Ferritin (Ft) impairment through (•)O2(-), H2O2, and (•)
OH production occurs in the cases of
ketoses,
diabetes mellitus,
acute intermittent porphyria and
tyrosinemia. In addition to (•)Trp and TyrO(•) radical production, ferrous
iron liberation and Ft synthesis stimulation, site-specific oxidation reactions are induced leading to toxic
iron accumulation in organs with high Ft content, for example, liver and brain. To elucidate the potential pathways to Ft recovery, repair of oxidative damage to horse spleen
apoferritin (apoFt) and Ft by
quercetin (QH) or
rutin (RH) was studied in the presence and absence of
oxygen. (•)Trp and TyrO(•) radicals were produced in pulse radiolysis through apoFt oxidation by (•)Br2(-) radicals. QH and RH bind to apoFt on eight sites with binding constants of ˜80,000 and ˜32,000 M(-1), respectively. In deaerated solutions, a repair of apoFt radicals is observed involving both bound and free
flavonoids. This repair occurs by a fast intra- and a slow inter-molecular electron transfer from bound and free
flavonoids, respectively. With QH, the rate constants are 10(4) s(-1) and 3.5 × 10(7) M(-1) s(-1) for the intra- and intermolecular repair reactions, respectively.
Oxygen does not interfere with repair of apoFt or Ft by bound QH but inhibits 90% of Ft repair by RH. These results taken together indicate that
flavonoid antioxidants may help alleviate Ft impairment in diseases involving an oxidative stress.