Selenocystine

  • 文章类型: Journal Article
    背景:为了防止超必需剂量硒的毒性,确定不良反应发生的剂量水平很重要。
    方法:我们确定了有关硒重复剂量的相关文献以及所报告终点的提取剂量描述符,除了遗传毒性/致癌性。
    结果:具有毒理学数据的硒形式是有机形式:硒代蛋氨酸,硒代半胱氨酸/硒代半胱氨酸;和无机物,包括亚硒酸盐(SeO32-),硒酸盐(SeO42-),硫化硒(SeS2),硒化物(Se2-)和硒纳米颗粒。人类硒中毒的临床症状包括刺耳的气味,脱发,指甲的变化。一项人体研究表明,每天摄入300µg硒持续5年,死亡率增加,等于观察到的最低不良反应水平(LOAEL)约4.3微克/千克体重/天。相应的未观察到的不良反应水平(NOAEL)为~2.9微克硒/千克体重/天。一项研究报告,2型糖尿病的风险增加后~2.9微克硒/千克体重/天,但其他类似剂量的研究未发现2型糖尿病的死亡率或发病率增加.动物研究中受影响体重的NOAELs为0.24-1.2mgSe/kgbw/天。动物中硒毒性的其他终点包括肝脏毒性,大鼠的NOAEL低至2µg/kgbw/天,以及胃肠道,心血管,和生殖毒性,NOAEL为0.6(胃肠道),0.08,和0.4(心血管)和≥0.04毫克硒/千克体重/天(生殖),分别。
    结论:描述硒毒性的剂量描述符低至2-3µgSe/kgbw/天。
    BACKGROUND: To protect from toxicity at supra-essential doses of selenium, it is important to determine dose levels at which adverse effects occur.
    METHODS: We identified relevant literature on the repeated dosage of selenium and extracted dose descriptors on reported endpoints, except on genotoxicity/carcinogenicity.
    RESULTS: Selenium forms with toxicological data were organic ones: selenomethionine, selenocystine/selenocysteine; and inorganic ones, including selenite (SeO32-), selenate (SeO42-), selenium sulphide (SeS2), selenide (Se2-) and selenium nanoparticles. Clinical signs of selenium toxicity in humans include a garlicky-smelling breath, hair loss, and nail changes. One human study showed increased mortality following daily ingestion of 300 µg Se per day for 5 years, equal to a lowest-observed-adverse-effect level (LOAEL) of ∼4.3 µg/kg bw/days. The corresponding no-observed-adverse-effect level (NOAEL) was ∼2.9 µg Se/kg bw/day. One study reported an increased risk of type 2 diabetes after ∼2.9 µg Se/kg bw/day, but other studies with similar doses found no increases in mortality or incidence of type 2 diabetes. NOAELs on affected body weight in animal studies were 0.24-1.2 mg Se/kg bw/day. Other endpoints of selenium toxicity in animals include hepatotoxicity with a NOAEL as low as 2 µg/kg bw/day in rats, as well as gastrointestinal, cardiovascular, and reproductive toxicities with NOAELs of 0.6 (gastrointestinal), 0.08, and 0.4 (cardiovascular) and ≥ 0.04 mg Se/kg bw/day (reproductive), respectively.
    CONCLUSIONS: Dose descriptors describing selenium toxicity were as low as 2-3 µg Se/kg bw/day.
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  • 文章类型: Journal Article
    背景:硒是传统上通过食物以有机形式或通过营养补充剂以无机形式摄入的微量元素,而硒被配制成纳米颗粒是一种公认的长效替代品。为了了解不同硒配方的生理和毒理学,重要的是要确定它们的硒含量是如何被吸收的,分布式,代谢和排泄;因此,我们回顾了他们口服暴露后的生物动力学。
    方法:我们检索并回顾了有关吸收的文献,分布,新陈代谢,和排泄口服暴露于不同形式的硒。
    结果:硒以有机形式(包含碳-硒化学键)和无机形式被吸收到人的血液中。许多研究的平均正常血液水平为139μg/L。有迹象表明,有机来源的硒比无机来源的硒更具生物可利用性。硒分布在全身,包括母乳。硒的消除主要涉及粪便和泌尿途径,而呼吸,唾液和头发是次要的贡献者。尿代谢产物包括三甲基硒离子,硒糖和硒-甲基硒酮。
    结论:硒被高度吸收,有机来源的硒比无机来源的硒更具生物可利用性。硒,正如预期的那样,作为一种必需的微量元素,分布在全身。硒被广泛代谢,在尿液和呼吸中都发现了各种排泄代谢物,而一些硒也通过粪便排出。
    BACKGROUND: Selenium is a trace element traditionally ingested either in its organic form via food or in its inorganic form through nutritional supplements, while selenium formulated as nanoparticles is a putative long-acting alternative. To understand the physiology and toxicology of the different selenium formulations, it is important to determine how their selenium content is absorbed, distributed, metabolised and excreted; therefore, we reviewed their biokinetics following oral exposure.
    METHODS: We retrieved and reviewed the literature on the absorption, distribution, metabolism, and excretion of oral exposure to different forms of selenium.
    RESULTS: Selenium in both the organic form (containing carbon to selenium chemical bonds) and the inorganic form is absorbed into the blood in humans. The mean normal blood level of many studies was 139 μg/L. There are indications that selenium from organic sources is more bioavailable than selenium from inorganic sources. Selenium is distributed throughout the body, including in breast milk. The elimination of selenium mainly involves the faecal and urinary pathways, whereas breath, saliva and hair are minor contributors. Urinary metabolites include trimethylselenium ions, selenosugars and Se-methylselenoneine.
    CONCLUSIONS: Selenium is absorbed to a high extent, and selenium from organic sources is more bioavailable than from inorganic sources. Selenium, as expected as an essential trace element, is distributed throughout the body. Selenium is extensively metabolised, and various excretion metabolites have been identified in both urine and breath, while some selenium is also excreted via faeces.
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