Document Details
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Document Type |
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Thesis |
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Document Title |
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Effect of Histone Deacylase Inhibitor (Vorinostat) on New-Onset Diabetes Induced by Treatment with Tacrolimus تأثير مثبطات الهيستون دياسيتايلاز (فورينوستات) على مرض السكري الجديد الناتج عن العلاج بالتاكروليمس. |
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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/Aims: The immunosuppressant tacrolimus (Tacro) is one of the substantial causes of new-onset diabetes after transplantation (NODAT). The aim of this study was to evaluate whether a low dose of Vorinostat (Vorino), one of histone deacetylases inhibitors (HDAC inhibitors), is effective in improving Tacro-induced NODAT. Method: Thirty 8-week-old male Wistar rats were randomly divided into five groups, including control group, Tacro group alone (1.5 mg/kg, intraperitoneal, for 28 days), Vorino group alone (15 mg/kg, orally, for 28 days), Tacro with Vorino for 28 days and co-administration of Tacro (for 28 days) with Vorino (for 14 days). The development of diabetes was assessed by measuring serum fasting glucose, serum insulin, HOMA-IR and C-peptide level. To investigate the mechanism of Vorino, inflammatory markers (TNF-α, IL-1B),antioxidant (glutathione) and oxidant (NADPH Oxidase) markers and apoptosis marker such as caspases-3 were determined. The kidney function (creatinine and BUN) was also done. Results: The administration of Tacro for 28 days resulted in a significant increase in serum fasting glucose level and a decrease in C-peptide and insulin levels compared to the control group (p < 0.05). However, co-administration of Vorino significantly reduced hyperglycemia and increased C-peptide and insulin levels. Moreover, the combination treatment of Tacro and Vorino significantly reduced TNF-α, IL-1B, and NADPH Oxidase levels and also increased GSH level compared to Tacro-treated only group (p < 0.05). Also, Vorino improved levels of kidney parameters and histopathology. Conclusion: Vorino in low dose (15 mg/kg) induces anti-inflammatory and antioxidative effects that protect the pancreas and kidney from developing Tacro-NODAT in rats. This experimental study opens the way for further clinical trials to improve post-kidney transplantation protocol by adding Vorino to the immunosuppressive regimen. |
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Supervisor |
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Prof. Hala Abdel kawy |
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Thesis Type |
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Master Thesis |
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Publishing Year |
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1442 AH
2020 AD |
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Co-Supervisor |
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Dr. Rania Magadmi |
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Added Date |
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Sunday, March 14, 2021 |
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Researchers
| فاطمة عبدالله باخضر | Bakhdar, Fatmah Abdullah | Researcher | Master | |
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