il\VOLVEMENT OF RETII\OIC ACID II{ - MSpace at the University of ...
il\VOLVEMENT OF RETII\OIC ACID II{ - MSpace at the University of ...
il\VOLVEMENT OF RETII\OIC ACID II{ - MSpace at the University of ...
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CONCLUSIONS<br />
It is now established th<strong>at</strong> <strong>the</strong> development <strong>of</strong> adriamycin-induced cardiomyop<strong>at</strong>þ is<br />
caused by an increase in oxid<strong>at</strong>ive stress- a finding confirmed in a present study. This<br />
increase in oxid<strong>at</strong>ive stress, results in specific changes in retinoic acid receptors such th<strong>at</strong><br />
<strong>the</strong>re is an increase in RARIRXR r<strong>at</strong>io, promoting <strong>the</strong> expression <strong>of</strong> proapoptotic gene,<br />
Bax and supporting <strong>the</strong> expression <strong>of</strong> proapoptotic protein Bcl-xl resulting in <strong>the</strong><br />
occurrence <strong>of</strong> apoptosis. Heterodimeriz<strong>at</strong>ion <strong>of</strong> RAR with RXR or RXR with PPAR ô<br />
and homodimeriz<strong>at</strong>ion <strong>of</strong> RXR appear to promote apoptosis. The usage <strong>of</strong> antioxidant<br />
probucol in vivo modul<strong>at</strong>es <strong>the</strong> oxid<strong>at</strong>ive stress as well as apoptosis. Retinoic acid<br />
(0.1pM) and trolox in vitro also showed similar effects. High doses <strong>of</strong> retinoic (1 pM),<br />
although acting as antioxidants, failed to prevent adriamycin-induced changes in retinoic<br />
acid receptor levels thus leading to apoptosis. This study indic<strong>at</strong>es th<strong>at</strong> retinoic acid<br />
receptors r<strong>at</strong>io (RAR/RXR) may play a significant medi<strong>at</strong>ing role in adriamycin-induced<br />
cardiomyop<strong>at</strong>hy. Future studies involving a precise predictable change in this r<strong>at</strong>io and<br />
consequent changes downstream will fur<strong>the</strong>r valid<strong>at</strong>e this suggestion.<br />
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