il\VOLVEMENT OF RETII\OIC ACID II{ - MSpace at the University of ...

treated (ADR), trolox treated (TROL), combined adriamycin and trolox treated
(ADR+TROL), 0.1 ¡rM retinoic acid treated (O.iRA), 0.1 pM retinoic acid and
adriamycin treated (0.1R4+ADR), 1 pM retinoic acid treated ( 1RA) and i pM retinoic
acid and adriamycin treated (lRA+ADR).
The occurrence of adriamycin-induced heart failure in observed animals was
confirmed by clinical, hemodlmamic and echocardiographic data. The occurrence of
adriamycin-induced heart failure \Ã/as accompanied by: dyspnea; a decrease in the left
ventricular systolic pressure (LVSP); decrease in cardiac output and left ventricular mass;
and an increase in the left ventricular end-diastolic pressure (LVEDP). All these changes
were prevented by the administration of antioxidant probucol. The administration of
adriamycin, in vitro, was shown to cause an increase in oxidative stress which was
prevented by the administration of water soluble antioxidant trolox and low and high
doses of retinoic acid.
Adriamycin-induced increase in the oxidative stress was found to cause an
increase in the RAR/RXR receptor ratio which effected the expression of proapoptotic
(Bax) and antiapoptotic proteins (Bcl-xl), thus resulting in an increase in the BaxlBcl-xl
ratio. The increase in Bax/Bcl-xl ratio led to an increase in apoptosis in cardiac myocytes.
The treatment with antioxidants probucol (in vivo) and trolox (in vitro) caused a decrease
in RAR/RXR ratio resulting in a decrease in the Bax/Bcl-xl ratio, thus preventing the
occulrence of adriamycin-induced apoptosis. The administration of low doses of retinoic
acid (0.1¡rM) also caused a decrease in the RAR/RXR receptor ratio resulting in the
prevention of adriamycin-induced apoptosis. The high doses of retinoic acid, although
reduced oxidative stress but potentiated adriamycin-induced increase in the RAR/RXR