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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<strong>II</strong>.In Vitro Studies<br />
Calcium tolerant cardiomyocytes were isol<strong>at</strong>ed as described in <strong>the</strong> methods<br />
section. Isol<strong>at</strong>ed myocytes were exposed to different concentr<strong>at</strong>ions <strong>of</strong> adriamycin to<br />
examine <strong>the</strong> effects <strong>of</strong> this drug on different parameters described below. The effects <strong>of</strong><br />
retinoic acid and trolox on <strong>the</strong> adriamycin-induced changes were also studied.<br />
ILa. Total RAR and total RXR recentor levels<br />
The effects <strong>of</strong> adriamycin (4, 8 and 10 pM) on retinoic acid receptor dynamics<br />
were studied in <strong>the</strong> presence <strong>of</strong> two different concentr<strong>at</strong>ions <strong>of</strong> retinoic acid (0.1 and 1<br />
¡rM) and antioxidant trolox (20 pM). In adriamycin tre<strong>at</strong>ed groups, myocytes were<br />
incub<strong>at</strong>ed with three different concentr<strong>at</strong>ion <strong>of</strong> adriamycin (4, 8 and 10 pM) for a period<br />
<strong>of</strong> 8 hrs. These doses were selected on <strong>the</strong> basis <strong>of</strong> our preliminary d<strong>at</strong>a in which a 10 ¡rM<br />
concentr<strong>at</strong>ion <strong>of</strong> adriamycin was found to be <strong>the</strong> maximum dose toler<strong>at</strong>ed when myocytes<br />
begin to lift from <strong>the</strong> bottom <strong>of</strong> <strong>the</strong> distq while <strong>at</strong> I UM concentr<strong>at</strong>ion <strong>the</strong>re was hardly<br />
any observable effect. Trolox was administered I hour prior to administr<strong>at</strong>ion <strong>of</strong><br />
adriamycin and 8 h¡s concomitantly with adriamycin. The same administr<strong>at</strong>ion protocol<br />
was used for <strong>the</strong> cells tre<strong>at</strong>ed with I FM and 10 pM <strong>of</strong> retinoic acid. The results for each<br />
goup were compared with <strong>the</strong> control group which was set <strong>at</strong> l00Yo and this d<strong>at</strong>a was<br />
shown in figures 16-18.<br />
92