罗望子多糖硒酸酯的制备及表征

目的:合成罗望子多糖硒酸酯,并表征其结构特征。方法:在HNO3-BaCl2催化作用下,利用亚硒酸钠合成罗望子多糖硒酸酯,以硒含量为指标对合成工艺进行优选,采用红外吸收光谱、热重分析、GPC等方法对合成产物进行表征。结果:罗望子多糖硒酸酯最佳合成条件为硝酸浓度为0.5%,反应温度80℃,反应时间14 h,此条件下产物硒含量约为22 mg.g-1,结论:合成产物中硒以Se=O的形式存在,且与纯多糖比较,多糖硒酸酯热稳定性和相对分子质量稍有降低,可能是由于酸性反应体系下罗望子多糖稍有降解,同时引入的亚硒酸基对分子结构产生了影响。     

硒化壳聚糖和亚硒酸钠抗K562细胞的实验研究

应用MTT比色分析法比较研究有机硒化物-硒化壳聚糖和无机硒化物亚硒酸钠对白血病K562细胞的作用。结果表明：两种硒在体外实验浓度范围内均对K562细胞的增殖具有显著的抑制作用，并有剂量反应关系：硒化壳聚糖的抗白血病效应明显高于含同样硒量的亚硒酸钠，约为其3倍，有机硒比无机硒具有更高的抗白血病活性。     

正交设计研究多贝斯和硒的抗血小板血栓作用

目的　研究多贝斯与硒 2种药物联合应用抗血小板血栓形成的作用 ,寻求合用的最佳组方剂量。方法　采用 2因素 3水平 [L9(34 ) ]的正交设计 ,观察药物对大鼠动 -静脉旁路血小板血栓形成的影响 ,用 SPSS软件统计实验结果。结果　在抑制血栓形成方面 ,多贝斯的作用强于亚硒酸钠 ;多贝斯的低剂量 (6 3mg.kg-1)作用最强 ;亚硒酸钠的中剂量 (0 .1mg.kg-1)作用最强。最佳搭配应为多贝斯低剂量加亚硒酸钠中剂量。结论　多贝斯与亚硒酸钠的交互作用有统计学意义 ,两药合用在抗血栓形成中为拮抗作用 ,故不宜合用     

玉米须多糖提取工艺条件的优化

目的研究提取玉米须粗多糖的最佳工艺条件。方法选用煎煮次数、煎煮时间、加水倍数及乙醇浓度作为考察因素,以提取液中多糖含量为考察指标,通过L9(34)正交表试验,筛选玉米须多糖的提取工艺条件。结果玉米须多糖提取最佳条件为煎煮3次,每次1 h,加水14倍,乙醇浓度为60%。结论可以通过正交试验优化提取玉米须多糖的最佳工艺条件。     

亚硒酸钠诱导人急性早幼粒细胞白血病细胞株NB4细胞氧化应激和细胞凋亡

目的研究亚硒酸钠诱导NB4细胞的氧化应激和细胞凋亡。方法MTT比色法检测亚硒酸钠对NB4细胞的生长抑制;用形态学、DNA琼脂糖电泳和流式细胞术研究亚硒酸钠诱导NB4细胞凋亡的作用;用化学发光法和比色法研究亚硒酸钠对NB4细胞内氧化应激的影响。 结果亚硒酸钠可以时间和剂量依赖性地抑制NB4细胞生长和诱导NB4细胞凋亡。亚硒酸钠(≥5 μmol·L^-1)提高了NB4细胞内ROS水平,同时伴有细胞内还原型谷胱甘肽含量下降,而抗氧化剂NAC可抑制亚硒酸钠诱导的NB4细胞氧化应激和细胞凋亡。结论亚硒酸钠诱导NB4细胞氧化应激可能是其诱导NB4细胞凋亡的重要机理。     

老年大鼠的慢性硒中毒

目的　探讨老年大鼠对硒的耐受剂量 ,并比较有机硒 (富硒平菇 )与亚硒酸钠的优劣。方法　在正常饲料的基础上 ,分别加亚硒酸钠、普通平菇干粉、富硒平菇干粉配成含硒量为 0 9、0 3、0 2、0 172mg/kg混合饲料 ,对 18个月龄的Wistar大鼠进行实验 ,实验期 10 2d。观察实验前后体重变化、生存时间、谷胱甘肽过氧化物酶(GSH PX)活性、血红蛋白 (Hb)含量、丙氨酸转氨酶 (ALT)活性、尿素氮 (BUN)含量以及脂质过氧化物 (LPO)含量和超氧化物歧化酶 (SOD)活性。结果　①亚硒酸钠 0 9mg/kg组GSH PX活性随喂养时间延长活性降低、富硒平菇 0 9、0 3mg/kg两组均随时间延长而活性增加。②雄、雌性大鼠在实验前后体重有显著变化 ,雄性减重、雌性增重。③富硒平菇和亚硒酸钠 0 9mg/kg两组生存时间均有降低。④亚硒酸钠 0 9mg/kg组Hb含量降低、ALT活性增高。⑤普通平菇组Hb含量有所增高。⑥富硒平菇 0 3mg/kg组LPO含量降低。结论　亚硒酸钠 0 9mg/kg饲料长时间补充对老年鼠有毒害作用。而适量硒的补充 ,特别是富硒平菇适量硒剂量的补充则有益     

富硒平菇和亚硒酸钠对老年大鼠有关指标的影响

目的　探讨有关硒对老年大鼠 (18月龄 )凝血和纤溶功能有关指标的影响以及富硒平菇和亚硒酸钠对老年鼠合适的补充剂量 ,并比较富硒平菇和亚硒酸钠的优劣。方法　对 18月龄老年鼠进行实验 ,实验期12 3d ,分别观察添加亚硒酸钠或富硒平菇干粉的饲料 (含硒量为 0 2、0 2 5、0 4、0 6mg/kg)对血浆血栓素、前列环素、D 二聚体 (DD)、谷胱甘肽过氧化酶 (GSH PX)、超氧化物歧化酶 (SOD)、脂质过氧化物 (LPO)以及丙氨酸转氨酶(ALT)和实验前后体重变化的差异。结果　适量硒 0 2mg/kg饲料 ,补硒 0 4mg/kg饲料 ,对于老年大鼠前列环素 (PGI2 )含量的增高有促进作用 ,对血栓素A2 (TXA2 )有降低作用 ,对于PGI2 /TXA2 的比值和GSH PX活性的提高及LPO的降低均有促进作用。 0 6mg/kg饲料不能降低PGI2 /TXA2 的比值 ,并能造成D D含量增高和ALT活性有所提高 ,0 6mg/kg饲料组亚硒酸钠还能引起老年鼠体重下降 ,结果还提示富硒平菇优于亚硒酸钠。 结论　补硒应当慎重。     

胰岛素和亚硒酸钠最佳配比组方研究

目的 确定普通胰岛素与亚硒酸钠降血糖作用的最佳组方配比.方法 采用小剂量链脲佐菌素腹腔注射联合高糖高脂饲养的大鼠模型,以血糖降低百分率为考察指标,根据权重配方法设不同配比组方6组,分析结果得出最佳理论配比,并进一步做确证性试验考察二者的相互关系.结果 胰岛素与亚硒酸钠对血糖的控制为协同作用,二者比例为1 U:5μg时可显著降低血糖.结论 胰岛素和亚硒酸钠的最佳配比为1 U:5μg.     

富硒维酶素的制备和抗瘤活性研究

目的研究富硒维酶素的制备及其所含成分的测定方法和抗肿瘤活性。方法用棉病囊菌经固体发酵利用亚硒酸钠制备富硒维酶素。测定富硒维酶素含硒量和其他成分 ,并与维酶素比较。初步进行对小鼠的抗肿瘤活性试验。结果制备的富硒维酶素含硒量比维酶素高 0 .0 2 6 %。与维酶素比较对几种肿瘤具有不同程度的抗肿瘤作用 ,特别对Lewis肺癌的抑瘤作用达到 37.8%～ 5 1.0 %。结论棉病囊菌可以利用亚硒酸钠制备富硒维酶素 ,后者对Lewis肺癌的抑瘤率比维酶素提高了大约 2 .5倍。     

荧光分光光度法测定硒多糖胶囊中的硒含量

目的 测定硒多糖胶囊中硒的舍量。方法 采用2，3-二氨基萘荧光分析法测定硒的含量。结果 平均回收率为98．2%。结论 此法特异性强，精密度高，快速而简便。     

Studies on selenium-related compounds VI. Biosynthesis of dimethyl selenide in rat liver after oral administration of sodium selenate

Experiments were made to obtain data on the biological action of selenium in order to establish a standard for water quality for public water supply. Biosynthesis of dimethyl selenide in rat liver after oral administration of Na₂SeO₄ was investigated and the volatile selenium formed was identified. The study showed that dimethyl selenide, as a respiratory metabolite, was probably formed in the rat liver. Differences were noted as to dimethyl selenide formation from sodium selenite and sodium selenate in vitro. The test of single oral administration of sodium selenate indicated that dimethyl selenide formation increased progressively up to about 6 mg/kg and then reached a plateau at this dose. The increased accumulation of selenium in the liver after continuous oral administration was found to stimulate the methylation of selenium to dimethyl selenide. When sodium selenate was orally administered to rats, (CH₃)₂Se was found by TLC, GLC, and GC-mass spectrometry.     

The stimulation and inhibition of the exhalation of volatile selenium

Administration of methylmercury (1.5-24 mumol kg-1; s.c.) to female rats simultaneously with Na2 75SO3 (0.25 or 24 mumol kg-1; s.c.) causes a dose-dependent increase in the exhalation of dimethylselenide. At the low selenite dose level, exhalation of 75Se over a 24 hr period is about fourfold greater after treatment with 24 mumol kg-1 methylmercury than that (approximately 0.75% of the dose) in the controls, but excretion by other routes (urine, faeces) and the liver and kidney contents of 75Se are not affected significantly. At the higher selenite dose level (24 mumol kg-1) exhalation of 75Se is correlated with the log dose of methylmercury. The faecal and urinary excretion remains essentially unaffected, and in rats treated with 24 mumol kg-1 methylmercury the 75Se contents of the liver, kidneys and blood are reduced by 78%, 86% and 18% respectively. The effects of the alkylmercurial are not specific since, at this selenite dose level, ethylmercury increases the exhalation and decreases the liver and kidney contents of 75Se approximately to the same extent as an equimolar dose of methylmercury. In methylmercury-treated and control animals dosed with 24 mumol kg-1 Na 75SeO3 the exhalation of 75Se is inhibited to the same extent by periodate-oxidized adenosine (PAD; 15 mumol kg-1, i.p.) in the first 6 hr. Later inhibition is less pronounced in methylmercury-treated rats. Under these conditions PAD has little effect on the renal content, but increases the hepatic content of 75Se. It seems, therefore, that the methylation of selenite occurs mainly in the liver and in both control and methylmercury-treated animals, S-adenosylmethionine is the major methyl donor. It is possible that methylmercury does not affect directly the methylation enzyme system but, by competition for protein sulphydryl groups, increases the availability of the intermediary selenide anion.     

Comparative oral dose toxicokinetics of sodium selenite and selenomethionine

Selenium (Se) poisoning by different forms of Se occurs in the United States. However, the toxicokinetics of different selenocompounds after oral ingestion is not well documented. In this study the toxicokinetics of Se absorption, distribution and elimination were determined in serum and whole blood of lambs that were orally dosed with increasing doses of Se as sodium selenite (inorganic Se) or selenomethionine (SeMet, organic Se). Thirty‐two lambs were randomly assigned to eight treatment groups, with four animals per group. Se was administered at 1, 2 or 3 mg kg⁻¹ body weight, as either sodium selenite or SeMet with proper control groups. Blood and serum were collected at predetermined time points for 7 days post‐dosing. Resulting Se concentrations in both serum and whole blood from SeMet treatment groups were significantly greater than those given equimolar doses of Se as sodium selenite. Se concentrations in serum and whole blood of lambs dosed with SeMet peaked at significantly greater concentrations when compared with lambs dosed with equimolar doses of sodium selenite. Based on the serum and whole blood kinetics, the rate of Se absorption was greater for SeMet than for sodium selenite although rates of absorption for both Se forms decreased with increasing dose. The rates of Se elimination increased with dose. These results demonstrate that SeMet has a greater absorption rate and a similar retention time resulting in a greater area under the curve and thus bioavailability than sodium selenite, which must be considered in both overdose and nutritional exposures. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.     

Embryotoxic and teratogenic effects of selenium in the diet of mallards

Mallards (Anas platyrhynchos) were fed a control diet, diets containing 1, 5, 10, or 25 ppm Se as sodium selenite, or a diet containing 10 ppm Se as seleno-DL-methionine in the first of two experiments. Selenium at 10 ppm as selenomethionine or 25 ppm as sodium selenite caused a 40-44% decrease in the total number of eggs that hatched compared to controls. Selenium at 25 ppm (sodium selenite) resulted in a 19% decrease in mean embryonic weight at 18 d of incubation, accompanied by a 6% decrease in crown-rump length. Ten parts per million Se as selenomethionine was more teratogenic than sodium selenite at 25 ppm. Selenomethionine (10 ppm Se) resulted in an incidence of 13.1% malformations that were often multiple, whereas sodium selenite (10 and 25 ppm Se) resulted in 3.6 and 4.2% malformations. The teratogenicity of selenomethionine was confirmed in a second experiment in which mallards received 1, 2, 4, 8, or 16 ppm Se as selenomethionine, resulting in 0.9, 0.5, 1.4, 6.8, and 67.9% malformations, respectively. These malformations included hydrocephaly, microphthalmia, lower bill defects, and foot defects with ectrodactyly. Both forms of selenium increased the incidence of edema and stunted embryonic growth. Selenomethionine (10 ppm Se) resulted in a significant increase of approximately 40% in plasma glutathione peroxidase activity and a 70% increase in sorbitol dehydrogenase activity (indicative of hepatotoxicity) in hatchlings. Sodium selenite (25 ppm Se) resulted in fourfold elevation in plasma uric acid concentration, indicative of renal alteration. Selenomethionine accumulated much better in eggs than did sodium selenite. These findings indicate that selenomethionine is considerably more teratogenic and generally more embryotoxic than sodium selenite, probably due to higher uptake of selenomethionine.     

Selenite biotransformation to volatile metabolites in an isolated hepatocyte model system

The biotransformation of selenite to dimethylselenide was studied in an oxygenated hepatocyte model system. The concentrations of selenite used were 20-100 microM. A lag period of one hour or more, during which no net formation of selenide could be detected characterized the system. The maximal rate of volatilization was recorded during the second hour and was 0.13 nmoles/10(6) cells/min with 50 microM selenite. The rate then declined and volatilization eventually ceased. Two-thirds of the added amount of Se was lost within 4 hr. Oxidation of glutathione (GSH) by cumene hydroperoxide delayed volatilization. An inhibitor of gluconeogenesis, p-tert-butylbenzoic acid (3 microM) prevented volatilization. There were indications that GSSG reductase dependent metabolism was the only major metabolic pathway in hepatocytes under the conditions studied. During the lag period Se accumulated in cells, but was subsequently partially released during volatilization. The accumulation of Se was paralleled by an increase in oxygen uptake. The above mentioned inhibitors of volatilization prolonged the phase of accumulation. With 50 microM selenite the rate of accumulation was 0.06 nmoles/10(6) cells/min and maximally 30-35% of the added dose was retained in the cells. The results are compatible with the assumption that Se mainly accumulated as Se-glutathione complexes. The possibility that such complexes autooxidized and entered futile redox cycles during the lag period is discussed.     

亚硒酸钠对糖尿病模型大鼠肾组织中核转录因子-κB活性的干预作用

目的:探讨亚硒酸钠对不同时期糖尿病模型大鼠肾组织中核转录因子(NF)-κB活性的影响。方法:将糖尿病造模成功的SD大鼠随机分为糖尿病2个月组(DM2组)、4个月组(DM4组),糖尿病补硒(Se)2个月组(DM+Se2组)、4个月组(DM+Se4组),同时设正常对照2个月组(CON2组)、4个月组(CON4组)。各组给予不同饲料喂养2或4个月后进行相应处理,计算尿蛋白排泄率(UAER),检测大鼠血肌酐(Scr)、血浆尿素氮(BUN)、尿肌酐(Ucr)含量及肾组织中NF-κB活性。结果:DM+Se2组UAER、NF-κB活性水平高于CON2组(P<0.01)、低于DM2组(P<0.01);DM+Se4组Ucr含量低于CON4组(P<0.01),Scr、BUN、UAER水平及NF-κB活性均高于CON4组(P<0.01);DM+Se4组Ucr含量高于DM4组(P<0.01),Scr、BUN水平及NF-κB活性均低于DM4组(P<0.01)。结论:亚硒酸钠可能通过降低NF-κB活性而发挥保护糖尿病大鼠肾功能的作用。     

Structural basis of the antagonism between inorganic mercury and selenium in mammals

Mercuric chloride toxicity in mammals can be overcome by co-administration of sodium selenite. We report a study of the mutual detoxification product in rabbit plasma, and of a Hg-Se-S-containing species synthesized by addition of equimolar mercuric chloride and sodium selenite to aqueous, buffered glutathione. Chromatographic purification of this Hg-Se-S species and subsequent structural analysis by Se and Hg extended X-ray absorption fine structure (EXAFS) spectroscopy revealed the presence of four-coordinate Se and Hg entities separated by 2.61 A. Hg and Se near-edge X-ray absorption spectroscopy of erythrocytes, plasma, and bile of rabbits that had been injected with solutions of sodium selenite and mercuric chloride showed that Hg and Se in plasma samples exhibited X-ray absorption spectra that were essentially identical to those of the synthetic Hg-Se-S species. Thus, the molecular detoxification product of sodium selenite and mercuric chloride in rabbits exhibits similarities to the synthetic Hg-Se-S species. The underlying molecular mechanism for the formation of the Hg-Se-S species is discussed.     

Formation and possible role of bis(methylmercuric) selenide in rats treated with methylmercury and selenite

The metabolic fate of methylmercury after administration of [²⁰³Hg]-methylmercuric chloride in combination with sodium selenite was investigated in rats. Whole body autoradiography and radioassay showed that administration of selenite decreased the mercury concentration in the liver and kidney, and increased that in the brain. The rapid changes of methylmercury concentration in the tissues after selenite injection were accompanied by increases in mercury extractable with benzene at neutral pH. The maximum levels of benzene-extractable mercury in the blood, kidney and liver were attained 30 min after selenite injection and were 30, 23 and 8 percent, respectively, of the total mercury. Thin-layer chromatography showed that the benzene-extractable mercury was a complex of methylmercury with selenium, bis(methylmercuric) selenide. These findings indicate that selenite alters the distribution of methylmercury in the tissues by formation of a diffusible complex with methylmercury, bis(methylmercuric) selenide.