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。     

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。     

富硒麦芽对阿霉素致小鼠心脏毒性的保护作用

目的:探讨含硒制剂诱导金属硫蛋白在对抗阿霉素心脏毒性中的作用,比较无机硒制剂亚硒酸钠与有机硒制剂富硒麦芽。方法:不同时间给小鼠喂予硒制剂后取血分离血清,按常规查GOT和CK活性,按DTNB法测GSH-Px活性;取心、肝、肾组织按Hg Chelex法测金属硫蛋白(MT)含量并做心脏病理学检查。结果:两种含硒制剂均能减轻阿霉素引起的体重下降、GOT与CK酶升高及心脏病理损害,其中富硒麦芽的效果略优于亚硒酸钠。两者还能增加GSH-Px酶活性,诱导心脏中MT合成增加,连续使用硒制剂的整体效果优于先或后使用该制剂。结论:除升高GSH-Px外,硒制剂诱导合成MT很可能是减轻阿霉素心脏毒性的保护机制之一。两种硒制剂比较使用富硒麦芽较亚硒酸钠更为安全,且不降低原已证实的亚硒酸钠对心肌的保护作用。     

取代苯甲醛/肉桂醛缩氨基硒脲的合成及抗癌活性

硒为生命活动所必需的微量元素,如果人体内血硒含量长期低于0.1ppm,就有可能引起肝坏死、心肌损害、癌症、克山病、关节炎等疾病。近20多年来,为了预防疾病,许多国家已注意开发富硒的食物及在饮水或食物中加入亚硒酸钠、硒酵母等以补充含硒量的不     

富硒麦芽对阿霉素致小鼠心脏毒性的保护作用

目的：探讨含硒制剂诱导金属硫蛋白在对抗阿霉素心脏毒性中的作用,比较无机硒制剂亚硒酸钠与有机硒制剂富硒麦芽。方法：不同时间给小鼠喂予硒制剂后取血分离血清,按常规查ＧＯＴ和ＣＫ活性,按ＤＴＮＢ法测ＧＳＨ－Ｐｘ活性;取心、肝、肾组织按Ｈｇ－Ｃｈｅｌｅｘ法测金属硫蛋白（）含量并做心脏病理学检查。结果：两种含硒制剂均能减轻阿霉素引起的体重下降,ＧＯＴ与ＣＫ酶升高及心脏病理损害,其中富硒麦芽的效果略优于亚硒酸     

富硒酵母兔体内药物动力学研究

用金膜电极微分阳极溶出伏安法测定了富硒酵母在兔体内的药物动力学参数:半衰期(t_(1/2))4.15h,吸收速率常数(h_a)0.444h~(-1),消除速率常数(k)0.167h~(-1),药物达峰时间(T_(max))3.744h,药时曲线下面积(AUC_(0→∝))623.75ng/ml·h。实验结果表明,富硒酵母较亚硒酸钠具有生物利用度大、维持时间长、峰浓度高的特点,是一优于亚硒酸钠的补硒剂。     

富硒猫棒束孢菌丝的培养方法

目的制备富硒猫棒束孢,通过固体培养,实现无机硒向有机硒的生物学转化。方法在猫棒束孢常规培养过程中,加入无机硒化合物,采用高效液相色谱-电感耦合等离子体-质谱(HPLC-ICP-MS)法检测培养好的富硒猫棒束孢和非富硒猫棒束孢菌丝粉中有机硒含量,确定其生物转化率。结果 840 g小米和42 g葡萄糖中加入亚硒酸钠140 mg,平均可培养出富硒猫棒束孢菌丝粉280 g,所培养富硒猫棒束孢中有机硒含量为48.78μg/g,无机硒的的生物转化率为21.39%。结论在猫棒束孢常规固体培养过程中加入无机硒化合物(亚硒酸钠),可以成功实现无机硒的有机化转化,本方法可用于猫棒束孢的富硒培养。     

有机硒富硒麦芽与无机硒亚硝酸钠的毒性比较

目前我国缺硒地区解决硒营养不足问题,是采用口服无机亚硒酸钠片或食用亚硒酸钠强化食盐。然而不少研究表明,有机硒的活性比无机硒高。能更有效地在体内同化,且毒性小。北京市食品工业研究所研制的富硒麦芽,其有机硒的含量达97％以上。与美国研制的硒酵母相比,富硒麦芽还含有一定量的维生素E(V_E)和维生素C(V_C)     

亚硒酸钠联合抗痨药治疗HBV感染的肺结核病人临床研究

目的 探讨亚硒酸钠联合抗痨药治疗HBV感染的肺结核病人的疗效及对肝功能的影响。方法 将病人随机分为联合抗痨组和单纯抗痨组，定期观察临床症状，体征，胸部影像学改变及痰菌含量变化，并检测肝功能指标。结果 联合抗痨组有效率为91．7％，单纯抗痨组为79．0％（P＜0．05）；联合组肝损害率为11．7％，单纯组为25．8％（P＜0．05）。结论 亚硒酸钠联合抗痨药治疗肺结核优于单纯抗痨药物治疗，且亚硒酸钠具有保肝作用。     

硒对顺铂肾毒性的防护作用

大鼠亚硒酸钠2mg·kg~1·d~1 ip,连续2d,d 2给药后4 h ip顺铂5 mg/kg,能明显降低由ip顺铂引起的尿量、尿NAG活性及血尿素氮和血浆肌酐的升高,使尿渗透浓度维持正常水平,并使顺铂引起的大鼠肾脏近曲小管上皮细胞变性坏死明显减轻。亚硒酸钠在减少顺铂肾毒性的同时并不影响其抗癌效应。     

亚硒酸钠在兔体内的药代动力学

给家兔单次iv或ig Na_2SeO_3 2.0mg/kg,iv血药-时曲线符合线性三室开放模型,药代动力学参数为t_(3/2)a 0.16±0.08d,t_(1/2)β9.93±2.52d,t_(1/2)π0.13±0.08 h,ig血药-时曲线符合二室开放模型,药代动力学参数t_(1/2)(Ka)2.69±0.56h,t_(1/2)a 0.96±0.45d,t_(1/2) β9.31±3.36 d。多次给硒时,每7d,14d igNa_2SeO_3 2.0mg/kg,每10d iv Na_2SeO_3 1.5mg/kg各组达到90％以上稳态血药水平的时间分别为35d,45d和30d。     

Metallothionein induction by sodium selenite at two different ambient temperatures in mice

The induction of metallothionein (MT) synthesis by sodium selenite was investigated in mice with regard to the hypothermic response known to be caused by sodium selenite. Mice received a subcutaneous injection of sodium selenite at two doses (20 and 45 mol/kg) under two ambient temperature (22 and 33° C) conditions. Hepatic MT concentration was significantly increased by an injection of sodium selenite compared to the control, whereas no significant effect of ambient temperature was observed. The distribution of radiolabeled selenium was examined in vivo and in vitro. When sodium selenite was injected into mice, radiolabeled selenium was mostly eluted in a fraction larger in molecular weight than MT and was not found in a fraction corresponding to MT. When sodium selenite was added to the hepatic supernatant of the mice that had been injected with zinc sulfate, zinc in zinc-thionein was not displaced by radiolabeled selenium.     

Induction of apoptosis and autophagy by sodium selenite in A549 human lung carcinoma cells through generation of reactive oxygen species

Selenium in the form of sodium selenite has been reported to exert anti-tumor effects in several cancer cell types by inducing autophagic cell death and apoptosis mediated by reactive oxygen species (ROS). However, the exact molecular pathways underlying these effects have not been fully established. The present study used A549 human lung carcinoma cells for further investigation of the anti-cancer mechanism of sodium selenite. We showed that sodium selenite modulated both the extrinsic and intrinsic apoptotic pathways, which were interconnected by Bid truncation. We used z-VAD-fmk, a pan-caspase inhibitor, to demonstrate that sodium selenite-induced apoptosis was dependent on the activation of caspases. Sodium selenite also increased autophagy, as indicated by an increase in microtubule-associated protein light chain-3 (LC3) puncta, accumulation of LC3II, and elevation of autophagic flux. Pretreatment with bafilomycin A1 enhanced sodium selenite-induced apoptosis, indicating that sodium selenite-induced autophagy functioned as a survival mechanism. Sodium selenite treatment also resulted in generation of ROS, which abrogated mitochondrial membrane potential (MMP) and regulated both apoptosis and autophagy. Phospho-nuclear factor erythroid 2-related factor 2 (p-Nrf2) showed a ROS-dependent translocation to the nucleus, which suggested that Nrf2 might increase cell survival by suppressing ROS accumulation and apoptosis mediated by oxidative stress. Sodium selenite treatment of A549 cells therefore appeared to trigger both apoptosis and cytoprotective autophagy, which were both mediated by ROS. The data suggest that regulation of ROS generation and autophagy can be a potential strategy for treating lung cancer that is resistant to pro-apoptotic therapeutics.     

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.     

障复明治疗大鼠硒性白内障的实验研究

目的研究障复明对硒性白内障的治疗作用。方法Wistar大鼠幼鼠注射亚硒酸钠复制白内障模型。实验分为模型组及障复明高、中、低治疗组,未注射亚硒酸钠的同龄幼鼠作为空白对照组。定期观察各组动物晶体混浊情况,实验结束时检测各组晶体超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。结果障复明3个剂量组大鼠晶体混浊度低于模型组,晶体SOD活力显著高于模型组(P<0.05),而MDA含量显著低于模型组(P<0.05)。结论障复明对硒性白内障有较好的治疗作用,其作用强度与障眼明片相当。     

Elemental selenium particles at nano-size (Nano-Se) are more toxic to Medaka (Oryzias latipes) as a consequence of hyper-accumulation of selenium: a comparison with sodium selenite

Recent studies have shown that elemental selenium particles at nano-size (Nano-Se) exhibited comparable bioavailability and less toxicity in mice and rats when compared to sodium selenite, selenomethinine and methylselenocysteine. However, little is known about the toxicity profile of Nano-Se in aquatic animals. In the present study, toxicities of Nano-Se and selenite in selenium-sufficient Medaka fish were compared. Selenium bioaccumulation and subsequent clearance in fish livers, gills, muscles and whole bodies were examined after 10 days of exposure to Nano-Se and selenite (100mug Se/L) and again after 7 days of depuration. Both forms of selenium exposure effectively increased selenium concentrations in the investigated tissues. Surprisingly, Nano-Se was found to be more hyper-accumulated in the liver compared to selenite with differences as high as sixfold. Selenium clearance of both Nano-Se and selenite occurred at similar ratios in whole bodies and muscles but was not rapidly cleared from livers and gills. Nano-Se exhibited strong toxicity for Medaka with an approximately fivefold difference in terms of LC(50) compared to selenite. Nano-Se also caused larger effects on oxidative stress, most likely due to more hyper-accumulation of selenium in liver. The present study suggests that toxicity of nanoparticles can largely vary between different species and concludes that the evaluation of nanotoxicology should be carried out on a case-by-case basis.     

Hemolytic Effects of Sodium Selenite and Mercuric Chloride in Human Blood

Many works have reported the interaction between selenium and mercury in the mammalian body and that chalcogen seems to have a protective effect against mercury toxicity. The aim of this study was to investigate the hemolytic effects of sodium selenite and/or mercuric chloride in human blood under in vitro conditions. For this, total venous blood from healthy subjects (males and females) was heparinized and incubated at 37°C for 90 min with different concentrations of sodium selenite and/or mercuric chloride. The hemolytic effects of compounds were evaluated by measuring plasma hemoglobin concentration after centrifugation. In addition, 2-thiobarbituric acid reactive substances (TBARS) from plasma and erythrocytes, as well as erythrocyte nonprotein thiols (NPSH), were also evaluated in order to investigate molecular mechanisms related to selenite- or mercury-induced hemolysis. Mercuric chloride and sodium selenite, alone (400 µM), promoted a small in vitro hemolytic effect in human erythrocytes. However, when blood was exposed to both compounds (200 µM of each), there was an extremely high synergistic hemolytic effect. The exposure of blood to sodium selenite (400 µM), mercuric chloride (400 µM), and both compounds (200 µM each) did not alter erythrocyte TBARS levels. Sodium selenite presented a high oxidant effect toward erythrocyte NPSH; however, this effect was inhibited by mercuric chloride. The current results point to a synergistic hemolytic effect of sodium selenite and mercuric chloride in human blood, suggesting new understanding on the selenium–mercury antagonism. Moreover, this observed hemolysis seems to be not related to lipoperoxidation or thiol depletion.     

Subacute oral toxicity investigation of selenium nanoparticles and selenite in rats

Selenium (Se) nanoparticles have been proposed as food supplements. However, the particle formulation may exert unexpected toxicity. The aim was therefore to compare toxicity of low doses of Se nanoparticles and the dissolved, ionized Se species selenite. Female rats were dosed orally for 28?d with either: 0.05, 0.5, or 4?mg Se/kg body weight (bw)/day as 20?nm Se nanoparticles or 0.05 or 0.5?mg Se/kg bw/day as sodium selenite. Male rats were dosed 4?mg Se/kg bw/day as Se nanoparticles. Body weight and clinical appearance were recorded throughout the experiment. At necropsy, blood samples were taken for hematological and clinical chemistry analyses; organ weights were recorded. At the high-dose of Se nanoparticles, overt toxicity occurred and the female animals had to be euthanized prematurely, whereas the male animals were reduced in dose. At all doses of Se nanoparticles and at 0.5?mg Se/kg bw/day as selenite, a lower body weight gain as compared to vehicle occurred. Relative liver weight was increased for both Se formulations at 0.5?mg Se/kg bw/day. Creatinine clearance and urinary pH were affected in some Se dosed groups. There were no effects among dosed groups on brain neurotransmitters or on hematological parameters compared with controls. There were no histological changes in the livers of animals exposed to Se nanoparticles or to selenite. Based on effects on body weight and liver weight, selenium nanoparticles and ionic Se exerted similar toxicity. This suggests that a nanoparticle-specific toxicity of Se did not occur.