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I would like to thank former and current members of my lab; Jennifer, Kuljeet, Anita, Hui, Timao, Neelam, Diane Marianne, Maria and Natasha for their friendship and their help. I would like to thank my colleagues and friends for their help and support during the course of my studies; Tatjana, Andrea and Vanja. Your füendship will never be forgotten. I must also thank Heart and Stroke foundation of Canada for their support during the course of my studies. Now, last but not the least I would like to thank my wife Daliborka, my parents Dragan and Fahira, my brother Tibor, my dear grandmother Helena and Ken and Noella Broadberry for their support all these years. Thanks for not giving up on me. v11l
DEDICATION To my toughest critic, my biggest fan, my love, my best friend, my wife-Døliborku. Thank you for asking for so little and giving me so much. To my family- Broudberry's (Ken and Noella). Thank you for being my guiding light in the darkest situations. you where with me in my moments of sorrow and in my moments of joy. Thanks to you, I have never felt alone. God bless you. 1X
Page 1 and 2: il\VOLVEMENT OF RETII\OIC ACID II{
Page 3 and 4: Title: AKNOWLEDGMENTS DEDICATION LI
Page 5 and 6: IV.b.3. The uptake to peripheral ti
Page 7 and 8: II.a. Total RAR and total RXR recep
Page 9: ACKNO\ryLEDGMENTS I must say that m
Page 13 and 14: Figure: LIST OF FIGURES Page: 1. Ch
Page 15 and 16: 30. A and B The expression of anti-
Page 17 and 18: treated (ADR), trolox treated (TROL
Page 19 and 20: INTRODUCTION Adriamycin, an anthrac
Page 21 and 22: apoptosis, which will ultimately pr
Page 23 and 24: LITERATURE REVIE\il I. Adriamycin i
Page 25 and 26: Binding and alkylation of DNA Inter
Page 27 and 28: myocardial inflammation which was s
Page 29 and 30: 1990; Kusuoka et al. l99l; Olson et
Page 31 and 32: levels of antioxidant enzymes (Odom
Page 33 and 34: causing the increased leakage of el
Page 35 and 36: mechanisms which are involved in th
Page 37 and 38: to protect against adriamycin-induc
Page 39 and 40: The usage of Probucol.' Most promis
Page 41 and 42: II. Oxidative stress II.a. Introduc
Page 43 and 44: of a large array of cellular abnorm
Page 45 and 46: menstruation (Kokawa et al. 1996),
Page 47 and 48: DNA(Cohen 1997; Saikumar et al. 199
Page 49 and 50: pathogenesis of heart failure. A nu
Page 51 and 52: elonging to spontaneous hlpertensiv
Page 53 and 54: AlþTrsns Retlnolc Acld fAfRAl g€
Page 55 and 56: dehydrogenase (SDR), alcohol dehydr
Page 57 and 58: (Bavik et a|. 1991). Soon after its
Page 59 and 60: et al. 1994; Napoli 1996). The func
Page 61:
is achieved through its binding to
Page 64 and 65:
Retinoic acid signaling pathwaybegi
Page 66 and 67:
(Bavik et al. 1997). One of the mos
Page 68 and 69:
cells (Gaetano et ai. ZOot¡. The s
Page 70 and 71:
neuroblastoma, genn cell tumors and
Page 72 and 73:
presence of two distinctive pathway
Page 74 and 75:
cytochrome C release from mitochond
Page 76 and 77:
peroxidation (Sultana et a|.2004).
Page 78 and 79:
adipose tissue and to a lesser exte
Page 80 and 81:
such as; increased generation of re
Page 82 and 83:
physiological and pathological proc
Page 84 and 85:
Protective effects of PPAR y agonis
Page 86 and 87:
IIYPOTHESIS This study tests the hy
Page 88 and 89:
I.c.Collection of Tissues Hearts we
Page 90 and 91:
thoracotomy was performed and heart
Page 92 and 93:
Il.c.Western Blot Analvsis Western
Page 94 and 95:
green were counted as dead cells. T
Page 96 and 97:
RESULTS I.In Vivo Studies I.a.Gener
Page 101:
Lc. Retinoic acid receptors Three w
Page 108:
The RAR o and PPAR-õ receptors RNA
Page 113 and 114:
significantly decreased when compar
Page 116:
IL b.7. RAR alPha recePtor levels T
Page 120:
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,
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Evans,R.M. 1988. "The steroid and t
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Ghione M. Development of Adriamycin
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Herman,E., R.Young, and S.Krop . Ig
Page 165 and 166:
morphogenetic protein-2 inhibits se
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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
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Mehta,J.L., B.Hu, J.Chen, and D.Li.
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Morriss-Kay,G.M. and s.J.ward. 1999
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Notario,B., M.Zamora, O.Vinas, and
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petkovich,M., N.J.Brand, A.Krust, a
Page 181 and 182:
Ruberte,E., P.Dolle, P.Chambon, and
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Sharov,V.G., H.N.Sabbah, H.Shimoyam
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spiegelman,B.M. and J.s.Flier .1996
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Teebor,G.w., R.J.Boorstein, and J.c
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vanVeen,T.A.,H.V.vanRijen,R.F.V/ieg
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wi1liams,J.B. and J.L.Napoli. 1985.
Page 193 and 194:
peroxisome proliferator-activated r
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