Mechanisms of selenium methylation and toxicity in mice treated with selenocystine

 Mechanisms of selenium methylation and toxicity were investigated in the liver of ICR male mice treated with selenocystine. To elucidate the selenium methylation mechanism, animals received a single oral administration of selenocystine (Se-Cys; 5, 10, 20, 30, 40, or 50 mg/kg). In the liver, both accumulation of total selenium and production of trimethylselenonium (TMSe) as the end-product of methylation were increased by the dose of Se-Cys. A negative correlation was found between production of TMSe and level of S-adenosylmethionine (SAM) as methyl donor. The relationship between Se-Cys toxicity and selenium methylation was determined by giving mice repeated oral administration of Se-Cys (10 or 20 mg/kg) for 10 days. The animals exposed only to the high dose showed a significant rise of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in plasma. Urinary total selenium increased with Se-Cys dose. TMSe content in urine represented 85% of total selenium at the low dose and 25% at the high dose. The potential of Se-methylation and activity of methionine adenosyltransferase, the enzyme responsible for SAM synthesis, and the level of SAM in the liver were determined. The high dose resulted in inactivation of Se-methylation and decrease in SAM level due to the inhibition of methionine adenosyltransferase activity. To learn whether hepatic toxicity is induced by depressing selenium methylation ability, mice were injected intraperitoneally with periodate-oxidized adenosine (100 μmol/kg), a known potent inhibitor of the SAM-dependent methyltransferase, at 30 min before oral treatment of Se-Cys (10, 20, or 50 mg/kg). Liver toxicity induced by selenocystine was enhanced by inhibition of selenium methylation. These results suggest that TMSe was produced by SAM-dependent methyltransferases, which are identical with those involved in the methylation of inorganic selenium compounds such as selenite, in the liver of mice orally administered Se-Cys. Depression of selenium methylation ability resulting from inactivation of methionine adenosyltransferase and Se-methylation via enzymic reaction was also found in mice following repeated oral administration of a toxic dose of Se-Cys. The excess selenides accumulating during the depression of selenium methylation ability may be involved in the liver toxicity caused by Se-Cys. Received: 27 March 1996/Accepted: 19 June 1996     

亚硝酸钠对饲克山病病区粮大鼠花生四烯酸代谢影响

以低硒（Ｓｅ）低维生素Ｅ（ＶＥ）的克山病病区粮饲养大鼠１０周，用腹腔注射亚硝酸盐引起急性缺氧的方法，观察花生四烯酸代谢及其主要产物水平的变化。结果表明，病区粮组大鼠磷脂酶Ａ２活力、花生四烯酸含量、血栓素水平、血栓素／前列环素比值增高；前列环素水平、抗氧化酶活力降低；补Ｓｅ和ＶＥ可使上述变化逆转。结果提示，花生四烯酸代谢紊乱、抗氧化能力降低，是亚硝酸钠与Ｓｅ和ＶＥ缺乏协同引起心肌损害的作用环节。     

硒对提高胃肠癌患者术前免疫水平的探讨

本将３１例胃肠癌患分为治疗组和对照组（未加服硒），观察术前投药前后血清硒浓度与Ｔ淋巴细胞亚群、ＮＫ细胞的活性的变化。结果显示：胃肠癌患入院时血硒水平为０．８２５±０．１１μｍｏｌ／Ｌ，低于正常对照组，口服硒剂后血硒浓度升高，与对照组相比差异有显性，服硒后血中ＣＤ３、ＣＤ４、ＣＤ８细胞以及ＣＤ４／ＣＤ８细胞比值仍维持原有的水平，但对照组有所下降（Ｐ〈０．０５）〉值得注意的是服硒后患血中ＮＫ     

富硒粮中的硒对大鼠体内铅及硒含量的影响

本文选用２０只ＷＫＨ系大鼠，随机分成两组，采用腹腔注射给铅法，同时饲以富硒粮和常硒。断脊处死取样，消化后测大鼠组织的铅和硒含量。结果表明，饲以富硒粮组的大鼠体内各组织的铅含量均低于饲以常硒粮组，硒含量均高于常硒粮组。     

补硒对冠心病患者生活质量影响的临床观察

目的　观察补硒对冠心病患者生活质量的影响。方法　冠心病患者 1 89例 ,对照组内科药物治疗。补硒组加服有机硒 ,每三个月进行一次随访评估 ,随访时间为一年。结果　补硒组生活质量综合评分由治疗前的 53 .62± 8.30提高至治疗后的 58.0 1± 8.93 ,治疗前后差异性显著 (P <0 .0 0 1 ) ;与对照组治疗前后比较差异显著 (P <0 .0 0 1 )。结论　对比观察证明 ,补硒能提高冠心病者的生活质量。     

氟硒对大鼠甲状腺组织及功能的影响

观察了饮用高氟水及加硒大鼠的甲状腺组织结构和甲状腺激素变化。结果表明，早期甲状腺滤泡上皮细胞增生活跃、游离甲状腺激素水平显著升高；后期甲状腺滤泡上皮细胞出现退行性变，ＦＴ３和Ｔ４水平明显降低；补硒与甲状腺激素水平有一定关系。提示高氟在早期使甲状腺兴奋，甲功高度代偿，后期则抑制甲状腺使甲功低下；氟与甲状腺组织及功能的改变与摄氟时间密切相关。     

硒镉联合作用的细胞遗传学效应

本研究通过对小鼠腹腔注射硒、镉化合物,以观察其对小鼠的单独和联合的遗传学效应。结果表明:氯化镉和亚硒酸钠均能单独引起姐妹染色单体交换(SCE)频率和精子畸形率明显升高,细胞增殖指数(PRI)明显下降。当硒、镉联合作用时,亚硒酸钠可明显对抗氯化镉的遗传毒性。     

克山病人体组织中硒水平研究

本文对云南克山病及其他疾病死亡者的心、肝、肾和胸肌四种具有代表性的组织进行了硒含量测定分析,表明克山病人四种组织中硒含量均低于国内和国外健康人相应组织;亚急克四种组织中硒含量均相应地较慢克低;心肌硒含量又比其肾、肝组织为低,均有显著性差异。进一步证实了克山病人体内环境确实处于低硒状态。     

硒和汞在汞污染区放养家鸭脏器中的分布

通过对松花江肇源江段放养的家鸭脏器中硒和汞的实验研究 ,发现观察组鸭内脏总汞含量由高到低的顺序为肝 >肌肉 >脑 >心 >肾 >肺 ,对照组为肺 >肾 >肝 >心 >脑 ,两组鸭脏器中汞含量除肺外均有显著性差异 ,观察组显著高于对照组 ;观察组硒含量由高到低的排列顺序为心 >肺 >睾丸 >脑 >肌肉 >肝 ,对照组为脑 >肺 >血液 >心 >肝 >肌肉 ,两者的排列顺序不同 ,而且两组鸭脏器硒含量有显著性差异。对鸭肝硒和汞含量做相关性分析 ,相关系数r=- 0 932 ,P <0 0 0 1,呈显著负相关。     

硒对颗粒活性炭净化水毒性的防护作用

本文对颗粒活性炭净化饮水的亚慢性毒性、遗传毒性和对细胞免疫功能的影响及硒对以上毒性作用的防护作用进行了试验研究。研究选用昆明和BALB/C两种小鼠。实验周期100天。结果显示,颗粒活性炭净化水有一定的亚慢性毒作用,其表现为动物血清白蛋白下降,血肌酐升高和肝、肾组织出现有意义的病理变化。硒(0.5mg/L)能够减轻上述毒性反应。作用机制可能与硒有效提高动物全血GSH-PX活性和增强细胞免疫功能有关。