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study as well as in others (Kumar et aI. 1999). This data further supports the hypothesis
that the administration of antioxidants protects against adriamycin-induced oxidative
stress as well as damage to retinoic acid receptors and prevents the occurrence of
apoptosis.
In vitro studies using two concentrations of RA (0.1 and lpM) revealed an
interesting finding. At both concentrations, RA decreased oxidative stress. However, it
was only at low concentrations of RA that I saw a decrease in RAR/RXR ratio as well as
a decrease on apoptosis. Treatment with 1 pM RA, on the other hand, despite a decrease
in oxidative stress, was found to increase the RAR receptor expression as well as
RAR/RXR ratio and increased apoptosis Clearly in presence of high concentration of
RA, there is a dissociation between oxidative stress and increased apoptosis. It is likely
due to some direct effect of RA on its receptors. kr this regard, retinoic acid induced upregulation
of its own receptors as has been reported by others (Napoli 1996; Napoli 1999;
Petkovich et al. 1987).
V. PPRA ô studies
The role of PPAR receptors in cardiovâscular system is still unknown. However, a
number of studies indicate that PPAR receptors may be involved in the regulation of a
number of life essential processes such as energy utilization in the heart, glucose and
fatty acid metabolism, oxidative stress, apoptosis and insulin sensitivify (Barger and
Kelly 2000; Diep and Schiffrin Z}}L;Fruchart et al. 2001; Guerre-Millo et al. 2001)' The
PPAR-ô receptor , which is found predominantly in the heart, plays a significant role in
the regulation of oxidative stress and apoptosis, while its natural ligands are still
unknown (Cutler et al.2003; O'Brien et al.2005; Spiegelman and Flier 1996)' A number
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