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Minotti,G., P.Menna, E.Salvatorelli, G.Cairo, and L.Gianni '2004' "Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and c ardiotoxic ity." P h arm a c o I - Rev. 5 6 :1 8 5 -229' Minow,R.A. and J.A.Gottlieb. 197 5 . "Letter: Adriamycin cardiotoxicity. " Ann. Intern. Med. 82 : 85 5 -85 6. Misao,J., Y.Hayakawa, M.Ohno, S.Kato, T.Fujiwara, and H.Fujiwara. 1996' "Expression of bcl-2 protein, an inhibitor of apoptosis, and Bax, an accelerator of apoptosis, in ventricular myocytes of human hearts with myocardial infarction." Circulation. 94:1506-1512. Miyashita,T., M.Harigai, M.Hanada, andJ.C.Reed' 1994' "Identification of a p53- dependent negative response element in the bcl-2 gene." Cancer Res' 54:313I- 3 135. Miyashita,T. and J.C.Reed. 1995. "Tumor suppressor p53 is a direct transcriptional activator of the human bax gene." Cell' 80:293-299' Moasser,M.M., R.J.Motzer,K.S.Khoo, P.Lyn, B.A.Murphy, G.J.Bosl, and E'Dmitrovsky' 1995. "all-trans retinoic acid for treating germ cell tumors. ln vitro activity and results of a phase II trial." Cancer.76:680-686. Molavi,B., H.Chen, and D.Li. Preservation of LV function following ischemiareperfusion by the PPAR-gamma ligand rosiglitasone. Circulation 106(Suppl II), 168. 2005. Ref Type: Generic Moreno,P.R. and V.Fus ter. 2004. "New aspects in the pathogenesis of diabetic atherothromb o sis. " J' Am' C o I l. C ar di o l. 4 4 :229 3 -23 00' Moreno-M anzano,Y .,Y.Ishikawa, J.Lucio-C azana, and M.Kitamura. 1999 ' "Suppression of apoptosis by all-trans-retinoic acid. Dual intervention in the c-Jun n-terminal kinase-AP- 1 pathway. " J' B i ol. Ch em. 27 4:2025 | -20258' t56
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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
Page 124: 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
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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,
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Page 173: Mehta,J.L., B.Hu, J.Chen, and D.Li.
Page 177 and 178: Notario,B., M.Zamora, O.Vinas, and
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Page 191 and 192: wi1liams,J.B. and J.L.Napoli. 1985.
Page 193 and 194: peroxisome proliferator-activated r
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