
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d
o
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b
y
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im
in
n
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ti
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l
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rn
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ls
.
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a
lso
d
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d
a
lo
t
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c
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m
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it
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rv
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lag
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m
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se
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s
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a
c
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s,
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e
m
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r
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a
m
m
a
d
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a
h
Un
iv
e
rsit
y
,
f
ro
m
2
0
0
7
to
2
0
1
1
.
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