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In this study we analyzed the data for combined RAR and RXR receptor levels as
well as variations in the RAR/RXR receptor ratio in response to different interventions.
ADR group animals exhibited a significant increase in the RAR/RXR receptor ratio due
to a higher increase in the RAR receptor levels then RXR receptors. The increase in RAR
receptors and RAR/R)G- receptor ratio may indicate an increased potential for retinoic
acid signaling, due to the factthatRAR receptors are obligate heterodimeric partners with
RXR receptors. In our in vitro studies the treatment with low doses of adriamycin to
ADR group myocytes resulted in an increased expression of RAR receptors. In vitro
adriamycin treatment did not cause any significant change in the total RXR receptor
levels but resulted in a significant increase in RAR/RXR ratio. These findings correlate
with our in vivo studies.
Although it is known that adriamycin administration causes apoptosis (Kumar et
al. 1999; Kumar et al. 2001), present study shows for the first time that adriamycin also
causes an increase in the RAR/RXR receptor ratio in ADR group hearts. This can be
seen to promote heterodimerization and such an adriamycin-induced disruption of
retinoic acid signaling process may lead to the occurrence of apoptosis and may be a
causative factor in the adriamycin-induced heart failure. The administration of probucol
to adriamycin treated animals decreased the RAR/RXR receptor ratio, this was mainly
due to a relatively higher increase in the RXR receptor levels. This change in ratio can be
seen to increase homodimenzationas well as retinoic acid signaling which can lead to the
protection against adriamycin-induced apoptosis. In vitro studies also showed that the
antioxidant trolox resulted in a decrease in the RARIRXR ratio in the ADR+TROL group
myocytes. Trolox has been shown to modulate adriamycin-induced apoptosis in this
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