The effects of radioprotectant amifostine on irradiated rat brain and liver tissues

Download
index.pdf
2010
Çakmak, Gülgün
Show full item record
155
views
71
downloads
Amifostine is the only approved radioprotective agent by the Food and Drug Administration for reducing the damaging effects of radiation on healthy tissues. In this study, the effects of ionizing radiation on rat liver microsomal membrane and brain tissue and the protecting effects of amifostine on these systems were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated and liver microsomal membranes and different regions of the brain of these rats were analyzed using FTIR spectroscopy, FTIR microspectroscopy and synchrotron FTIR microspectroscopy. The first part of this study revealed that ionizing radiation caused a decrease in the total lipid content and CH2 groups of lipids, an increase in the carbonyl esters, olefinic=CH and CH3 groups of lipids in the white matter and grey matter regions of the brain, which could be interpreted as a result of lipid peroxidation. In addition, radiation altered the protein structure of the brain. Amifostine caused significant protective effect against all the radiation induced damages in the brain. In the second part of the study, FTIR results showed that radiation induced a decrease in the lipid/protein ratio and a degradation of lipids into smaller fragments that contain less CH2 and more carbonyl esters, olefinic=CH and CH3 groups in microsomal membranes. In addition, radiation caused an alteration in the secondary structure of proteins, an increase in lipid order and a decrease in the membrane dynamics. Amifostine prevented all the radiation induced compositional, structural and functional damages in the liver microsomal membranes.
Drug resistance in microorganisms., Multidrug resistance.
http://etd.lib.metu.edu.tr/upload/12612591/index.pdf
https://hdl.handle.net/11511/20048
Graduate School of Natural and Applied Sciences, Thesis

Suggestions

Reversal of multidrug resistance in mcf-7 breast adenocarcinoma cell line by silencing interleukin 6 with RNA interference
Çakmak, Neşe; Gündüz, Ufuk; Department of Biology (2013)
Multidrug resistance (MDR) in cancer is characterized by development of resistance to several unrelated drugs upon long time administration of a certain type of chemotherapeutic agent. In doxorubicin resistant MCF-7 cell line, resistance is developed mainly by upregulation of MDR1 gene which encodes an ABC transporter protein known as P-glycoprotein. Interleukin 6 (IL-6) is a cytokine which acts as a growth factor for certain cell types including some cancer cells. IL-6 is found at high levels in cancer pat...
Investigation of the role of programmed cell death 10 (PDCD10) protein in multidrug resistance
Urfalı Mamatoğlu, Çağrı; Gündüz, Ufuk; Department of Biology (2018)
Drug resistance, a major obstacle in chemotherapy, is the sum of several cellular alterations including resistance to induction of apoptosis. Apoptosis is a well-regulated cell death mechanism which is controlled by several signaling pathways and a vast number of proteins. Alterations in the proteins involved in the apoptotic regulation have been associated with drug resistance in cancer. Programmed Cell Death 10 (PDCD10) protein is a novel apoptotic regulator that is recently linked to the modulation of ce...
Effect of cobalt-60 (gamma radiation) on multidrug-resistant multiple myeloma cell lines
Mutlu, Pelin; Ural, A. Ugur; Avcu, Ferit; Dirican, Bahar; Beyzadeoglu, Murat; Gündüz, Ufuk (2011-07-01)
Emergence of resistance to chemotherapy and radiotherapy is a major obstacle for the successful treatment of MM (multiple myeloma). Prednisone, vincristine and melphalan are commonly used chemotherapeutic agents for the treatment of MM. In the current study, we examined the presence of possible cross-resistance between these drugs and gamma (gamma) radiation. Prednisone, vincristine and melphalan resistant RPMI-8226 and U-266 MM cells were generated by stepwise increasing concentrations of the drugs. The se...
Amifostine, a radioprotectant agent, protects rat brain tissue lipids against ionizing radiation induced damage: An FTIR microspectroscopic imaging study
Cakmak, Gulgun; Miller, Lisa M.; Zorlu, Faruk; Severcan, Feride (Elsevier BV, 2012-04-15)
Amifostine is the only approved radioprotective agent by FDA for reducing the damaging effects of radiation on healthy tissues. In this study, the protective effect of amifostine against the damaging effects of ionizing radiation on the white matter (WM) and grey matter (GM) regions of the rat brain were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated at a single dose of 800 cGy, decapitated after 24 h and the brain tissues of these...
Reversal of breast cancer resistance protein mediated multidrug resistance in MCF7 breast adenocarcinoma cell line
Urfalı, Çağrı; Gündüz, Ufuk; Department of Biology (2011)
Resistance to various chemotherapeutic agents is a major problem in success of cancer chemotherapy. One of the primary reasons of development of multidrug resistance (MDR) is the overexpression of ATP binding cassette (ABC) transporter proteins. Breast cancer resistance protein (BCRP) belongs to ABC transporter family and encoded by ABCG2 gene. BCRP is mainly expressed in MDR1 (P-glycoprotein) lacking breast cancer cells. Overexpression of BCRP leads to efflux of chemotherapeutic agents at higher rates, the...
Citation Formats
G. Çakmak, “The effects of radioprotectant amifostine on irradiated rat brain and liver tissues,” Ph.D. - Doctoral Program, Middle East Technical University, 2010.
METU IIS - Integrated Information Service open@metu.edu.tr