Nanomedical Studies of Angiographic Contrast-Induced Renal and Vascular Injury: Clinical Implications
| Main Author: | |
|---|---|
| Language: | English |
| Published: |
Ohio University / OhioLINK
2018
|
| Subjects: | |
| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1522677857523823 |
| id |
ndltd-OhioLink-oai-etd.ohiolink.edu-ohiou1522677857523823 |
|---|---|
| record_format |
oai_dc |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Biochemistry Biomedical Research Cellular Biology Molecular Biology Pharmacology Endothelial Dysfunction Angiographic Contrast Media Nitric Oxide Peroxynitrite Oxidative and Nitroxidative Stress Renal and Vascular Injury Cardiovascular Diseases Nanosensors Pharmacological intervention |
| spellingShingle |
Biochemistry Biomedical Research Cellular Biology Molecular Biology Pharmacology Endothelial Dysfunction Angiographic Contrast Media Nitric Oxide Peroxynitrite Oxidative and Nitroxidative Stress Renal and Vascular Injury Cardiovascular Diseases Nanosensors Pharmacological intervention Dawoud, Hazem Elsaid Nanomedical Studies of Angiographic Contrast-Induced Renal and Vascular Injury: Clinical Implications |
| author |
Dawoud, Hazem Elsaid |
| author_facet |
Dawoud, Hazem Elsaid |
| author_sort |
Dawoud, Hazem Elsaid |
| title |
Nanomedical Studies of Angiographic Contrast-Induced Renal and Vascular Injury: Clinical Implications |
| title_short |
Nanomedical Studies of Angiographic Contrast-Induced Renal and Vascular Injury: Clinical Implications |
| title_full |
Nanomedical Studies of Angiographic Contrast-Induced Renal and Vascular Injury: Clinical Implications |
| title_fullStr |
Nanomedical Studies of Angiographic Contrast-Induced Renal and Vascular Injury: Clinical Implications |
| title_full_unstemmed |
Nanomedical Studies of Angiographic Contrast-Induced Renal and Vascular Injury: Clinical Implications |
| title_sort |
nanomedical studies of angiographic contrast-induced renal and vascular injury: clinical implications |
| publisher |
Ohio University / OhioLINK |
| publishDate |
2018 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1522677857523823 |
| work_keys_str_mv |
AT dawoudhazemelsaid nanomedicalstudiesofangiographiccontrastinducedrenalandvascularinjuryclinicalimplications |
| _version_ |
1719453453317570560 |
| spelling |
ndltd-OhioLink-oai-etd.ohiolink.edu-ohiou15226778575238232021-08-03T07:05:42Z Nanomedical Studies of Angiographic Contrast-Induced Renal and Vascular Injury: Clinical Implications Dawoud, Hazem Elsaid Biochemistry Biomedical Research Cellular Biology Molecular Biology Pharmacology Endothelial Dysfunction Angiographic Contrast Media Nitric Oxide Peroxynitrite Oxidative and Nitroxidative Stress Renal and Vascular Injury Cardiovascular Diseases Nanosensors Pharmacological intervention Endothelial dysfunction is a common denominator of several cardiovascular diseases (CVDs). It is fundamentally necessary to apply imaging system-angiography for diagnosis and invasive cardiology. Iodinated contrast media (CM) are widely used in angiography to visualize the cardiovascular system. Adsorption of CM molecules is necessary to attain the medical images; on the other hand, the adsorption process may contribute to toxic effects, cellular dysfunction, and serious vascular and renal injury. The incidence of CM-induced renal and vascular toxicity is about 1-2%; however, this toxic effect can increase more than 50% in patients with CVDs. The molecular mechanism of CM induced-cytotoxicity is not well understood. In this study, we hypothesized that CM induced-cytotoxicity could be due to dysfunction/uncoupling of endothelial nitric oxide synthase (eNOS) followed by a decrease of bioavailable vasodilator nitric oxide (NO) and an enhancement in the production of vasoconstrictor peroxynitrite (ONOO-). A well-established nanomedical approach, utilizing systems of nanosensors (diameter ~ 300nm) with high sensitivity, selectivity, accuracy, and a detection limit of about 1.0 nmol/L was applied to measure simultaneously CM induced NO and ONOO- concentrations in normal and dysfunctional endothelial cells. To elucidate the role of cytoprotective NO and cytotoxic nitroxidative stress induced by ONOO-, NO and ONOO- measurements were made at different concentrations of CM and at different incubation times with normal and cellular model of different diseases including diabetes, hypertension, and hypercholesterolemia. Also, animal models were used to elucidate the effect of CM on normal, diabetic and aged Wistar rats. The ratio of concentrations [NO]/[ONOO-] was used as an indicator to evaluate the level of CM induced-nitroxidative stress, coupling/uncoupling of eNOS, and function/dysfunction of endothelial cells.Exposure of endothelial cells to CM induced endothelial injury manifested by a decrease in the maximal NO concentration, an increase in ONOO- concentration and a significant reduction in [NO]/[ONOO-] ratio. This effect was more prominent in the presence of risk factors (diabetes, hypertension, and atherosclerosis) and was additive to that observed for CM alone. CM induced the upregulation of iNOS, and NADPH oxidase, in addition to eNOS uncoupling as well as enhanced the adhesion of monocytes to the surface of endothelial cells.CM negatively shift the balance between cytoprotective NO and cytotoxic ONOO- and diminish the vital function of the endothelium. The deleterious effect of CM can be mollified with pharmacological intervention. eNOS modulators (L-arginine and sepiapterin), NADPH modulators (VAS2870) as well as statins (rosuvastatin and atorvastatin) partially but significantly restored eNOS function. ONOO- concentrations were reduced while the concentrations of bioavailable NO were increased. Pre-treatment with L-arginine and rosuvastatin alone or in combination improved potentially eNOS coupling and endothelial function. The pharmacological treatment of cardiovascular system before or during angiography may be used in clinical setting to reduce the toxic effect of contrast media on the vascular and renal system. 2018-06-12 English text Ohio University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1522677857523823 http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1522677857523823 restricted--full text unavailable until 2025-06-01 This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |