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sani,B.p. and D.L.Hill.lgl4."Retinoic acid: abinding protein in chick embryo metatarsalskin.''Biochem,Biophys.Res.Commun.6|:7276-1282. Sano,K., T.Takayama, K.Murakami, I.saiki, and M.Makuuchi' 2003' "Overexpression of retinoic acid receptor aþha in hepatocellular carcinoma'" Clin'Cancer Res' 9:3679-3683. Santostasi,G., R.K.Kutty, and G.Krishna. 1991. "Increased toxicity of anthracycline antibiotics induced by calcium entry blockers in cultured cardiomyocytes'" Toxicol.Appl. Pharmacol. 1 08: 1 40- 149' Sarter,B. 2002. "Coenz¡rme Q10 and cardiovascular disease: a review'" J. C ar di ov as c.Nur s. | 6 :9 -20' Sawyer,D.B., D.A.Siwik, L.xiao, D.R.Pimentel, K.Singh, and w.s.colucci' 2002' "Role of oxidative stress in myocardial hypertrophy and failure." J'Mol'cell cardiol' 34:379-388. Schuchter,L.M., M.L.Hensley, N.J.Meropol, and E.P.Winer. 2002. "2002 update of recommendations for the use of chemotherapy and radiotherapy protectants: clinical practice guidelines of the American Society of Clinical Oncology'" J. Clin. Onco l. 20 :289 5 -2903' Scott,W.J., Jr., R.IValter, G.Tzimas, J.o.sass, H.Nau, and M.D'collins. 1994' ,,Endogenous status of retinoids and their cytosolic binding proteins in iimb buds of chick vs mouse embryos'" Dev'Biol' 165:397 -409 ' Sendo,F., H.Tsuchida, Y.Takeda, S.Gon, H.Takei, T.Kato, o.Hachiya, and H'watanabe' 1996. "Regulation of neutrophil apoptosis--its biological significance in infl ammation and the immune response. " Hum. C ell. 9 :21 5 -222. Shamberger,R. J., T.L.Andreone, and C'E.Willis. lg7 4' " Antioxidants and cancer' fV' Initiating activity of malonaldehyde as a carcino gen'" J'Natl'cancer Inst' 53:1'771-1773. 164
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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
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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 and 180: petkovich,M., N.J.Brand, A.Krust, a
Page 181: Ruberte,E., P.Dolle, P.Chambon, and
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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