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Selenium species-dependent toxicity, bioavailability and metabolic transformations in Caenorhabditis elegans†
Metallomics ( IF 2.9 ) Pub Date : 2018-05-14 00:00:00 , DOI: 10.1039/c8mt00066b
Isabelle Rohn 1, 2, 3, 4, 5 , Talke Anu Marschall 1, 2, 3, 4, 5 , Nina Kroepfl 6, 7, 8, 9, 10 , Kenneth Bendix Jensen 6, 7, 8, 9, 10 , Michael Aschner 11, 12, 13, 14, 15 , Simon Tuck 16, 17, 18, 19 , Doris Kuehnelt 6, 7, 8, 9, 10 , Tanja Schwerdtle 1, 2, 3, 4, 5 , Julia Bornhorst 1, 2, 3, 4, 5
Affiliation  

The essential micronutrient selenium (Se) is required for various systemic functions, but its beneficial range is narrow and overexposure may result in adverse health effects. Additionally, the chemical form of the ingested selenium contributes crucially to its health effects. While small Se species play a major role in Se metabolism, their toxicological effects, bioavailability and metabolic transformations following elevated uptake are poorly understood. Utilizing the tractable invertebrate Caenorhabditis elegans allowed for an alternative approach to study species-specific characteristics of organic and inorganic Se forms in vivo, revealing remarkable species-dependent differences in the toxicity and bioavailability of selenite, selenomethionine (SeMet) and Se-methylselenocysteine (MeSeCys). An inverse relationship was found between toxicity and bioavailability of the Se species, with the organic species displaying a higher bioavailability than the inorganic form, yet being less toxic. Quantitative Se speciation analysis with HPLC/mass spectrometry revealed a partial metabolism of SeMet and MeSeCys. In SeMet exposed worms, identified metabolites were Se-adenosylselenomethionine (AdoSeMet) and Se-adenosylselenohomocysteine (AdoSeHcy), while worms exposed to MeSeCys produced Se-methylselenoglutathione (MeSeGSH) and γ-glutamyl-MeSeCys (γ-Glu-MeSeCys). Moreover, the possible role of the sole selenoprotein in the nematode, thioredoxin reductase-1 (TrxR-1), was studied comparing wildtype and trxr-1 deletion mutants. Although a lower basal Se level was detected in trxr-1 mutants, Se toxicity and bioavailability following acute exposure was indistinguishable from wildtype worms. Altogether, the current study demonstrates the suitability of C. elegans as a model for Se species dependent toxicity and metabolism, while further research is needed to elucidate TrxR-1 function in the nematode.

中文翻译:

秀丽隐杆线虫的 硒物种依赖性毒性,生物利用度和代谢转化

各种系统功能都需要必需的微量营养素硒(Se),但其有益范围狭窄,过度接触可能会对健康造成不利影响。此外,摄入的硒的化学形式对其健康影响至关重要。虽然小的硒物种在硒的代谢中起主要作用,但人们对它们的毒理学作用,生物利用度和高吸收后的代谢转化的了解却很少。利用易处理的无脊椎动物秀丽隐杆线虫允许一种替代的方法来研究体内有机和无机硒形式的物种特异性特征,揭示了亚硒酸盐,硒代蛋氨酸(SeMet)和硒代甲基硒代半胱氨酸(MeSeCys)在毒性和生物利用度方面的显着物种依赖性差异。发现硒物种的毒性和生物利用度之间存在反比关系,有机物种显示的生物利用度高于无机形式,但毒性较低。用HPLC /质谱进行的定量Se形态分析表明,SeMet和MeSeCys有部分代谢。在暴露于SeMet的蠕虫中,鉴定出的代谢产物为Se-腺苷硒代蛋氨酸(AdoSeMet)和Se-腺苷硒同型半胱氨酸(AdoSeHcy),而暴露于MeSeCys的蠕虫则产生了Se-甲基硒代谷胱甘肽(MeSeGSH)和γ-谷氨酰-MeSeCys(γ)。而且,唯一的硒蛋白可能在线虫中发挥作用,硫氧还蛋白还原酶-1(TrxR-1)trxr-1缺失突变体。尽管在trxr-1突变体中检测到较低的基础硒水平,但是急性暴露后的硒毒性和生物利用度与野生型蠕虫没有区别。总而言之,当前的研究表明秀丽隐杆线虫适合作为依赖硒物种的毒性和代谢的模型,同时还需要进一步的研究来阐明线虫中的TrxR-1功能。
更新日期:2018-05-14
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