الفهرس 
REVIEW OF LITERATUREOnly 14 pages are availabe for public view
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Abstract
The liver is the largest solid organ in our body responsible for nutrient metabolism and protein synthesis. Many liver-resident antigen-presenting cells also modulate immune regulatory function. Almost all types of liver diseases, including viral hepatitis, autoimmune hepatitis, fatty liver, alcoholic liver diseases, cirrhosis, and injury caused by drugs or toxins, were largely caused by dysregulation of immune cells in the liver.
Amphora coffaeaformis (A. coffeaeformis) contains high concentrations of numerous photosynthetic pigments, such as chlorophyll and carotenoids like -carotene and fucoxanthin, which have a range of biological activities including antimicrobial, antiobesity, anticancer, antioxidant, and other properties in many medical applications.
Biological systems have been shown to benefit from exposure to low doses of ionizing radiation. Studies done in the past suggested that exposure to low doses of ionizing radiation would trigger various mechanisms that would affect various cell types and physiological systems. Therefore, the aim of this study was to find a new therapeutic strategy to minimize hepatitis. In the current study, it was hypothesized that a combinatorial treatment may improve the outcome D-galactosamine (D-GaIN) induced hepatitis. In the current study, the effectiveness of combination between A. coffeaeformis and low dose of gamma radiation (LDR) was assessed against rat hepatitis caused by D-GalN.
To achieve this aim, in vitro study of A. coffeaeformis was carried out including; total phenolics and flavonoids as well as the free radical scavenging capacity using oxygen radical absorbance capacity (ORAC) assay. On the other hand, the in vivo study includes Sixty Four male Swiss albino rats weighing (120±20 gm) were equally divided randomly into the following 8 groups:
group I (control): rats received 1.0 ml of physiological saline solution/day by gastric gavage and were left till the end of the experiment then they were sacrificed.
group II (D-GAL group): rats were injected with D-GalN intraperitoneally in a single dose of 400 mg/kg body weight per one month.
group III (Amphora group): rats received A. Coffeaeformis (400 mg/ kg b.wt) daily extract for one month by gastric gavage.
group IV (IR): rats were exposed to single dose of gamma radiation (IR) 0.25Gy.
group V (Amphora+IR): rats were received A. caffeaeformis extract daily for one month by gastric gavage as in group III then exposed to low dose of gamma radiation as in group IV then they were sacrificed
group VI (D-GAL+Amphora): rats were injected D-GalN intraperitoneally as in group 2 then after 48 hours; rats was received A. coffeaeformis extract as in group 3.
group VII (D-GAL+IR): rats were injected D-GalN as in group 2, then after 48 hours; exposed to low dose of gamma radiation as in group 2
group VIII (D-GAL+IR+Amphora): rats were receive D-GalN as in group 2, then after 48 hours rats administrated
A. coffaeaformis extract as in group 3 and exposed to low dose of gamma radiation as in group 4.
At the end of the experiment rats were sacrificed under diethylether anesthesia, blood was collected from the heart and a part of liver tissues samples were taken and washed by saline for biochemical analysis. Other part of liver tissue were kept in and stored at 10% formalin for histopathological studies.
Chemical analyses of serum and liver tissue homogenate were statistically analyzed to evaluate the effects of
A. coffeaeformis and/or LDR through determination of liver function alanine aminotransferase, aspartate aminotransferase (ALT, AST), total protein(TP),Albumin(ALB), oxidative stress biomarkers malondialdehyde (MDA),Reduced glutathione GSH, oxidized glutathione (GSSG) and Paraoxnase-1(PON-1), inflammatory biomarkers, interleukin-6 (IL-6), tumor necrosis factor-α (TNF- α) and Intercellular adhesion molecule-1(ICAM-1), in addition to the inflammatory regulators activator of transcription 3 (STAT-3) and Nuclear Factor kabba B (NF-κB). Also, the histopathological examination was included.
The biochemical assays in D-GalN injected group revealed:
• Liver toxicity showed by a significant increase in AST and ALT activities and a significant decrease in total protein and albumin levels in the serum.
• Oxidative stress which was evidenced by a significant increase in MDA concentration in the in the liver tissue accompanied with a significant decrease in the levels of GSH and activity of PON-1accompanied by a significant increase in the level of GSSG in in the liver tissue.
• Inflammation was reported by a significant increase in the level of cytokines in the serum (IL-6 and TNF-ɑ) and adhesion molecule (ICAM-1).
• The gene expression of the inflammatory signaling molecules; NF-κB and STAT-3 should a significant upregulation in the liver tissue homogenate.
• Histological examinations revealed severe damage in liver.
Administration of A. coffeaeformis and/or exposure to LDR after the injection of D-GalN resulted in:
• Depletion of the liver enzymes (ALT and AST) level and a significant increase in total protein and albumin levels in the serum.
• Modulation of MDA level in the in the liver tissue by decreasing lipid peroxidation also, there are a significant increase in antioxidant content GSH and PON-1 associated with a significant decrease in the content of GSSG.
• Modulation of cytokines levels (TNF-ɑ and IL-6) and adhesion molecules (ICAM-1) in the serum.
• Gene expression downregulation in the inflammatory regulators NF-κB and STAT-3
Treated animals with A. coffeaeformis and/or exposure to LDR showed significant changes in tested biochemical parameter in compare to normal control group, however the improvement in the tested parmeters was greater in the combination group
(A. coffeaeformis and LDR). Concomitant with the improvement of the previous biomarkers histological finding in tissue of liver showed an ameliorative effect of A.coffeaeformis and/or exposure to LDR. According to the results obtained, it could be concluded that combination between A. coffeaeformis and LDR might a synergistic effect against D-GalN induced oxidative and inflammatory liver injury. Therefore, A.coffeaeformis and exposure to LDR have an antioxidative and anti-inflammatory potential by regulating the NF-κB/TNF-α and STAT-3/IL-6 signaling pathways.