Effects of quercetin on hemoglobin-dependent redox reactions: relationship to iron-overload rat liver injury.
Flavonoids have been widely reported to protect liver injury in iron-overload diseases, where the mechanism of this therapeutic action is dependent on their antioxidant effects, including free radical scavenging and metal-chelating. In this study, in contrast to the significant decrease in iron content, quercetin (Qu) from lower diet (0.3%, w/w) showed pro-oxidant ability on protein carbonyl formation and exhibited unobvious effect on iron-overload rat liver injury. Furthermore, the anti- and pro-oxidant activities of Qu on hemoglobin (Hb)-dependent redox reactions (i.e. the oxidative stability of Hb and its cytotoxic ferryl intermediate, Hb-induced protein oxidation) were investigated to illustrate the elevated protein oxidation in lower Qu-treated iron-overload rat. It was found that superoxide (O₂·⁻) and hydrogen peroxide (H₂O₂) were generated during the reaction between Qu and Hb. Qu, however, effectively reduced ferryl intermediate back to ferric Hb in a biphasic kinetic reaction. Moreover, Qu could significantly aggravate Hb-H₂O₂-induced protein oxidation at low concentrations and exhibit protective effects at high concentrations. Different from the classic antioxidant mechanisms of Qu, the dual effects on Hb redox reactions in vitro, therefore, may provide new insights into the physiological and pharmacological implications of Qu with iron-overload disease.
a Jiangxi Key Laboratory of Functional Organic Molecules, Jiangxi Science and Technology Normal University , Nanchang , 330013 , China.
Nai-Hao
NH
Lu
Chao
C
Chen
Ying-Jie
YJ
He
Rong
R
Tian
Qiang
Q
Xiao
Yi-Yuan
YY
Peng
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D006454:Hemoglobins / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000494:pharmacology
D000975:Antioxidants; D006454:Hemoglobins; D013481:Superoxides; D011794:Quercetin; D006861:Hydrogen Peroxide; D007501:Iron