title: On the repair of oxidative damage to apoferritin: a model study with the flavonoids quercetin and rutin in aerated and deaerated solutions.
abstract: 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.
authors.affiliation: INSERM, U1088, 80054 Amiens cedex, France. morliere.patrice@chu-amiens.fr
authors.forename: P
authors.initials: P
authors.lastname: Morlière
authors.forename: J-C
authors.initials: JC
authors.lastname: Mazière
authors.forename: L K
authors.initials: LK
authors.lastname: Patterson
authors.forename: M-A
authors.initials: MA
authors.lastname: Conte
authors.forename: J-L
authors.initials: JL
authors.lastname: Dupas
authors.forename: J-P
authors.initials: JP
authors.lastname: Ducroix
authors.forename: P
authors.initials: P
authors.lastname: Filipe
authors.forename: R
authors.initials: R
authors.lastname: Santus
mesh_terms: D000388:Air; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001052:Apoferritins / Q000737:chemistry / Q000378:metabolism*; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D006736:Horses; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects*; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology*; D012431:Rutin / Q000737:chemistry / Q000494:pharmacology*; D012996:Solutions; D013154:Spleen / Q000737:chemistry
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D012996:Solutions; D012431:Rutin; D001052:Apoferritins; D011794:Quercetin