Deferasirox decreases age-associated iron accumulation in the aging F344BN rat heart

Abstract

It is thought that aging in rats and humans is associated with increases in iron accumulation and these increases in iron may be associated with increased cellular apoptosis. Here we examine the relationship between cardiac iron levels and cardiomyocyte apoptosis in aged F344BN rats which were treated with an oral iron chelator (Deferasirox; 100mg/kg body. weight/day) for 6 months. Compared with 6- month controls, the levels of cardiac iron, cardiac apoptosis, FLC and DMT-1 were higher in 33-month hearts. Deferasirox treatment for six months decreased cardiac iron and this was associated with decreases in the number of apoptotic cardiac myocytes. Age-associated increases in cardiac apoptosis were coupled with alterations in the amount of Bcl-2 and Bax. Deferasirox treatment increased Bcl-2 expression and decreased Bad and activated caspase-12 expression. Taken together, these data suggest deferasirox may be effective in diminishing age-associated iron accumulation and cardiac apoptosis in the aging F344BN rat model