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العنوان
Impact of Propolis Loaded Nanoparticles on Toll Like Receptors 4 in Experimental Model of Breast Cancer /
المؤلف
Alshutfa, Shadi Mohammed Abdullah.
هيئة الاعداد
باحث / شادى محمد عبد الله الشطفة
مشرف / ماجدة عبد الغنى مجاهد
مشرف / سارة عبد الصبور شاكر
مناقش / وفاء محمود السيد
مناقش / طارق مصطفى محمد
الموضوع
Biochemistry Chemistry.
تاريخ النشر
2022.
عدد الصفحات
108 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
Biochemistry
تاريخ الإجازة
2/10/2022
مكان الإجازة
جامعة الاسكندريه - معهد البحوث الطبية - Biochemistry
الفهرس
Only 14 pages are availabe for public view

from 108

from 108

Abstract

tumor in women is breast cancer, and its incidence has been rising every year. In addition, breast cancer is developing at younger ages. Currently available anti-cancer therapies, such as chemotherapy, radiation therapy, and surgery, are somewhat effective, but their side effects outweigh their benefits. A combination of antioxidants may be a powerful adjuvant, preventive treatment for cancer because, according to numerous studies, they reduce the damage caused by free radicals. The negative effects of chemotherapy and radiotherapy on healthy cells are many, and cancer cells are frequently drug-resistant. High levels of reactive oxygen species (ROS) can cause oxidative stress, which eventually triggers a variety of chronic diseases like atherosclerosis, cancer, diabetes, and other degenerative diseases in humans. This stress affects cell structures such as lipids and membranes, proteins, and nucleic acids. propolis (honey bee glue) has been used as a popular folk medicine for its antibacterial, anti-inflammatory, antioxidative, immunostimulatory and carcinostatic properties. Nanoparticles are frequently employed in business and the healthcare sector for a variety of purposes, including antimicrobials. They are employed as drug carriers in medicine to more effectively deliver drugs to the target region by encapsulating a variety of therapeutic components, including drug molecules, proteins, and peptides. The aim of this study was to examine the effect of Egyptian Propolis loaded nanoparticle on expression of TLR-4, High-mobility group box-1 protein (HMGB1), mir223, NF-kB, and MMP-9, in breast cancer induced by implementation in mice.
The study was conducted on 60 healthy Balb/c female mice 10-12 weeks old with an average weight of 20-25 g that was divided into 2 groups: group 1 (Normal group): Ten normal mice served as the control group and received normal saline. group 2 (induced - breast cancer group): Mammary tumors was induced in 50 mice by Ehrlich ascites carcinoma (EAC) cells that was implanted subcutaneously in the mammary fat pad of mice by inoculation of 0.2 mL of 2×105 tumor cells in physiological solution until the tumor reached a considerable size. That was divided into five subgroups: group 2a (untreated group): Ten untreated tumor bearing mice were only receive normal saline. group 2b (5-florouracil treated group): Ten tumor bearing mice were treated with 5-florouracil at a dose of 20 mg /kg ip for 9 days. group 2c (propolis treated group): Ten tumor bearing mice were treated with propolis at dose of 4 mg/kg orally for 9 days. group 2d (propolis loaded nanoparticles treated group): Ten tumor bearing mice were treated with propolis loaded nanoparticles at a dose of 4 mg /kg orally for 9 days. group 2e (propolis loaded nanoparticles and 5-florouracil treated group): Ten tumor bearing mice were treated with propolis loaded nanoparticles at a dose of 4 mg /kg and with5-florouracil at a dose of 20 mg /kg.
By the end of the specified treatment period, animals were lightly anesthetized and blood was collected via cardiac puncture and centrifuged (800 rpm, 4°C, 20 min) to separate the serum. A part of breast tissue showing tumor was fixed in 10% formalin for histopathological analysis using hematoxylin-eosin stain and the remaining part of tumors were processed for molecular (TLR-4, HMGB1, mir223, NF-kB, and MMP-9) expressions and biochemical analysis (AST, ALT, Urea, Creatinine, MDA, TAC, GSH, GR, SOD and Catalase). All samples were stored at -80°C. Animals’ bodies were frozen until incineration.
Summary and Conclusions
80
5-FU, PEE, ProEE-NLC and combined treated experimental mice models injected with EAC showed a significant reduction in (the tumor volume, MDA, urea creatinine, ALT and AST activities and MMP9, VEGF TLR4, HMGB1, NF-kB expressions) also re-elevation in (the activities of TAC and GSH, GR, SOD, Catalase enzymes, and p53, miRNA 223 expressions) as compared to mice in the untreated EAC group cells and treated with. Among the five treated groups, the best antitumor effect showed in ProEE-NLC treated mice.
from this study we concluded that:
 ProEE-NLC has powerful therapeutic effects in the reduction tumor volume in EAC mice model.
 The ProEE-NLC targets multiple pathways that play vital roles in the inhibition of EAC including impaired oxidative stress (decline of serum and tissue MDA), regain antioxidant balance (elevation TAC, GSH, GR, SOD and Catalase) of and down regulation of MMP9, VEGF TLR4, HMGB1, NF-kB expressions and upregulation p53 and miRNA 223 expressions.
 All of these effects together with the safety and no adverse effects of ProEE-NLC make it a promising therapeutic agent against EAC.
 Further investigation is required to elucidate the particular component of ProEE, NLC and ProEE-NLC that is responsible for the anti-EAC effect documented with the treatment.