The Effects Of Organic And Inorganic Molecules On Hemoglobin-dependent Redox Reaction

Evidence to support the role of heme proteins as major inducers of oxidativedamage is increasingly present. Antioxidants have been widely used to ameliorateoxidative damage in vivo and in vitro, where the mechanism of this therapeutic actionwas usually dependent on their anti-oxidant effects. In this study, we chose two typesof antioxidants, organic and inorganic molecules, to study their efficiencies onhemoglobin-induced protein oxidative damage. The main research contents includethe following two aspects:（1）The effects of flavonoids on hemoglobin-dependent redox reactionIn this chapter, we investigated the influence of rutin（quercetin-3-rhamnosylglucoside）, which is more abundant than quercetin in plantfoods and medicinal herbs, on hemoglobin-induced protein oxidative damage. It wasfound that rutin had the capacities to act as a free radical scavenger and reducingagent to remove cytotoxic ferryl hemoglobin, demonstrating apparent anti-oxidantactivities. However, rutin had the ability to rapidly trigger hemoglobin oxidationthrough producing additional reactive species, such as hydrogen peroxide （H₂O₂）, andsubsequently significantly promoted hemoglobin-induced protein oxidation. On theother hand, rutin could significantly aggravate hemoglobin-H₂O₂-protein oxidation atlow concentrations and exhibit protective effects at high concentrations. Comparedwith quercetin, rutin with higher ferryl species reducing ability exhibited moreprotective effect on H₂O₂-induced hemoglobin oxidation. Meanwhile, quercetin withstronger free radical scavenging had stronger pro-oxidant activities in triggerringhemoglobin oxidation and enhancing hemoglobin-induced protein oxidation.（2）The effects of nitrite on hemoglobin-dependent redox reactionNitrite （NO₂^-） is one of the major end products of NO metabolism. Although thebiological significanceof heme/NO₂^--mediated protein tyrosine nitration is a subjectof great interest, the important roles of NO₂^-on hemoglobin-dependent redox reactionhave been greatly underestimated. In this chapter, we investigated the influence ofNO₂^-on hemoglobin-dependent oxidative damage. It was found that NO₂^-had thecapacity to act as a reducing agent to remove cytotoxic ferryl hemoglobin andefficiently inhibit ferryl hemoglobin-induced protein carbonyl formation,demonstrating its anti-oxidant activity. However, the presence of NO₂^-surprisinglyexerted pro-oxidant effect on hemoglobin-H₂O₂-induced protein oxidation at lowconcentrations, which was probably due to the ability of NO₂^-to reduce ferryl Hb tothe ferric state, thus, accelerating the turnover of the pseudoperoxidase.