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العنوان
The Possible Toxic Effect of Gold Nanoparticles on Cardiac Muscle of Rats: Cardioprotective Role of Aspirin /
المؤلف
Ghareeb, Asmaa Ahmed Mohamed.
هيئة الاعداد
باحث / أسماء احمد محمد غريب
مشرف / سوزان محمد عبدالتواب
مشرف / وفاء محمود السيد عبدالرحيم
مشرف / ثناء ابراهيم احمد شلبى
مشرف / بثينة فؤاد محمود
الموضوع
Biochemistry. Chemistry.
تاريخ النشر
2018.
عدد الصفحات
130 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
Biochemistry
تاريخ الإجازة
24/12/2018
مكان الإجازة
جامعة الاسكندريه - معهد البحوث الطبية - الكيمياء الحيوية
الفهرس
Only 14 pages are availabe for public view

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Abstract

Recent years have seen a great deal of interest in the use of nanotechnology in various fields and most importantly the medical one. There is an explosion in the number of studies showing the variety of medical applications of nanotechnology. Nanoparticles have become widely utilized because of their unique properties and diverse applications Toxicity of nanoparticles is a critical factor when evaluating their biomedical potential.They are highly reactive and may enter cells that they would otherwise have no access to.This is due to their small size and high surface area. Furthermore, the underlying interactions of nanoparticles with biological systems is a key feature for understanding their biological impact, which could perhaps be exploited to mitigate unwanted toxic effects.Among the various nanoparticles, gold nanoparticles have attracted enormous scientific and technological interest due to their ease of synthesis, chemical stability, and unique properties. Gold nanoparticles can be synthesized into a variety of shapes and sizes.They have become ideal candidates as imaging contrast agents, therapeutic agents, and drug delivery vehicles. Nonetheless, a better fundamental understanding of gold nanoparticles behavior in biological systems needs to be addressed.The cytotoxicity mediated by gold nanoparticles and their effect on various organs are of great concern. Oxidative stress has been highly proposed as an elicited mechanism for gold nanoparticles mediated cytotoxicity by overproduction of free radicals and activating pathways of oxidative stress.Cardiovascular diseases are the leading cause of mortality worldwide. Studies have shown that any acute or chronic cardiac stress conditions, resulting in a relative deficit in the myocardial antioxidant reserve and excess in free radicals production are associated with an increase in myocardial oxidative stress that plays a significant role in various heart diseases.Brain natriuretic peptide (BNP) has emerged as the most useful biomarker for cardiac diseases. Its major advantage over the other natriuretic peptides is the fact that it is produced predominantly in the ventricles and could be used to follow dynamic alterations in myocardial performance. Another important cardiac marker is creatine kinase isoenzyme (CK-MB). The primary source of CK-MB is the myocardium and the appearance of elevated CK-MB level is highly specific and sensitive for myocardial injury. Aspirin has been reported to provide effective beneficial protection against many cardiovascular pathological conditions. It has been highly proposed as a potent antioxidant, which could markedly reduce the vascular production of free radicals.The present study was devoted to investigate the possible toxic effect of gold nanoparticles on cardiac muscle of rats and to assess the possible cardioprotective role of aspirin.Gold nanoparticles were synthesized with diameter nearly 20nm. Morphology and size of gold nanoparticles were determined by transmission electron microscopy, zeta potential and particle size analysis which, revealed the presence of completely spherical gold nanoparticles with smooth surfaces. The absorption spectra of gold nanoparticles were also Summary and Conclusion 84 determined by UV-visible spectrophotometer. Data showed that the plasmon absorption of gold nanoparticles was clearly visible and their maximum absorption peaks were at 530nm.The present study was carried out on 60 male albino rats of body weight ranging from 165 to 180g. Rats were randomly divided into 3 groups (20 rats each); group I: rats were injected intraperitoneally with saline (control group), group II: rats were injected intraperitoneally with a suspension of gold nanoparticles of about 20nm with a dose of 400μg/kg body weight for 14 days and group III: rats were intraperitoneally injected with a suspension of gold nanoparticles of about 20nm with a dose of 400μg/kg body weight in combination with an oral dose of aspirin (5mg/kg body weight) for 14 days. At the end of the study, blood samples and heart tissue samples in the different studied groups were collected for the intended biochemical and histopathological investigations.The current study showed that, the level of malondialdehyde (MDA), nitric oxide end products (NOx), advanced oxidation protein products (AOPPs) and 8-hydroxydeoxyguanisine (8-OHdG) were significantly higher in gold nanoparticles injected group as compared to controls. While, the total antioxidant capacity measured as ferric reducing antioxidant power (FRAP) was significantly lower in gold nanoparticles injected group compared to controls. The effect of gold nanoparticles on cardiac hypertrophy was also studied. The relative heart weight to total body weight and BNP were significantly elevated in gold nanoparticles injected group compared to control group revealing the possible cardiac hypertrophic role of gold nanoparticles.Gold nanoparticles markedly altered the lipid profile of rats. The level of triglycerides,cholesterol, low density lipoproteins (LDL) were significantly higher in gold nanoparticles injected group compared to controls. Where, the level of high density lipoproteins (HDL)<was significantly lower compared to the same group.In addition, the activity of aspartate aminotransferase (AST), alanine aminotransferase(ALT) and CK-MB were significantly higher in gold nanoparticles injected group compared to control group. Further, correlation studies indeed showed a direct correlation between the level of BNP and the level of: MDA, NOx, 8-OHdG and relative heart weight to total body weight in gold nanoparticles injected group. All these findings favor the possible cytotoxic effects of gold nanoparticles through oxidant generation in tissues and DNA, depleting total antioxidant capacity and inducing cardiac hypertrophy.Surprisingly, gold nanoparticles injection accompanied by aspirin supplementation caused marked reduction in relative heart weight to total body weight, liver function enzymes (ALT and AST), MDA, NOx, AOPPs, 8-OHdG, CK-MB and BNP and improvement of lipid profile, with concomitant increase in FRAP compared to the group that was only injected with gold nanoparticles. Those results may suggest the possible antioxidant, antihypertrophic and cardioprotective properties of aspirin.Histopathological examination of heart tissues in control group and gold nanoparticles injected groups was carried out in order to assess the histological changes that resulted from intraperitoneal injection of 20nm gold nanoparticles with and without aspirin supplementation. Heart tissue sections in gold nanoparticles injected group revealed various degree of cardiac tissue injury and degeneration. While, those changes were less prominent in gold nanoparticle injected group and supplemented with aspirin.Summary an