COMPARATIVE STUDY BETWEEN ACUTE AND CHRONIC [601954]

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COMPARATIVE STUDY BETWEEN ACUTE AND CHRONIC
LIVER INJURIES; RELEV ANCE OF TUMOR NECROSIS FACTOR
SUPER FAMILY 14 AND TRANSFORMING GROWTH FACTOR β
RECEPTOR І
Elsayed Gomaa Elsayed Elsakka1*, Gamil Mohammed Abd -Allah1, Ahmed
Mohammed Ibrahim Mansour2, Ahmed Ibrahim Abulsoud1 and Sayed Abdel
Raheem3
1DEPARTMENT OF BIOCHEMISTRY , FACULTY OF PHARMACY , ALAZHAR UNIVERSITY ,
CAIRO , EGYPT . 2DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY , FACULTY OF
PHARMACY , ALAZHAR UNIVERSITY , CAIRO , EGYPT . 3DEPARTMENT OF PATHOLOG Y,
FACULTY OF MEDICINE , ALAZHAR UNIVERSITY , CAIRO , EGYPT .
ABSTRACT
The aim of this study is to explore the biochemical difference between acute and chronic
liver injuries regarding the expression pattern of tumor necrosis factor superfamily 14 and
transforming g rowth fa ctor β receptor І . For achievement of this aim, Four Sprague –
Dawley rat groups were used for the experiment; Control group, acute toxicity group,
fibrosis group and cirrhosis group.
On the day after the last dose, rats were anestheti zed with diethyl ether and blood samples
were collected for measurement of blood chemistry. The animals were then euthanized,
and tissue samples from the livers harvested and divided into 2 parts; one part was
processed for standard histology and immunoflu orescence techniques and the other was
homogenized for oxidative status assessment.
The major o bserv ations include upregulation of tumor necrosis factor superfamily 14 and
transforming growth factor β receptor І in chronic liver injury; while tumor n ecrosis
factor superfamily 14 was shown to upregulate in cirrhosis stage only; transforming
growth factor β receptor І was shown to upregulate at fibrosis and cirrhosis stages. Tumor
necrosis factor superfamily 14 was shown to locate mainly at the cytopla sm of the cells at
cirrhotic nodule border while transforming growth factor β receptor І localization was
shown to occur mainly at the cell membrane .
From our results we can conclude that tumor nec rosis factor superfamily 14 and
transforming growth factor β receptor І are of critical importance in pathogenesis of
chronic liver injury so they may be used as a target for chronic liver injury therapy and/or
candidate marker for diagnosis and/or prognosis of chronic liver injury.

Key Words: TNFSF14, TGFβRІ , liver injury.
*Correspondence author (e mail; [anonimizat])

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INTRODUCTION
Liver plays a great role in the preservation and body homeostasis regulation. It is
involved in most biochemical cascades to growth, protection against disease , nutrient
fund, energy facility and reproduction (Sharma et al., 1991) . Several etiological factors
can contribute to hepatotoxicity including therapeutic agents, natural chemicals,
laboratory and manufacturing agents and herbal therapies (Ostapowicz et a l., 2002) .
Carbon tetra chloride (CCl 4) is one of the most common models for inducing
hepatotoxicity. It is converted into a toxic CCl 3- radical by hepatic cytochrome P4502E1
(CYP2E1).Thus; it causes an acute Centro -lobular necrosis which starts a wound he aling
response (fibrosis) (Domenicali et al., 2009) .
Tumor necrosis factor superfamily 14 ( TNFSF14) is member in the TNF
superfamily that is involved in innate and adaptive immune responses as well as in
regulation of cell survival and proliferation (Grang er and Rickert, 2003) . It was
demonstrated to have a crucial role in fibrous proteins precipitation and fibrosis cascades
in different tissues (Granger and Rickert, 2003;Doherty et al., 2011;Yamamoto,
2006;Herro et al., 2015a) . Transforming growth factor β receptors (TGF -βRs) are of 2
types TGF -βRІ and TGF -βRІІ. They mediate hepatic stellate cell (HSC) activation
(Roberts, 1999) after binding to their ligand cytokine TGF -β, the profibrogenic cytokine
that traditionally have been considered the key fibrogenic stimulus to HSC (Tsukamoto,
1999) so the aim of this study was to explore the biochemical difference between acute
and chronic liver injuries regarding the expression pattern of TNFSF14 and TGFβRІ at
different stages of liver injury; an aspect of study that was verified by investigation of the
localization of these proteins in different stages of liver injury .

MATERIALS AND METHOD S
Animal model.
Adult male Sprague -Dawley rats weighing 250 –300 g were used in the
current study. The animals were purchased from the breeding colony maintained at the
animal house of the Nile Company for pharmaceuticals, Cairo, Egypt. They were housed
in the animal facility of Faculty of Pharmacy, Al -Azhar University in 20 × 18 × 25 cm
plastic cages with stainless ste el wire lids and mesh floor with 5 animals per cage. They
were kept at 23±1 °C, at 55 % relative humidity, with 12:12 -h light: dark cycle, and
maintained on a standard rodent chow (El -Nasr Company, Abou -Zaabal, Cairo, Egypt),
food and water ad libitum . Ani mals were randomly divided into four groups: control
group: 9 rats: received corn oil (2ml/kg/twice weekly/IP) ; acute toxicity group: 10 rats
were injected 50 % CCl 4 in corn oil (4 ml/kg/IP/single dose) (Fleurentin et al., 1986) ;
fibrosis group:12 rats were injected with 50 % CCl 4 in corn oil (4 ml/kg/IP/twice
weekly/6weeks) and finally cirrhosis group: 10 rats were injected with 50 % CCl 4 in corn
oil (4 ml/kg/IP/twice weekly/6 weeks) followed by 5 weeks of CCl 4 treatment with t he
half of the previous dose. On the day after the last dose, rats were anesthetized with
diethyl ether and blood samples were collected in suitable tubes for measurement of
blood chemistry and complete blood count (CBC) . The animals were then euthanized,
and tissue samples from the livers were harvested and di vided into 2 parts; one part was
processed by standard histology and immunofluorescence techniques and the other was

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homogenized in 0.15 M KCl for malondialdehyde (MDA ), reduced glutathione (GSH)
and superoxide dismutase (SOD ) assay. All animal procedures were performed in
accordance with the international guide for the care and use of laboratory animals
(Institute of Laboratory Animal Resources (US) et al., 1985)
Antibodies and chemicals.
Rabbit polyclonal TNFSF14 and TGFβRІ antibodies were purchased fro m
Santa Cruz Biotechnology (CA, USA). Cy3 -conjugated goat anti -rabbit antibody was
purchased from Jackson Immunoresearch (PA, USA). 4, 6 – Diamidino -2- phenyl indole
(DAPI) and CCl 4 were purchased from Sigma -Aldrich (MO, USA).
Biochemical analysis.
Serum enzymatic activities of transaminases (ALT and AST) were estimated by
kinetic method according to the method of international federation of clinical chemistry
(IFCC) (Bergmeyer et al., 1986) . Alkaline phosphatase (ALP) activity was assay
according to the m ethod of IFCC (Tietz et al., 1983) and serum albumin concentration
according to the method described by Gendler (Gendler, 1984) . The liver homogenate
was used for the determination of the oxidative stress parameters. The level of
thiobarbituric acid -reactive substances measured as MDA was determined as described
by Mihara and Uchiyama (Mihara and Uchiyama, 1978) while t he activity of SOD was
determined using the method described by Marklund (Marklund, 1985) and finally GSH
was determined according to method of Beutler and his team (Beutler et al., 1963) .
EDTA blood samples were used for CBC using Mindray® 2800 vet Autocounter (Shenzhen,
China ).
Immunofluorescence analysis.
Slides containing liver tissues sections were h andled according to method
described by Abdel -Bakky and his associates (Abdel -Bakky et al., 2011) . The primary
TNFSF14 and TGFβRІ antibodies were diluted in blocking solution in the suitable
dilution (1:400) and left overnight in 4 °C. Secondary antibody ( cyanine red conjugated)
diluted in the blocking solution was incubated for 30 min and the nuclei were
counterstained using DAPI. Finally, all slides were mounted with the fluoromount
solution, covered by covering slips, and allowed to stand for detection b y
immunofluorescence microscope (Leica DM 5500B).
Statistical analysis.
Data were presented as the mean ±SE. Statistical analysis was performed
using one -way analysis of variance (ANOVA) follow ed by Tukey -Kramer as a post test,
according to the number of groups. The 0.05 level of probability was used as the criterion
of significance using GraphPad Prism software version 5 (GraphPad Software Inc, CA,
USA).
RESULTS
Liver functions and oxidative status assessment.
To assess liver functions; we have performed liver function tests including
serum transaminases, ALP, and albumin. The oxidative status of liver tissues was
determined through M DA and SOD assay .

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As indicated in Table 1; Administration of I.P. CCl 4 significantly elevated
serum transaminases activities compared to control whatever the duration of
administration. While ALP activity showed significant elevation only in chronic liver
toxicity (fibrosis and cirrhosis) with minimal change in acute toxicity compared to control
group, Serum albumin concentration showed significant decrease only in cirrhosis
stage. On the other hand; hepatic MDA content was significa ntly increased in all stages
of liver injury compared to control group while SOD activity and GSH content showed
significant decreases in liver injuries .
Assessment of some selected blood parameters
Table 1 indicates that RBCs, Hb and platelets show significant decrease in
cirrhosis model while WBCs show significant increase in fibrosis model compared to
control group.
Expression and localization of TNFSF14.
Figure 1 A shows that TNFSF14 protein showed well defined expression
only in hepatic tissue that showed well de fined cirrhosis; while there no protein
expression in normal liver tissues, acute toxicity model and fibrosis stage. It wa s also
noted that the expression was located mainly in the cirrhotic nodule borders; area that
showed high density of fibroblasts while areas that showed parenchymal cells as interior
of the cirrhotic nodule didn’t show expression. It was noted that t he expression increased
by about 38% in 11weeks CCl 4 treated group compared to control group while there
weren’t significant expression change in other groups as indicated in figure 1 B
Expre ssion and localization of TGFβRІ .
Figure 2A shows that TGFβR1 protein exhibited minimal expression in liver
tissues of control group animals and also acute toxicity model . The expression was
increased on conversion of toxicity from acute to chronic with maximal expression in
fibrosis and cirrhosis groups. It was noted that the expression increased by about 146% in
fibrosis group and by 55 % in cirrhosis group as indicated in Figure 2B. Regarding
localization; it was observed that the expression is located in the cell membrane of
epithelial hepatic tissue. It was also noted that the expression occur red in areas that shows
maximal lesions as necrosis and steatosis. On the other hand; it appears as intense area
filling the cytoplasm extending along the fibrous septa and surrounding the cirrhotic
nodule in areas that show high density of fibroblastic cells as shown in 11 weeks group.
On the other hand there was also minimal expression inside the cirrhotic nodule.
Histopathological findings.
Effects of CCl 4 treatment on histopathological findings of liver tissue are
represented in Table 2 and Figure 3. The control group showed normal hepatic
architecture. On contrast, CCl 4 treated groups showed pathological findings changes
according to the duration of treatment.
Acute toxicity group show ed average portal tract (PT) (yellow arrow) without
interface activity or underlying fibrosis. On the other hand; it showed spotty necrosis
(black arrow), and mild micro -vesicular steatosis and dilated central vein. Fibrosis group
showed expanded PT with f ibrous septa extending from PT to PT (yellow arrows),

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marked micro – and macro -vesicular steatosis. The hepatocytes exhibited some aspects of
single cell necrosis with dilated central veins and mild interface activity.
Cirrhosis group showed markedly expa nded PT (yellow arrows) with definite
inflammatory infiltrate, complete nodular formation (definite cirrhosis) and marked
micro – and macro -vesicular steatosis. The hepatocytes exhibited single cell necrosis with
mild spotty necrosis. Finally; the central v eins were markedly dilated with marked
interface activity.
Table 1: Liver functions and oxidative status assessment tests.
Control Acute toxicity
group Fibrosis group Cirrhosis group
ALT (IU/L) 46.6±2.85 294±11.9(a)(b) 349±13.4(a) 298±8.48(a)
AST (IU/L) 54.1±2.65 419±11.0(a) 436±15.4(a) 368±13.4(a)(b)
ALP (IU/L) 312±21.9 395±11.1(b) 570±24.5(a) 790±24.9(a)(b)
Albumin (g/dl) 3.81±0.08 3.8±0.06(b) 3.39±0.13 2.69±0.07(a)
MDA (nmol/g
tissue) 4.73±0.318 23.7±2.35(a)(b) 31.9±1.44(a) 38.1±1.74(a)
SOD (U/mg tissue) 526±25.2 308±8.05(a)(b) 223±14(a) 171±6.57(a)
GSH
(mmol/gm.tissue) 2.01± 0.117 1.21± 0.0828(a) 1.41± 0.0588(a) 1.10± 0.0433(a)
RBCs (×106/mm2) 11.4±0.449 11±0.472 9.71±0.257 7.4±0.188(a)
WBCs (×103/mm2) 8.1±0.418 11.1±0.814(b) 18.8±1.75(a) 11.4±0.711(b)
Hb (Gm %) 18.3±1.11 17.8±0.781 15.6±0.396 12.7±0.573(a)
Platelets
(×103/mm2) 757±50.4 743±32.8 735±57.7 503±25.3(a)(b)

Data are expressed as mean ± SEM
(a) Significantly different from control group
(b) Significantly different from fibrosis group using one -way ANOVA followed by
Tukey -Kramer test for multiple comparison test at P≤0.05

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Table 2: Histopathological findings of the studied groups

control Acute toxicity Fibrosis Cirrhosis
CV 0 + + ++
Steatosis 0 + +++ +++
Hepatocyte 0 ++ + +
Spotty necrosis 0 ++ 0 +
Interface activity 0 0 + ++
PT 0 0 + ++
Fibrosis 0 0 ++ ++++

Central vein (CV):
0: within normal +: dilated ++: markedly dilated
Steatosis, Spotty necrosis, Interface activity:
0: no +: mild ++: moderate to marked
Hepatocytes:
0: within normal +: single cell necrosis ++: confluent or diffuse
necrosis
Portal tract (PT):
0: within normal +: expanded ++: expanded with
inflammator y infiltrate
Fibrosis:
0: no fibrosis
+: fibrosis confined to enlarged portal zones
++: fibrosis of peri -portal or portal -portal septa with intact architecture
+++: architectural distortion (septal or bridging fibrosis) without obvious cirrhosis
++++: probable or definite cirrhosis

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Figure 1: Effect of CCl 4 administration on hepatic expression of TNFSF14 protein .
A) Immunofluorescence s taining of liver sections of CC l4 treated rats showing minimal TNFSF14
expression in control group, single I.P. treated group and s ix weeks CCl 4 treated group. The
expression was increased significantly in 11 weeks group.it was noted that the expression located
mainly in the cytoplasm of cel ls located in fibrous septa (white arrow) with minimal expression in
the interior of cirrhotic nodule (blue arrows).
B) Fluorescence intensity was obtained from 5 fields of each section using ImageJ software.
Data are expressed as mean ± SEM
(a) Significan tly different from control group
(b) Significantly different from fibrosis group one -way ANOVA followed by Tukey -Kramer test for
multiple comparison test at P≤0.05

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Figure 2: Effect of CCl 4 administration on hepatic expression and localization of
TGFβRІ.
Fig.2A : Immunofluorescence staining of liver sections of CCl 4 treated rats showing minimal TGFβR1
expression in control group and also in single I.P. treated group. Six weeks CCl 4 treated group showed
maximal expression located mainly in cell membrane (yellow rectangle).Eleven weeks treatment showed
constitutive exp ression (yellow rectangle) occurred mainly at area of fibrous septa or nodule border (white
arrows) with minimal expression in cirrhotic nodule (blue arrows) .
Fig.2B : Fluorescence intensity was obtained from 5 fields of each section using ImageJ software.
Data are expressed as mean ± SEM
a) Significantly different from control group
b) Significantly different from fibrosis group one -way ANOVA followed by Tukey -Kramer test for
multiple comparison test at P≤0.05

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Figure 3: Histopathological micrograph of liver samples of CCl 4 treated groups ×235
using H and E stain. Control : liver tissue showing average PT (yellow arrows), average
central vein (red arrow), and average hepatocytes arranged in cords. Acute toxicity
model : live r tissue showing average PT (yellow arrow), spotty necrosis (black arrow),
and mild micro -vesicular steatosis. F ibrosis model : liver tissue showing expanded PT
with underlying fibrosis and fibrous septa extending from PT to PT (yellow arrows),
marked micro – and macro -vesicular steatosis. Cirrhosis model : liver tissue showing
markedly expanded PT (yellow arrows), complete nodular formation, marked micro – and
macro -vesicular steatosis.

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DISCUSSION
Administration of CCl 4 either a single I.P. dose or chronic I.P. doses for 6 or
11 weeks significantly elevated serum transaminases enzymes activities suggesting
hepatocellular damage. These results agreed with previous reports that CCl 4 significantly
increases serum transamina ses (Ahsan et al., 2009;Kalu et al., 2011 ;Dalton et al.,
2009) . This CCl 4 induced hepatic damage was reported to be due to oxidative stress
(Manibusan et al., 2007;Weber et al., 2003) . ALP activity in acute toxicity model
shows non -significant increase from control group suggesting minimal biliary injury
detected upon that model. This result opposes what was reported by Kālu’s team (Kalu et
al., 2011 ). This difference might be due difference in animal strain or route of
administration . On the other hand; ALP elevation in chronic models including fibrosis
and cirrhosis groups showed significant increase compared to control which is less than 3
times as control; a result that might suggest hepatotoxicity and mild biliary toxicity . This
matches with that previously reported by Posen and Doherty (Posen and Doherty, 1981) .
ALP activity in cirrhosis group showed significant elevation compared to fibrosis group
suggesting that chronic hepatocellular intoxication might lead to biliary i njury.
Serum albumin concentration showed only significant decrease from control
at cirrhosis group. This result agree s with previous reports that indicated the decrease in
serum albumin concentration upon decreased liver functioning tissue mass (Giannini et
al., 2005) . Meanwhile; Free radicals production and oxidative stress are main players in
liver injury especially CCl 4 induced liver injury (Manibusan et al., 2007;Weber et al.,
2003) . In our study; admin istration of CCl 4 significantly elevated tissue content of MDA
and reduced serum SOD activity. These results agreed with the previous reports that
demonstrated the great role of oxidative stress in CCl 4 induced liver injury (Kalu et al.,
2011 ;Dalton et al. , 2009;Noori et al., 2009) .
It is well known that blood parameters are greatly affected by inflammatory
conditions and liver injury. WBCs were reported to be greatly increased in inflammation
(Maury et al., 1988) . Our r esults agree with that reports . They showed significant
increase in fibrosis model However; WBCs in cirrhosis stage were lower than fibrosis
stage ; a result that may be interpreted by decreases in haemopoiesis regulatory molecules
that depends on liver synthetic function and hence show decre ase upon decline in liver
synthetic function. On the other hand RBCs, Hb and platelets showed significant decrease
in cirrhosis model; results that was due to internalisation of ferroportin molecules on cell
membranes which prevents release from iron stores (Nemeth and Ganz, 2006) in
addition to inhibitory effect of inflammatory cytokines on the release of erythropoietin
(EPO) from the kidney (Jelkmann, 1998) .
Supporting the measured biochemical data: Our findings demonstrated that
acute liver toxicit y resulted in marked spotty necrosis and confluent hepatocytes necrosis.
On the other hand prolonged administration of CCl 4 to 6 weeks produced fibrosis of peri –
portal or portal -portal septa with intact architecture while prolonged CCl 4 to 11 weeks
produce d definite cirrhosis with clear cirrhotic nodule. This is similar to what has been
reported that histopathological changes occur according to CCl 4 administration period. A
single dose of CCl 4 leads to centrizonal necrosis and steatosis (Pierce et al., 19 87),

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while continued administration leads to hepatic fibrosis, cirrhosis, and HCC (Tamayo,
1983) .
Concerning inflammatory cytokines; it was shown that TNFSF14 protein
expression showed significant upregulation in cirrhosis group only. This might suggest
that TNFSF14 was greatly involved in critical cellular processes that control cirrhosis
progression. This was quite similar to previous reports that have indicated the importance
of TNFSF14 in fibrous protein preciptation, fibroblast density and fibrosis cascades in
different tissues (Granger and Rickert, 2003;Doherty et al., 2011;Yamamoto,
2006;Herro et al., 2015a;Herro et al., 2015b) and might be an attractive marker and a
target for fibrosis therapies relevant to humans (Herro and Croft, 2015) .
The TGF -β is the principal re gulator in chronic liver injury sharing in all
stages of disease progression (Dooley and ten, 2012) . Its action begins by binding to its
receptor TGFβRI and TGFβRII (Devaux et al., 2011) . It was observed that
TGFβR1expression occurs intracellularly in the cell membrane. This agrees with
Massague and Chen reports (Massague and Chen, 2000) . It was also shown that
TGFβR1 expression was only upregulated in chronic liver toxicity; specifically phases
that showed some extent of tissue remodeling prescribe d by Devaux and his team
(Devaux et al., 2011) suggesting involvement of TGFβR1in cellular processes involved
in chronic not acute liver injury. This was similar to the previous reports in myocardial
infarction (MI) by Devaux and his team (Devaux et al., 2 011). Besides; they also showed
that the maximal expression occurs in lesion areas suggesting the direct relationship
between TGFβR1expression and lesions grade; a result that also is quite similar to
Devaux and his team reports (Devaux et al., 2011) .
CON CLUSION
In conclusion, our findings indicate, for the first time, that TNFSF14 and
TGFβRІ are upregulated in chronic not acute liver injury specifically in stages of
fibroblast activity. TNFSF14 is upregulated only in cirrhotic stages while stages before
did not. TGFβRІ is upregulated in chronic liver injury stages involving fibrosis and
cirrhosis. This may be a guide for usage of TNFSF14 and/or TGFβRІ as a candidate
marker for diagnosis and/or prognosis of chronic liver diseases and their usage as a targe t
for drug therapy in treatment of liver diseases.

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Scleroderma Pathogenesis? Arch Dermatol Res 297:333-344.

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انًهخصانعربً
دراست يقارنت بين اصاباث انكبذ انحادة وانًزينت ويذي ارتباطهى بانعايم رقى 44 ين
عىايم نخر انىرو وانًستقبم رقى ( 4 .)) نعايم اننًى انًحىل (بيتا

انسيذ جًعت انسيذ انسقا4 ،جًيم يحًذ عبذهللا 4،أحًذ يحًذ ابراهيى ينصىر 2،أحًذ ابراهيى أبىانسعىد 4،
سيذ عبذانرحيى3
1 لسُ اٌىيّياء اٌحيٛيح وٍيح اٌصيذٌح جاِعح األص٘ش-اٌما٘شج
2 لسُ األدٚيح ٚاٌسَّٛ وٍيح اٌصيذٌح جاِعح األص٘ش- اٌما٘شج
3 لسُ اٌثاثٌٛٛجٝ وٍيح اٌطة جاِعح األص٘ش- اٌما٘شج

يرٕاٚي ٘زا اٌثحث دساسح اٌفشٚق اٌىيّيائيح اٌحيٛيح تيٓ اصاتاخ اٌىثذ اٌحادج ٚاٌّضِٕح ِٓ حيث احرّاٌيح
ٚجٛد دٚس ٘اَ ٌثعط اٌّشوثاخ اٌىيّيائيح اٌحيٛيح فٝ اٌعٍّياخ اٌخٍٛيح اٌّسثثح ألِشاض اٌىثذ اٌّضِٕح. ٘زٖ
اٌّشوثاخ ٘ي اٌعاًِ سلُ (14 ) ِٓ عٛاًِ ٔخش اٌٛسَ ٚ اٌّسرمثً سلُ (1 )) ٌعاًِ إٌّٛ اٌّحٛي (تيرا.
ٌٚرحميك رٌه ذُ االسرعأح ب ( 4 ) ِجّٛعاخ ِٓ اٌجشراْ ذُ ذمسيُّٙ واالذٝ: اٌّجّٛعح اٌعاتط ح ٚ
ِجّٛعح االصاتح اٌىثذيح اٌحادج ٚ اٌّجّٛعح اٌّصاتح ترٍيف اٌىثذ ٚ اٌّجّٛعح اٌّصاتح ترشّع اٌىثذ.
ذُ ذخذيش جّيع اٌجشراْ في اٌيَٛ اٌراٌٝ الخش يَٛ في ٔٙايح ِذج اٌحمٓ عٓ غشيك االيثش ثُ ذُ فصً اٌّصً
ِٓ عيٕاخ اٌذَ ٌرحٍيً ٚظائف اٌىثذ ِثً أٔشطح أضيّاخ اٌىثذ ِثً ( ALT&AST&ALP ) ٚوزٌه ذحٍيً ٔسثح
االٌثيِٛيٓ في اٌذَ وزٌه ذُ أخز عيٕح ِٓ اٌذَ عٍٝ أثٛتح تٙا ِادج ِأعح ٌٍرجٍػ ٚرٌه ٌرحٍيً صٛسج اٌذَ اٌىاٍِح ثُ ذُ
لرً جّيع اٌجشراْ اٌّسرخذِح فٝ اٌرجشتح ٚذُ فصً األوثاد ٚغحٓ جضء ِٕٙا السرخذاِٗ فٝ ذعييٓ دالالخ صيادج حاٌح
األوسذج في ٔسيج اٌىثذ ِثً MDA ٚاٌجٍٛذاثيٓ اٌّخرضيٚايعا ٔشاغ أضيُ SOD ٚذُ حفع اٌجضء االخش ِٓ اٌىثذ
فٝ ِحٍٛي دافيذسْٛ ٚرٌه السرخذاِٙا فٝ صثغ االٔسجح تاٌٙيّاذٛوسيٍيٓ ٚااليٛسيٓ تاالظافح السرخذاِٙا فٝ ذعييٓ
ذٛاجذ تعط اٌثشٚذيٕاخ ِثً اٌعاًِ سلُ (14 ) ِٓ عٛاًِ ٔخش اٌٛسَ ٚ اٌّسرمثً سلُ (1 )) ٌعاًِ إٌّٛ اٌّحٛي (تيرا
تاسرخذاَ ذمٕيح االسرشعاع إٌّاعٝ.
ٚيّىٓ ذٍخيص ٔرائج اٌذساسح فٝ إٌماغ اٌراٌيح:
1. ِٓ اٌٛاظح ذٛاجذ اسذفاع جٛ٘شٜ فٝ أٔشطح أضيّاخ ٚظائف اٌىثذ( ALT&AST&ALP) فٝ ِشحٍرٝ
اصاتح اٌىثذ اٌّضِٕح (اٌرٍيف ٚاٌرشّع) تيّٕا االصاتح اٌحادج ذّيضخ تاسذفاع جٛ٘شٜ فٝ أٔشطح أضيّٝ
( ALT&AST) فمػ ِماسٔح تاٌّجّٛعح اٌعاتطح. تإٌسثح ٌرشويض األٌثيِٛيٓ فٝ اٌذَ فّٓ اٌٍّحٛظ اْ
ٕ٘ان أخفاض جٛ٘شٜ فٝ ِشحٍح اٌرشّع فمػ.
2. أٚظحد إٌرائج أيعا اْ ٕ٘ان اسذفاع جٛ٘شٜ فٝ ِحرٜٛ ٔسيج اٌىثذ ِٓ (MDA) ٚوزٌه أخفاض
جٛ٘شٜ فٝ ٔشاغ أضيُ ( SOD) ٚوزٌه ِحرٜٛ اٌىثذ ِٓ اٌجٍٛذاثيْٛ اٌّخرضي فٝ جّيع ِشاحً اِشاض
اٌىثذ ِماسٔح تاٌّجّٛعح اٌعاتطح.
3. وزٌه أٚظحد إٌرائج أْ أِشاض اٌىثذ اٌّضِٕح ذسثة ذٕالص جٛ٘شٜ فٝ وشاخ اٌذَ اٌحّشاء ٚاٌصفائح
اٌذِٛيح تيّٕا خاليا اٌذَ اٌثيعاء فّٓ اٌٛاظح أٔٙا اسذفعد اسذفاعا جٛ٘شيا فٝ ِشحٍح اٌرٍيف ثُ ذٕالصد فٝ
ِشحٍح اٌرشّع.
4. تإٌسثح ٌٕرائج االسرشعاع إٌّاعٝ فأٚظحد اٌذساسح اْ ٕ٘ان اسذفاع جٛ٘شٜ فٝ ذٛاجذ تشٚذيٓاٌعاًِ سلُ
(14 ) ِٓ عٛاًِ ٔخش اٌٛسَ فٝ ِشحٍح ذشّع اٌىثذ اٌزٜ اذعح أٗ يرٛاجذ اساسيا عٍٝ اٌحٛاجض اٌٍيفيح
اٌّٛجٛدج عٍي حٛاف اٌعمذج اٌشّعيح اٌّّيضج ٌٙزٖ اٌّشحٍح اٌّشظيح تيّٕا اٌّسرمثً سلُ (1 ) ٌعاًِ إٌّٛ
اٌّحٛي (تيرا) فٛجذ أٔٗ اسذفع جٛ٘شيا فٝ ِشحٍرٝ ذٍيف ٚذشّع اٌىثذ اٌزٜ ذث يٓ اْ اٌغشاء اٌخٍٜٛ ٘ٛ
اٌّىاْ األساسٝ ٌرٛاجذٖ تيّٕا ال يٛجذ اسذفاع جٛ٘شٜ فٝ ذٛاجذ ذٍه اٌثشٚذيٕاخ فٝ حاٌح االصاتح اٌحادج
ٌٍىثذ .