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Rajagopalan,S., P.M.Politi, B.K.sinha, and c.E.Myers. 1988. "Adriamycin-induced free radical formation in the perfused rat heart: implications for cardiotoxicity'" Cancer Res - 48"47 66-47 69' Razeghi,P., M.E.Young, J.L.Alcorn, C.S.Moravec, o.H.Frazier, and H.Taegtmeyer' 2001. ,,Metabolic gene expression in fetal and failing human heart." Circulation' 104'2923-2931. Razeghi,P.,M.E.Young,J.Ying,C.Depre,I'P'Uray,J'Kolesar'G'L'Shipley' C. S.Moravec, P. J.D avies, o.H.Fr azier, and H. T aegtme y et. 2002. ,,Downregulation of metabolic gene expression in failing human heart before and after mechanical unloading-" Cardiology' 97:203-209 ' Regula,K.M., K.Ens, and L.A.Kirshenbaum.2003. "Mitochondria-assisted cell suicide: a license to kill." J'Mot'CeIl Cardiol' 35:559-567 ' Revis,N.W. and N.Marusic. 1978. "Glutathione peroxidase activity and selenium concentration in the hearts of doxorubicin-treated rabbits." J.Mol.CeII Cardiol' I0:945-951. Ricote,M., J.Huang, L.Fajas, A.Li, J.Welch, J.Najib, J.L.witztum, J.Auwerx,'W'Palinski, and C.K.Glass. 1998. "Expression of the peroxisome proliferator-activated receptor gamma (ppARgamma) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein." P r o c.Natl. Acad - Sci' U' 5. A. 9 5 :7 61 4-7 619' Roos,T,C., F.K.Jugert, H.F.Merk, and D.R.Bickers. 1998' "Retinoid metabolism in the skin," PharmacoL,Rev. 50:3 1 5-333' Ross,A.C., R.Zolfaghari, and J.Wei sz.20Ol. "Vitamin A: recent advances in the biotransformation, transport, and metabolism of retinoids. " Curr, Opin. Gastroenterol lT :184-192' Roucou,X., B.Antonsson, and J.c.Martinou. 2001. "Invoivement of mitochondria in apoptosis'" Cardiol' CIin' 19 :45-55' 162
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il\VOLVEMENT OF RETII\OIC ACID II{
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Title: AKNOWLEDGMENTS DEDICATION LI
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IV.b.3. The uptake to peripheral ti
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II.a. Total RAR and total RXR recep
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ACKNO\ryLEDGMENTS I must say that m
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DEDICATION To my toughest critic, m
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Figure: LIST OF FIGURES Page: 1. Ch
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30. A and B The expression of anti-
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treated (ADR), trolox treated (TROL
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INTRODUCTION Adriamycin, an anthrac
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apoptosis, which will ultimately pr
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LITERATURE REVIE\il I. Adriamycin i
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Binding and alkylation of DNA Inter
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myocardial inflammation which was s
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1990; Kusuoka et al. l99l; Olson et
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levels of antioxidant enzymes (Odom
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causing the increased leakage of el
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mechanisms which are involved in th
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to protect against adriamycin-induc
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The usage of Probucol.' Most promis
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II. Oxidative stress II.a. Introduc
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of a large array of cellular abnorm
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menstruation (Kokawa et al. 1996),
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DNA(Cohen 1997; Saikumar et al. 199
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pathogenesis of heart failure. A nu
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elonging to spontaneous hlpertensiv
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AlþTrsns Retlnolc Acld fAfRAl g€
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dehydrogenase (SDR), alcohol dehydr
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(Bavik et a|. 1991). Soon after its
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et al. 1994; Napoli 1996). The func
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is achieved through its binding to
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Retinoic acid signaling pathwaybegi
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(Bavik et al. 1997). One of the mos
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cells (Gaetano et ai. ZOot¡. The s
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neuroblastoma, genn cell tumors and
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presence of two distinctive pathway
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cytochrome C release from mitochond
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peroxidation (Sultana et a|.2004).
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adipose tissue and to a lesser exte
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such as; increased generation of re
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physiological and pathological proc
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Protective effects of PPAR y agonis
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IIYPOTHESIS This study tests the hy
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I.c.Collection of Tissues Hearts we
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thoracotomy was performed and heart
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Il.c.Western Blot Analvsis Western
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green were counted as dead cells. T
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RESULTS I.In Vivo Studies I.a.Gener
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Lc. Retinoic acid receptors Three w
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The RAR o and PPAR-õ receptors RNA
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significantly decreased when compar
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IL b.7. RAR alPha recePtor levels T
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ILb. 3. RAR sammø recEtor levels F
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ILb. 5. RXR baa recEúor levels The
Page 129: visible staining were accounted as
Page 137 and 138: DISSCUSION I. Adriamvcin CardiomvoP
Page 139 and 140: Treatment with adriamycin has been
Page 141 and 142: High RA 1 Adriamycin I oxidative st
Page 143 and 144: study as well as in others (Kumar e
Page 145 and 146: It is reported that PPAR y receptor
Page 147 and 148: expression. These effects of trolox
Page 149 and 150: REFERENCES Abdul Hamied,T.A., D.Par
Page 151 and 152: Bashor,M.M., D.O.Toft, and F.Chytll
Page 153 and 154: distribution of PPAR-alpha, -beta,
Page 155 and 156: colbert,M.C., D.G.Hall, T.R.Kimball
Page 157 and 158: Diep,Q.N., M'El Mabrouk, J.S.Cohn,
Page 159 and 160: Evans,R.M. 1988. "The steroid and t
Page 161 and 162: Ghione M. Development of Adriamycin
Page 163 and 164: Herman,E., R.Young, and S.Krop . Ig
Page 165 and 166: morphogenetic protein-2 inhibits se
Page 167 and 168: Khandoudi,N., P.Delerive, I.Berrebi
Page 169 and 170: Kusuoka,H., S.Futaki, Y.Koretsune,
Page 171 and 172: and myosin heavy chain gene express
Page 173 and 174: Mehta,J.L., B.Hu, J.Chen, and D.Li.
Page 175 and 176: Morriss-Kay,G.M. and s.J.ward. 1999
Page 177 and 178: Notario,B., M.Zamora, O.Vinas, and
Page 179: petkovich,M., N.J.Brand, A.Krust, a
Page 183 and 184: Sharov,V.G., H.N.Sabbah, H.Shimoyam
Page 185 and 186: spiegelman,B.M. and J.s.Flier .1996
Page 187 and 188: Teebor,G.w., R.J.Boorstein, and J.c
Page 189 and 190: vanVeen,T.A.,H.V.vanRijen,R.F.V/ieg
Page 191 and 192: wi1liams,J.B. and J.L.Napoli. 1985.
Page 193 and 194: peroxisome proliferator-activated r
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