Iron/Heme Induces Oxidation And Nitration Injury: Effects Of Some Flavonoids

The deleterious of iron has been given much more attention in recent years. Many articles have focused on the oxidative injury induced by iron ion. Heme, the main form of iron existent in living body, has been reported to catalyze protein nitration. Flavonoid is a kind of natural antioxidant and there were many researches concerning its antioxidative effect and pharmacology. In this thesis, hemin/iron induced oxidation and nitration injury has been studied, the antioxidant effects of some flavonoids have also been discussed. The main results in this work are as follows:The effects of quercetin, catachin and baicalein on hemin-nitrite-H2O2 induced brain homogenate oxidation and nitration were studied in vivo. The results showed that hemin-nitrite-H2O2system could effectively induce brain homogenate protein nitration, lipid peroxidation, protein oxidation and thiol oxidation, quercetin, catachin and baicalein, could dose dependently inhibit hemin-nitrite-H2O2 system induced protein nitration and lipid peroxidation. However, these flavonoids showed marginal effect on hemin-nitrite-H2O2 system caused protein oxidation and thiol oxidation. The inhibiting order of flavonoids on protein nitration was similar to the scavenging order of flavonoids on free radicals.We also studied the effects of baicalin, baicalein and wogonin on hemin-nitrite-H2O2induced liver homogenate oxidation and nitration, and the protective effects on hemin-nitrite-H2O2 induced liver cell line L-O2 injury. Hemin-nitrite-H2O2 could effectively induce liver homogenate protein nitration, lipid peroxidation and thiol oxidation. Accordingly, hemin-nitrite-H2O2 could effectively induce L-O2 oxidative injury and protein nitration which could reduce the cell viability. Baicalein, baicalin and wogonin could dose dependently inhibite hemin-nitrite-H2O2 system induced protein nitration, whereas wogonin hardly inhibited lipid peroxidation. Baicalein, baicalin and wogonin could also protect L-O2 from the injury caused by hemin-nitrite-H2O2 system, however, only baicalein and baicalin showed a dose dependent manner.In iron overload mice model, it was found that iron overload could cause the increase of the ratio of liver weight to body weight, the content of liver iron, the concentration of MDA and SOD, the decrease of body weight gain, the total antioxidative ability, NOS and catalase. Baicalin supplementation could dose dependently alleviated above-mentioned abnormalities. The possible reason of baicalin reducing liver iron was to form baicalin-iron complex and excrete from body.