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Document Type |
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Thesis |
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Document Title |
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Study of Molecular Target Mechanisms of Celecoxib Drug Induced Liver Damage and the Potential Prophylactic Impacts of Quercetin and /or Melatonin in Rats دراسة الآليات الجزيئية المستهدفة لعقار السيليكوكسيب المستحثة لتلف الكبد والآثار الوقائية المحتملة من الكرستين و/أو الميلاتونين في الجرذان |
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Subject |
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Faculty of Science |
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Document Language |
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Arabic |
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Abstract |
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The current study was designed to investigate the hepatotoxic mechanisms of celecoxib (Cele) in rats. Also, the study was extended to explore the potential ameliorative effects of melatonin (Mel) and/or quercetin (Qr) against Cele hepatotoxicity. Cele (50mg/kg/day) was administered orally to rats for 30 successive days. Mel (12mg/Kg/day) and Qr (10mg/kg/day) were administered orally to rats concurrently with Cele administration daily for 30 days. Rats were divided into five groups, GI, served as normal group; GII, Cele treated group; GIII, Cele treated group concurrently with Mel; GIV, Cele treated group concurrently with Qr; GV, Cele treated group concurrently with the combination of the two agents. The prophylactic efficiency of Mel and/or Qr on hepatic histomorphological damage in rats was also investigated. The results showed that administration of Cele significantly induced hepatic mitochondrial damage as manifested by depletion in hepatic succinate dehydrogenase (SDH) activity and adenosine triphosphate (ATP) with a concomitant increase in adenosine diphosphate (ADP) in Cele administered group in comparison to normal group. Cele also induced hepatic oxidative stress as observed by increases in hepatic malondialdehyde (MDA), nitric oxide (NO) and oxidative deoxyribonucleic acid (DNA) damage along with depletion in antioxidant enzymes, catalase (CAT) and glutathione reductase (GR). In addition, the results demonstrated that Cele caused increases in the hepatic inflammatory and fibrogenetic cytokines, namely tumor necrosis factor-α (TNF-α) and transformation growth factor-β (TGF-β) as well as in, hepatic caspase-3 (apoptosis enzyme) and hydroxyproline (index of hepatic fibrogenesis) levels. The hepatotoxic effects of Cele were documented by alteration in serum liver function markers (ALT and AST, albumin) as well as in liver histologic architecture in Cele treated group compared with normal one. Co-administration of Cele intoxicated rats with Mel and/or Qr, effectively ameliorated the deterioration in the studied parameters compared with Cele intoxicated rats. The combination of the two agents was the most effective one in ameliorating these parameters as well as the histomorphologic liver architecture. In conclusion: The data showed that Cele could induce liver damage through several mechanisms. Co-intake of Mel and/or Qr could protect the liver tissues from the damaging impact of Cele which was more pronounced in rats treated with the combination of the two agents. |
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Supervisor |
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Prof. Dr. Jehad Mustafa Yousef |
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Thesis Type |
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Master Thesis |
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Publishing Year |
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1441 AH
2020 AD |
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Co-Supervisor |
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Prof. Dr. Azza Mostafa Mohamed |
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Added Date |
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Monday, June 15, 2020 |
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Researchers
| امتنان سامي سليماني | Sulimani, Emtenan Sami | Researcher | Master | |
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