Excess tissue iron content caused by iron overload or accumulation is often seen in individuals with hereditary hemochromatosis and those who require frequent blood transfusions. This excess tissue iron accumulation is toxic and may be associated with increases in myocardial apoptosis and the development of fibrosis. Wang et al. highlight new insights in the mechanism of iron overload and myocardial damage and the benefit of a new iron chelator agent, deferasirox. Using an iron-overloaded gerbil model, they found increased cardiac iron is associated with reduced activation of Akt, diminished phosphorylation of Bad, and an increased Bax/Bcl-2 ratio coupled with increased activation of the downstream caspase-9 and caspase-3, accompanied by cardiac fibrosis. These studies demonstrate that deferasirox administration is effective in attenuating iron overload-associated cardiac apoptosis and fibrosis and suggest that the activation of caspase-dependent signaling may play a role in the development of iron-induced cardiac apoptosis and fibrosis, and deferasirox, via a reduction in cardiac tissue iron levels, may be useful for decreasing the extent of iron-induced cardiac damage.
See article at J Pharmacol Exp Ther 2011, 336:56–63.
- Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics