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العنوان
Evaluation of a novel 5-aminolevulinic acid derivative and its efficacy in destruction of tumors by photodynamic therapy /
المؤلف
Mohamed, Manar Refaat Abd El-Khalek.
هيئة الاعداد
باحث / منار رفعت عبدالخالق محمد
مشرف / محمد عبد الحافظ الفار
مشرف / سمير بهجت عبدالرازق بندق
مناقش / فاتن زهران محمد
مناقش / السعيد الشربيني السعيد
الموضوع
photodynamic therapy. free radicals. antioxidants.
تاريخ النشر
2010.
عدد الصفحات
148 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
Chemistry (miscellaneous)
تاريخ الإجازة
1/1/2010
مكان الإجازة
جامعة المنصورة - كلية العلوم - قسم الكيمياء
الفهرس
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Abstract

The present study was carried out to synthesized a novel 5-aminolevulinic acid ester derivative from reacting ALA with β-citronellol and tested its potential for treatment of tumors by photodynamic therapy in comparison to the widely used agents, ALA and Me-ALA . The most important results of the present study are summarized and discussed as following: 1. Flow cytometry studies revealed G0/G1 cell cycle arrest during the PDT-mediated response. cells following 3 h incubation with 5- ALA and β-citronellol-ALA ester and ex-vivo irradiation exhibited a diminished G0/G1 phase and a highly significant increase in apoptotic cells (sub-G1) in comparing to the control. 2. The smallest ascetics tumor volume was observed in the case of treatment with ALA-β-citronellol ester derivative. The novel ester derivative was a significantly better agent than either ALA or Me-ALA at preventing or inhibiting growth of tumors due to a rather effective PpIX production. 3. Oxidative stress, MDA was significantly increased in EAC treated with various chemicals compared to the control and this give an indication for EAC treatment, while NO was significantly decreased when compared to the control which lead to increase in PDT effect. 4. Antioxidant enzyme (SOD) was significantly increased in EAC treated with various chemicals compared to the control, this changes in SOD activity show that photodynamic action generates oxidative stress in the treated cells. 5. PDT of solid tumors show that ALA HCl formulation showed only partial response post PDT treatment, and had not developed complete destruction or disappearance in tumors in any case. This indicating a partial response to PDT using parent compound ALA HCl, our -Citronellol-ALA ester derivative showed a complete destruction of tumors within 2-3 weeks post treatment. The tumors never regrow or return again. This indicating a complete response to PDT using our novel ALA-β-Citronellol ester derivative. In conclusion the ALA-β-Citronellol ester derivative is a novel and highly effective agent for PDT of tumors. Ex vivo studies show that it is highly effective at inducing apoptosis in EAC cells following irradiation of cells previously incubated with the relevant agents. It is substantially better than either ALA.HCl or ALA methyl ester at inhibiting growth of tumors involving EAC cells following inoculation of healthy animals with cell solutions that had been extracted from animals impregnated with EAC cells and incubated with the appropriate agents prior to irradiation with light. It is also substantially better and superior to ALA.HCl for destruction of large tumors following topical application to the skin covering solid tumors followed by irradiation with light. It is a very promising safe agent -as prepared from natural materials for practical PDT. The photos showed impressive complete response in mice treated with our novel ALA-β-Citronellol ester derivative.