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首页> 外文期刊>Life sciences >Characteristics of selenazolidine prodrugs of selenocysteine: toxicity, selenium levels, and glutathione peroxidase induction in A/J mice.
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Characteristics of selenazolidine prodrugs of selenocysteine: toxicity, selenium levels, and glutathione peroxidase induction in A/J mice.

机译：硒代半胱氨酸的硒氮唑烷前药的特征：A / J小鼠的毒性，硒水平和谷胱甘肽过氧化物酶诱导。

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We have previously reported the synthesis and characterization of two new classes of selenazolidine-4(R)-carboxylic acids (2-oxo and 2-methyl-SCAs) (OSCA and MSCA, respectively), as well as the "parent" compound, selenazolidine-4(R)-carboxylic acid (SCA, selenaproline). These compounds were designed as prodrugs of L-selenocysteine with potential application in cancer chemoprevention or other clinical uses. We will be exploring the chemopreventive activity of the new compounds in the well-established A/J mouse model of tobacco-induced lung carcinogenesis. The objectives of the present study were to investigate several fundamental biochemical endpoints after selenazolidine administration compared with other selenium-containing agents. Groups of mice were fed either AIN-76A diet alone or the diet supplemented with the following selenium compounds (ppm Se): sodium selenite (5), L-selenomethionine (3.75), L-selenocystine (15), Se-methyl-L-selenocysteine (3), MSCA (5, 10, or 15), OSCA (5, 10, or 15), or SCA (5, 10, or 15). After 28 days of supplementation, toxicity of the selenazolidines was not evident, as measured by outward appearance and behavior, body and organ weight changes, and histological evaluation of liver and lung tissue. Select treatment groups showed significant increases in selenium levels in blood and tissues. Increased activity of selenium-dependent glutathione peroxidase (GPx) in blood and liver illustrated that the selenazolidines provided a source of biologically-available selenium.
机译：我们之前曾报道过两种新型硒代硒唑-4（R）-羧酸（分别为2-氧代和2-甲基-SCAs）（分别为OSCA和MSCA）以及“母体”化合物的合成和表征， selenazolidine-4（R）-羧酸（SCA，硒代脯氨酸）。这些化合物被设计为L-硒代半胱氨酸的前药，具有潜在的癌症化学预防或其他临床用途。我们将在成熟的烟草诱发的肺癌发生的A / J小鼠模型中探索新化合物的化学预防活性。本研究的目的是与其他含硒药物相比，研究硒氮唑烷给药后的几个基本生化终点。单独给小鼠饲喂AIN-76A饮食或补充以下硒化合物（ppm Se）的饮食：亚硒酸钠（5），L-硒代蛋氨酸（3.75），L-硒代胱氨酸（15），Se-甲基-L -硒代半胱氨酸（3），MSCA（5、10或15），OSCA（5、10或15）或SCA（5、10或15）。补充28天后，通过外观和行为，体重和器官重量变化以及肝和肺组织的组织学评估，硒代唑烷的毒性没有明显的变化。选择的治疗组显示血液和组织中硒水平显着增加。血液和肝脏中硒依赖性谷胱甘肽过氧化物酶（GPx）的活性增加表明硒代硒唑烷提供了生物可利用的硒来源。

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