Thesis (PH.D.) - Cairo University - Faculty Of Pharmacy - Department Of Biochemistry

The use of adriamycin (ADR) as potent antitumor agent is seriously limited by development of its cardiotoxicity The present work was undertaken to study the protective effect of probucol (PROB) as an antioxidant and deferoxamine (DFO) as iron chelator against the cardiotoxic action of adriamycin Repeated administration of adriamycin caused cardiotoxicity manifested biochemically by reduction of cellular energy level as indicated by inhibition of fatty acids oxidation , low ATP / ADP ratio and diminish Na+ , K+ATPase activity Moreover , state of increased oxidative stress was also manifested by increased MDA and decreased antioxidants (GSH and GSHPx) in the heart This state is augmented by increased XO / XD ratio as a potential generator of free radical in the heart Pretreatment with PROB or DFO caused a partial recovery of most of biochemical changes caused by ADR However , combined therapy of PROB and DFO provided an excellent protection against ADR cardiotoxicity where normalization most biochemical parameters has been achieved Beside the beneficial effects of the protective agents , they did not affect the antitumour properties of ADR

Issued also as CD