Design and Evaluation of Novel Selenium-Containing Antioxidant

新型含硒抗氧化剂的设计与评价

• 批准号: 07455352
• 负责人: NIKI Etsuo
• 金额: $ 3.9万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07455352/
• 关键词: antioxidant; lipid peroxidation; free radical; oxidative damage; selenium; peroxide; ebselen; エブセレン

There is now increasing evidence which shows that the free-radical mediated oxidations proceed in vivo as in plastics rubber and lipids and that they play a causative role in the progression of various diseases, cancer and aging. As a consequence, the inhibition of such oxidations and development of novel potent antioxidants have received much attention. The present research has been carried out aiming at developing a novel selenium-containing antioxidant and evaluating its antioxidant potency. Ebselen, 2-phenyl-1,2-benzisoselenazol-3 (2H) -one, was chosen as a candidate and its antioxidant action and activity were studied. It was confirmed that ebselen did not act as a radical scavenger nor did it reduce vitamin E radical to regenerate vitamin E.Ebselen reduced hydroperoxides rapidly to corresponding alcohol and thereby inhibited the metal-catalyzed oxidations of lipids and low density lipoproteins. Furthermore, it was found that ebselen completely inhibited the lipid oxidation induce by lipoxygenase. Ebselen also exerted potent antioxidant activity against lipid peroxidation induced by peroxynitrite. It was concluded that ebselen is a potent antioxidant against oxidations induced by metal ions and peroxynitrite.

现在有越来越多的证据表明，自由基介导的氧化在体内进行，如在塑料橡胶和脂质中，并且它们在各种疾病、癌症和衰老的进展中起着致病作用。因此，抑制这种氧化和开发新的有效的抗氧化剂受到了广泛的关注。本研究旨在开发一种新型的含硒抗氧化剂，并对其抗氧化能力进行评价。Ebselen，2-苯基-1，2-苯并异硒唑-3（2 H）-酮，被选为抗氧化剂候选物，并对其抗氧化作用和活性进行了研究。结果表明，依布硒啉既不作为自由基清除剂，也不还原维生素E自由基而再生维生素E。依布硒啉能迅速将过氧化氢还原为相应的醇，从而抑制金属催化的脂质和低密度脂蛋白的氧化。此外，还发现依布硒啉完全抑制脂氧合酶诱导的脂质氧化。依布硒啉还对过氧亚硝酸盐诱导的脂质过氧化产生有效的抗氧化活性。由此得出结论，依布硒啉是一种有效的抗氧化剂，对金属离子和过氧亚硝酸盐诱导的氧化。

项目成果

T.Urakami, A.Tanaka, K.Yamaguchi, T.Tsuji, and E.Niki: "Synthesis of esters of coenzyme PQQ and IPQ,and stimulation of nerve growth factor production." BioFactors. 5. 139-146 (1996)

T.Urakami、A.Tanaka、K.Yamaguchi、T.Tsuji 和 E.Niki：“辅酶 PQQ 和 IPQ 酯的合成以及神经生长因子产生的刺激。”

Y.Nagata, Y.Yamamoto, and E.Niki: "Reaction of phosphatidylcholin hydroperoxide inhuman plasma : The role of peroxidase and lecithin : Cholesterol acyltrandferase." Arch.Biochem.Biophys.329. 24-30 (1996)

Y.Nagata、Y.Yamamoto 和 E.Niki：“人血浆中磷脂酰胆碱氢过氧化物的反应：过氧化物酶和卵磷脂的作用：胆固醇酰基转移酶”。

N.Noguchi, H.Sakai, Y.Kato, J.Tsuchiya, Y.Yamamoto, E.Niki, and H.Horikoshi: "Inhibition of oxidation low density lipoprotein by troglitazone." Atherosclerosis. 123. 227-234 (1996)

N.Noguchi、H.Sakai、Y.Kato、J.Tsuchiya、Y.Yamamoto、E.Niki 和 H.Horikoshi：“曲格列酮对低密度脂蛋白氧化的抑制作用。”

K.Hayashi,E.Niki,et al.: "Action of nitric oxide as an antioxidant against oxidation of soybean phosphatidylcholine liposomal membranes." FEBS Lett.370. 37-40 (1995)

K.Hayashi、E.Niki 等人：“一氧化氮作为抗氧化剂对抗大豆磷脂酰胆碱脂质体膜氧化的作用。”

H.Yasuda,E.Niki,et al.: "Hepatic damage induced by perfusion of radical generating azo compound and its inhibition by vitamin E." Chem.Biol.Inter.97. 11-23 (1995)

H.Yasuda,E.Niki,et al.：“自由基生成偶氮化合物灌注引起的肝损伤及其维生素 E 的抑制作用。”