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Document Type |
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Thesis |
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Document Title |
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Hepatoprotective Effects of Vorinostat (Suberoylanilide Hydroxamic Acid: A Histone Deacetylase Inhibitor) in Immunological Liver Injury in Rats Model التأثير الإيجابي لحماية الكبد لحمض الهيدروكسيمك سبيريونيل أنالايد (فورينوستات)، المانع للإنزيم المسؤول عن إزالة الأسيتيل من الهستون بـإستخدام نموذج تليف كبد مناعي في الجرذان |
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Subject |
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Faculty of medicine |
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Document Language |
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Arabic |
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Abstract |
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Background: One of the main causes for the development of chronic liver disease is autoimmune hepatitis (AIH). There is no clear etiological factor for AIH occurrence and no drug has been approved for its treatment. Vorinostat, a Histone deacetylase inhibitor (HDACi) has been shown to reduce inflammation.
Purpose: Our aim was to explore the protective potential of vorinostat in a rat model of AIH induced by concanavalin A (Con A).
Methods: The rats were randomly divided into 4 groups; control group, con A (20mg/kg/iv/wk) group, vorinostat (15 mg/kg/day p.o) group and Con A with vorinostat group. Blood and liver samples were collected at the end of the fourth and eighth weeks for biochemical and histopathological examinations. Laboratory experiments included: colorimetric assay of liver enzymes, assessment of hydroxyl-proline level, measurement of level of tumor necrosis factor, gene expression of Interleukin 1 and tumor growth factor 1 , histopathological analysis of Hematoxylin and Eosin (H and E) and Masson trichromes, and immunohistochemistry of alpha smooth muscle actin.
Results: Results revealed that administration of Con A elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) liver enzymes, which were reduced to 52.8% and to 61.8% respectively on simultaneous administration of Vorinostat drug in combination therapy as compare to Con A group. Furthermore, Vorinostat in the combination group reduced fibrosis and diminished apoptosis as deduced by the decrease in the hepatic hydroxyproline content of the liver and tumor necrosis factor-alpha levels.
Relative gene expression analysis of interleukin 1 and transforming growth factor beta were significantly decreased in combination group treated with vorinostat. Histopathological analysis and immunohistochemistry results showed that administration of vorinostat in combination group significantly restored the well organized structure of the liver, decreased initial inflammation produced by Con A, reduced liver fibrosis and mitigated hepatic stellate cell’s activities. Administration of vorinostat alone has no significant effects on the structural integrity of liver.
Conclusion: In conclusion, administration of vorinostat in Con A model of autoimmune hepatitis, significantly decreased liver inflammation and fibrosis. So vorinostat might show a new protective approach for management of autoimmune hepatitis and its complications.
Keywords:
Vorinostat, Concanvalin A, hepatitis, Autoimmune hepatitis, Hydroxyproline. |
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Supervisor |
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Dr. Hala Owais |
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Thesis Type |
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Doctorate Thesis |
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Publishing Year |
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1441 AH
2020 AD |
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Added Date |
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Saturday, May 30, 2020 |
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Researchers
| عائشة الحداد | Alhaddad, Aisha | Researcher | Doctorate | |
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