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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tre<strong>at</strong>ed (ADR), trolox tre<strong>at</strong>ed (TROL), combined adriamycin and trolox tre<strong>at</strong>ed<br />
(ADR+TROL), 0.1 ¡rM retinoic acid tre<strong>at</strong>ed (O.iRA), 0.1 pM retinoic acid and<br />
adriamycin tre<strong>at</strong>ed (0.1R4+ADR), 1 pM retinoic acid tre<strong>at</strong>ed ( 1RA) and i pM retinoic<br />
acid and adriamycin tre<strong>at</strong>ed (lRA+ADR).<br />
The occurrence <strong>of</strong> adriamycin-induced heart failure in observed animals was<br />
confirmed by clinical, hemodlmamic and echocardiographic d<strong>at</strong>a. The occurrence <strong>of</strong><br />
adriamycin-induced heart failure \Ã/as accompanied by: dyspnea; a decrease in <strong>the</strong> left<br />
ventricular systolic pressure (LVSP); decrease in cardiac output and left ventricular mass;<br />
and an increase in <strong>the</strong> left ventricular end-diastolic pressure (LVEDP). All <strong>the</strong>se changes<br />
were prevented by <strong>the</strong> administr<strong>at</strong>ion <strong>of</strong> antioxidant probucol. The administr<strong>at</strong>ion <strong>of</strong><br />
adriamycin, in vitro, was shown to cause an increase in oxid<strong>at</strong>ive stress which was<br />
prevented by <strong>the</strong> administr<strong>at</strong>ion <strong>of</strong> w<strong>at</strong>er soluble antioxidant trolox and low and high<br />
doses <strong>of</strong> retinoic acid.<br />
Adriamycin-induced increase in <strong>the</strong> oxid<strong>at</strong>ive stress was found to cause an<br />
increase in <strong>the</strong> RAR/RXR receptor r<strong>at</strong>io which effected <strong>the</strong> expression <strong>of</strong> proapoptotic<br />
(Bax) and antiapoptotic proteins (Bcl-xl), thus resulting in an increase in <strong>the</strong> BaxlBcl-xl<br />
r<strong>at</strong>io. The increase in Bax/Bcl-xl r<strong>at</strong>io led to an increase in apoptosis in cardiac myocytes.<br />
The tre<strong>at</strong>ment with antioxidants probucol (in vivo) and trolox (in vitro) caused a decrease<br />
in RAR/RXR r<strong>at</strong>io resulting in a decrease in <strong>the</strong> Bax/Bcl-xl r<strong>at</strong>io, thus preventing <strong>the</strong><br />
occulrence <strong>of</strong> adriamycin-induced apoptosis. The administr<strong>at</strong>ion <strong>of</strong> low doses <strong>of</strong> retinoic<br />
acid (0.1¡rM) also caused a decrease in <strong>the</strong> RAR/RXR receptor r<strong>at</strong>io resulting in <strong>the</strong><br />
prevention <strong>of</strong> adriamycin-induced apoptosis. The high doses <strong>of</strong> retinoic acid, although<br />
reduced oxid<strong>at</strong>ive stress but potenti<strong>at</strong>ed adriamycin-induced increase in <strong>the</strong> RAR/RXR