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Document Type |
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Thesis |
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Document Title |
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CHEMOSENSITIZING AND CARDIOPROTECTIVE EFFECTS OF MARINE ASTAXANTHIN IN DOXORUBICIN TREATED ANIMALS تحفیز فعالیة عقار الدكسوروبیسین والوقاية من تأثیراته السمیة على القلب بواسطة مادة الأستازانثین البحري في حیوانات التجارب |
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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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Doxorubicin (DOX) is an anthracycline used as a chemotherapeutic drug to treat many types of cancers. Unfortunately, DOX clinical usefulness is limited by its serious cardiotoxicity which may lead to congestive heart failure. Many strategies have been evaluated to increase the DOX efficacy and reduce its cardiotoxicity. The aim of this work was directed to investigate whether marine astaxanthin (ATX), a xanthophyll carotenoid with a potent antioxidant effects, can sensitize Ehrlich ascites carcinoma (EAC) cells to the action of DOX and provide cardioprotective effects against DOX-induced cardiotoxicity.
To evaluate these effects the antitumor activities of DOX in presence and absence of ATX have been studied through evaluation of mean survival time (MST) and long term survivor (LTS %) of tumor-bearing mice. In addition, the molecular effects by which ATX may induce this chemosensitization have been examined through evaluation of DOX uptake into the tumor cells, apoptosis measurement, analysis of cell cycle and the measurement of p53 gene expression in EAC cells after DOX treatment in presence and absence of marine ATX.
The results showed that the treatment with ATX before DOX administration significantly increased the MST of tumor bearing mice to 41.1 days with 80% LTS compared with DOX treated mice which have MST of 32.5 days with 30 % LTS. Although the MST of ATX treated mice showed a significant increase in MST to 20 days, there was no significant difference in LTS between control and ATX treated groups has been observed.
Moreover, the present study showed a significant increase in DOX uptake into ATX treated EAC cells compared to EAC cells withdrawn from mice treated with DOX alone.
In addition, there was a significant increase in the accumulation of EAC cells in G2/M phase and in the percentage of early apoptotic EAC cells withdrawn from ATX + DOX treated mice in comparison with EAC cells treated with DOX alone. Also, addition of ATX to DOX in the treatment regimen showed a significant increase in the expression of p53 gene by almost 2 folds compared with cells treated with DOX alone. On the other hand, addition of ATX to DOX treatment showed a cardioprotective effect against DOX-induced cardiotoxicity manifested by a significant decrease in the serum level of cardiac enzymes, CPK and CK-MB, and heart tissues malondialdehyde (MDA) levels compared to those in DOX treated rats. Also, this addition significantly increase the level of serum total antioxidant capacity (TAC) and heart tissue levels of reduced glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) compared to the corresponding levels in rats treated with DOX only. Histopathological investigations of the cardiac tissues have confirmed the biochemical studies, where addition of ATX to DOX showed that the fragmentation of the muscle fiber revealed normal with central vesicular nuclei and prevented a marked disruption of normal cardiac architecture that resulted from DOX treatment. In conclusion, ATX has increased the cytotoxic activity of DOX against the growth of EAC cells and provided excellent cardioprotective effect against its cardiotoxicity in normal rats. |
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Supervisor |
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Prof. Zoheir A. Damanhouri |
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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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Co-Supervisor |
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Dr. Huda M. Alkreathy |
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Added Date |
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Friday, June 26, 2020 |
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Researchers
| علي عوض القحطاني | AlQahtani, Ali Awadh | Researcher | Master | |
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