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非人类灵长类动物中L-硒代蛋氨酸形式的硒的吸收、分布和排泄

Absorption, distribution and elimination of selenium as L-selenomethionine in non-human primates.

作者信息

Willhite C C, Hawkes W C, Omaye S T, Choy W N, Cox D N, Cukierski M J

机构信息

Department of Toxic Substances Control, California EPA, Berkeley 94710.

出版信息

Food Chem Toxicol. 1992 Nov;30(11):903-13. doi: 10.1016/0278-6915(92)90174-j.

Abstract

20 adult female macaques (Macaca fascicularis) were given oral doses of L-selenomethionine (L-SeMet) equivalent to 0, 25, 150, 300 and 600 micrograms selenium (Se)/kg body weight, and plasma, erythrocyte, hair, faecal and urine Se concentrations were determined. The macaques were scheduled for 30 daily oral doses of L-SeMet, but systemic toxicity necessitated dose reduction in several animals; two macaques given 600 micrograms Se/kg body weight/day for 10-15 days died, and the concentration of Se in their tissues was determined and compared with Se concentrations in tissues collected from one untreated animal. Circulating and urinary Se concentrations in control macaques were within the normal human ranges. Plasma, erythrocyte, hair and urinary Se concentrations were generally dependent on the dose of L-SeMet administered. Plasma Se reflected more immediately exposure to L-SeMet, whereas erythrocyte Se concentrations increased and decreased more slowly. In some cases, erythrocyte Se was still increasing or showed a plateau after L-SeMet treatment was discontinued. Plasma Se concentrations of 6.7-7.3 ppm were observed in the two animals that died due to acute toxicity to L-SeMet. Neither plasma nor erythrocyte GPx activity was influenced by a single L-SeMet dose, but an increase in erythrocyte GPx activity occurred with continuous exposure. Total tissue Se increased 13-28-fold in macaques given 600 micrograms Se/kg body weight/day for 10-15 days, with the liver and kidneys containing the the highest Se concentrations.

摘要

给20只成年雌性猕猴(食蟹猴)口服相当于0、25、150、300和600微克硒(Se)/千克体重的L-硒代蛋氨酸(L-SeMet),并测定血浆、红细胞、毛发、粪便和尿液中的硒浓度。这些猕猴计划每天口服30次L-SeMet,但由于全身毒性,几只动物需要减少剂量;两只每天给予600微克硒/千克体重、持续10 - 15天的猕猴死亡,并测定了它们组织中的硒浓度,并与从未经处理的一只动物收集的组织中的硒浓度进行比较。对照猕猴的循环和尿液硒浓度在正常人类范围内。血浆、红细胞、毛发和尿液中的硒浓度通常取决于所给予的L-SeMet剂量。血浆硒更直接地反映了对L-SeMet的暴露情况,而红细胞硒浓度的增加和降低则较为缓慢。在某些情况下,停止L-SeMet治疗后,红细胞硒仍在增加或呈现平台期。因对L-SeMet急性毒性死亡的两只动物的血浆硒浓度为6.7 - 7.3 ppm。单次L-SeMet剂量对血浆或红细胞谷胱甘肽过氧化物酶(GPx)活性均无影响,但持续暴露会导致红细胞GPx活性增加。每天给予600微克硒/千克体重、持续10 - 15天的猕猴,其组织总硒增加了13 - 28倍,肝脏和肾脏中的硒浓度最高。

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