Effects of quercetin on hemoglobin-dependent redox reactions: relationship to iron-overload rat liver injury

Abstract

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 () 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.

Keywords::

• iron overload
• quercetin
• hemoglobin
• antioxidant
• pro-oxidant

Acknowledgments

The authors appreciate the financial support from the National Natural Science Foundation of China [grant numbers 31100608, 31260216, and 21162012], the Natural Science Foundation of Jiangxi province [grant number 20114BAB204013], the Education Department of Jiangxi Province [grant number GJJ12183], The Sponsored Program for Cultivating Youths of Outstanding Ability in Jiangxi Normal University, the Open Project Program of Key Laboratory of Functional Small Organic Molecule, Ministry of Education, Jiangxi Normal University [grant number KLFS-KF-201224], China Postdoctoral Science Foundation [grant number 2013M531557], and the Graduates' Innovation Fund of Jiangxi Province [grant number YC2012-S054].