d="sp0050">Iron chelator deferoxamine (DFO), LTCC blocker, TTCC blocker and DMT1 blocker were used to determine the roles of these channels regarding liver iron accumulation, apoptosis and iron regulatory protein expression in HT mice.
d="sp0055">TTCC and DMT1 blockers and DFO decreased liver iron and malondialdehyde (MDA) in HT mice indicating their antioxidant effects, whereas LTCC blocker produced no decrease in liver iron or MDA. However, only DFO decreased liver apoptosis through the reduced Bax/Bcl-2 ratio in wild type (WT) mice. The levels of iron regulatory hormone hepcidin were markedly higher in HT mice even before iron loading while ferroportin levels did not alter. Each of the pharmacological interventions increased ferroportin protein back to normal levels only in WT while HT mice showed no difference.
d="sp0060">Thalassemic mice have different hepcidin/ferroportin and apoptotic protein expression as a defense mechanism to iron-overload compared with those in WT mice. DFO was the most effective intervention in preventing liver apoptosis under iron-overload conditions in WT but did not have the same effect in HT mice.