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Protective effects of PPAR y agonists against ischemia-reperfusion damage to heart are attributed to a number of factors such as inhibition of fUN-kinase, attenuation of INOS, inhibition of NF-kB and decrease in TNF-c¿ and TGF-B signaling (I\4olavi et al. 2005; Shiomi et al. 2002;'Wayman et al. 2002). The usage of PPAR y agonists in clinical setting is currently limited due to the reports of the development of peripheral edema and increased occurrence of congestive heart failure in some patients (Krentz et al. 2000; Wooltron E 2002). Another setback for the usage of PPAR y agonists therapy in patients is the fact that of PPAR y receptors are still not definitely identified in heart tissue which questions their direct effects on heart tissue and implies the existence of an indirect protective mechanisms Q.{ikolaidis and Levine 2004). The usage of PPAR a agonists was also shown to cause the protection against heart failure. It is suggested that the usage of PPAR cr agonists in heart failure may reactivate the metabolism of free fatty acids by heart muscle thus preventing the detrimental effects of glucose utilization. The usage of PPAR a agonist was shown to be beneficial against the myocardial remodeling process induced by pressure-overload phenomenon (Ogata et aL.2002). The same study has shown that treatment with PPAR a agonist-fenofibrate was able to prevent the increase in the expression of prepro-ET-i and collagen type I and type II mRNA induced by the pressure overload (Ogata et al.2002) . This coincided with a decrease in interstitial and peri-vascular cardiac fibrosis (Ogata et al. 2002). The usage of fenofibrate was also shown to have a benef,rcial effects of inflammation and collage deposition in hearts of ANG Il-infused rats (Diep et al.2002a). The study using a cre-loxP-mediated cardiomyocyte-restricted deletion of PPAR p/ô in 66
mice has reported that the lack of PPAR B/õ will result in the disruption of fatty acid oxidase metabolism and myocardial lipid accumulation and will lead to the development of congestive heart failure (Cheng et al. 2004). In this literature several gaps in our knowledge on the role of oxidative stress and apoptosis in the pathogenesis of adriamycin-induced heart failure have been identified. We have focused this study on the role of retinoic acid, oxidative stress and apoptosis as mentioned in introduction section. 67
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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
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 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
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DISSCUSION I. Adriamvcin CardiomvoP
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Treatment with adriamycin has been
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High RA 1 Adriamycin I oxidative st
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study as well as in others (Kumar e
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It is reported that PPAR y receptor
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expression. These effects of trolox
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REFERENCES Abdul Hamied,T.A., D.Par
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Bashor,M.M., D.O.Toft, and F.Chytll
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distribution of PPAR-alpha, -beta,
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colbert,M.C., D.G.Hall, T.R.Kimball
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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
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Herman,E., R.Young, and S.Krop . Ig
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morphogenetic protein-2 inhibits se
Page 167 and 168:
Khandoudi,N., P.Delerive, I.Berrebi
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Kusuoka,H., S.Futaki, Y.Koretsune,
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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 and 182:
Ruberte,E., P.Dolle, P.Chambon, and
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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