微量元素对铅毒性的影响

膳食中微量元素锌,铁和硒可影响人体对铅毒性的敏感性。铁缺乏可使铅吸收和毒性增强,铅可影响血红素合成途径中铁的代谢。由于缺铁本身可影响儿童智力发育,因此铅暴露和铁缺乏与儿童认知和赤发育损伤可能有一定关系。硒可轻度拮抗铅毒性。锌的营养状况可影响组织中铅蓄积和机体对铅毒性的敏感性,铅 对称站缺乏可能导致血红素合成和药物代谢受阻,影响血中含锌酶的活性;锌在一定程度上还可拮抗铅对细胞的毒性作用。     

十种化合物对大鼠游离肝细胞联合毒性的研究

采用细胞毒理学方法，以大鼠游离肝细胞半数中毒浓度（ＴＣ５０）为观察指标，对镉、硒、铜、砷、锑、汞、锌、铅、铬、镍１０种金属及类金属组成２９个配对进行了联合毒性的研究。结果表明，１０种金属及类金属化合物肝细胞毒性大小顺序是汞＞镉＞铅＞砷＞锑＞铜＞铬＞镍＞锌＞硒，与体内肝毒性顺序基本一致。汞、镉、铅三种金属之间有增毒作用，对其它金属的毒性亦有增强作用。锌可以拮抗镉、铅的毒性作用，硒可以保护汞、砷对细胞的毒性，其余金属配对呈毒性相加作用。铬和砷对镉的细胞毒性表现为拮抗作用，其机理需要进一步进行研究。     

29对金属化合物对大鼠游离肝细胞联合毒性的研究

本文以大鼠游离肝细胞半数中毒浓度（ＴＣ５０）对镉，硒，砷，锑，汞，锌，铅，铬，镍１０种金属组成２９个配对进行了联合毒性的研究，结果表明：１０种金属化合物肝细胞毒性大小顺序是汞＞镉＞铅＞砷＞锑＞铜＞铬＞镍＞锌＞硒，与体内肝毒性顺序基本一致，汞，镉，铅三种金属之间的增毒作用，对其它金属的毒性亦有增毒作用。锌可以拮抗镉，铅，铜的毒性作用，硒可以拮抗汞，镉，砷对细胞的毒性，其余金属配对呈毒性相加作用，铬和     

硒对铅毒性的拮抗作用

近年来,随着对硒研究的不断深入,人们发现硒有拮抗铅毒性的作用:一方面硒是体内抗氧化系统的重要组成成分,能明显改善铅中毒诱发的脂质过氧化反应,减轻铅的危害;另一方面硒与金属有很强的亲和力,可在体内与铅结合形成金属硒蛋白复合物,从而可降低铅的毒性作用。本文从硒拮抗铅毒性作用的机理、硒对铅毒性的拮抗作用以及不同形式的硒对铅毒性作用的影响三个方面综述了硒与铅毒性之间的关系。     

铅锌联合作用对仔鼠学习记忆行为的影响

目的探索能拮抗铅毒性的锌剂量，为防制铅毒害提供理论依据。方法从妊娠期开始建立空白组、染铅组、不同剂量锌与铅联合作用的仔鼠模型，在仔鼠出生后21d测定鼠血锌、脑锌及血铅、脑铅，并用暗箱电击法进行行为学测试。结果锌可以降低血铅浓度，但却不能使脑铅浓度降低。铅可降低仔鼠的学习记忆能力，中等剂量及高剂量的锌能拮抗铅的作用，且此2组仔鼠学习记忆能力与空白对照组相比差异无显著性。结论中等剂量的锌可以拮抗铅的毒性。     

利用大鼠游离肝细胞的生化指标研究金属化合物的联合毒性

采用大鼠游离肝细胞，以细胞培养基上清液山梨醇脱氢酶（ＳＤＨ）、谷丙转氨酶（ＧＰＴ）活性和肝细胞还原型谷胱甘肽（ＧＳＨ）作为观察指标，对镉、硒、铜．砷、锑、汞、锌、铅、铬、镍１０种金属化合物组成２９个配对进行了联合毒性研究。结果表明，汞、镉、铅３种金属之间有增毒作用．且它们增加其它金属的毒性，而锌可以拮抗镉、铅、铜的毒性作用．硒可以保护汞、镉、砷对细胞的毒性，其余配对呈毒性相加。     

金属元素对人胚肺细胞联合毒性的研究

采用细胞毒理学方法，以人胚肺细胞半数中毒浓度（ＴＣ５０）为观察指标，对铅、汞、砷、镉、镍、锰、锌、硒等８种金属元素组成２７个配对进行联合毒性的研究。结果表明，８种金属元素肺细胞毒性大小顺序是汞＞镉＞锰＞镍＞砷＞铅＞锌＞硒，与体内肺毒性顺序基本相似。铅、镉、汞、锰３种金属元素之间有增毒作用。锌和硒对铅、镉、汞、砷的细胞毒性有拮抗作用。     

56例铅作业工人血锌原卟啉检测分析

５６例铅作业工人血锌原卟啉检测分析广州市职业病防治院肖妙容，麦兆生红细胞内锌原卟啉（ＺＰＰ）是机体受铅毒作用后的异常代谢产物。ＺＰＰ的浓度可反映铅对造血系统代谢的影响，有资料认为ＺＰＰ的敏感度超过尿铅，且操作简便、快速，是一个可靠、敏感的铅中毒早期诊...     

我国儿童铅中毒的研究现状

铅（Pb）是一种具有神经毒性的重金属元素，在人体内无任何生理功能，其理想的血浓度为零。但由于环境中铅的普遍存在，绝大多数人体中均或多或少存在，当铅在体内的存在量超过一定水平时就会对人体的健康产生危害，造成神经、生殖等系统的疾患。儿童、少年由于新陈代谢和生长发育的特点，对铅毒性特别敏感。据调查，我国儿童血铅浓度超标率大于50％，部分工业城市更高达80％。这种情况已引起国内外儿少卫生工作者的广泛重视，进行了大量的调查研究，现将研究结果综述如下。     

儿童高铅血症及轻度铅中毒的药物干预

铅在人体内是一种具有多系统毒性的重金属元素,铅对儿童的损害更敏感。对于高铅血症及轻度铅中毒的防治尚缺乏公认显著有效的药物,但铅中毒对儿童的智力和身体发育都存在不利影响。近年来,临床使用一些维生素、金属硫蛋白、微量元素和中药等对儿童轻度铅中毒进行治疗,这些药物在减少铅在胃肠道的吸收、降低血铅水平、改善铅中毒症状方面发挥作用。     

Maintenance of zinc-dependent hepatic functions in rat hepatocytes cultured in medium without added zinc

Hepatocytes were cultured with Waymouth's media containing zinc at concentrations of 1 (the endogenous zinc concentration of basal medium), 16 and 48 mumols Zn/L to examine the effects of extracellular zinc on a variety of zinc-related functions. The zinc concentrations were chosen with the intention of simulating zinc-deficient, adequate and excess extracellular conditions. Basal medium had no effect on cell zinc, metallothionein (MT) or MTmRNA for up to 48 h but reduced delta-aminolevulinic acid dehydratase (delta-ALA-D) activity to 75% of the initial level by 3 h. The addition of zinc at 16 or 48 mumols Zn/L during the initial 3 h of culture did not prevent the decrease in delta-ALA-D activity. Reintroducing zinc at concentrations of 16 or 48 mumols Zn/L to hepatocytes after the initial 3 h of culture in basal medium significantly increased cell zinc, MT and MTmRNA levels and fully restored delta-ALA-D activity by 24 h. Medium zinc had no apparent effect on membrane integrity assessed as leakage of lactate dehydrogenase activity into culture media or de novo protein synthesis as examined by two-dimensional gel electrophoresis of 35S-labeled proteins. Hepatocytes cultured in basal medium resisted losses in cell zinc concentration even when EDTA and bovine serum albumin were present in culture medium. Kinetic experiments using 65Zn suggest hepatocytes maintain zinc concentrations by reducing zinc efflux. The ability of hepatocytes cultured in basal (1 mumol Zn/L) medium to maintain cell zinc content and some zinc-dependent functions underscores the difficulty of producing zinc deficiency in primary hepatocyte culture.     

福建水华微囊藻粗毒素对原代培养大鼠肝细胞毒性作用的初步研究

[目的]用直接分离法进行大鼠肝细胞体外培养．研究微囊藻毒素的毒性。[方法]以大鼠作为肝细胞供体,用直接分离法制备肝细胞,进行原代培养后加入不同浓度的藻毒素;在培养的不同时期用台盼蓝排斥法计算贴壁的活细胞数及存活率,用倒置显微镜观察肝细胞形态变化。[结果]①不同浓度的藻毒索对大鼠肝细胞具有毒性作用,呈现出剂量一反应关系。②直接分离法可得到大量单个分散的肝细胞,细胞数量能够满足毒理学的实验要求,在41h内细胞生长较好,适于进行细胞毒理学的实验;65h后肝细胞功能和活力欠佳,不适于实验。[结论]微囊藻毒素对体外培养的肝细胞有毒性作用;直接分离法获取肝细胞进行原代培养的方法可用于短期细胞毒理学的实验研究。     

Metallothionein concentrations in natural populations of gudgeon (Gobio gobio): relationship with metal concentrations in tissues and environment

A field monitoring campaign investigating the suitability of (Cd, Zn)-metallothionein concentrations (MTs) in different tissues of the gudgeon as a biomarker for metal contamination in the aquatic environment was conducted. Gudgeons were captured at 10 sampling sites on a river system in Flanders (Belgium). Nine sampling sites were situated along a Cd and Zn gradient with a nearby tributary as the reference site. Cadmium, Cu, and Zn concentrations were measured in the water and sediments. Concentrations of (Cd, Zn)-MT were measured in different organs (gill, liver, kidney) of gudgeon (Gobio gobio). The hepatic and gill Cd and Zn concentrations, as well as the hepatic (Cd, Zn)-MT concentrations, reflected the polymetallic contamination gradient. Moreover, the hepatic Cd and Zn concentrations could describe 72% of the variance in the (Cd, Zn)-MT concentrations in the liver, illustrating the possible use of hepatic MT concentrations as a biomarker for environmental metal contamination. In this way a dose-response relationship could be established under natural conditions. However, a poor negative relation between the Cd and Zn concentrations in the gills and the corresponding (Cd, Zn)-MT concentrations was found. No relation between the Cd and Zn concentrations in the kidney tissue and the corresponding (Cd, Zn)-MT concentrations could be established. These results clearly illustrate the tissue-specificity of the MT concentrations, thus for monitoring purposes MT concentrations should be measured in liver tissues, rather than in kidney or gill tissues.     

Exposure of human proximal tubule cells to cd2+, zn2+, and Cu2+ induces metallothionein protein accumulation but not metallothionein isoform 2 mRNA.

The organization of the human metallothionein (MT) gene family is more complex than the commonly used mouse and rat models. The human MTs are encoded by a family of genes consisting of 10 functional and 7 nonfunctional MT isoforms. One objective of this study was to determine if the accumulation of MT protein in cultures of human proximal tubule (HPT) cells exposed to metals is similar to that expected from the knowledge base obtained from rodent models. To accomplish this objective, HPT cells were exposed to both lethal and sublethal concentrations of Cd2+, Zn2+, Cu2+, Ag2+, Hg2+, and Pb2+ and MT protein levels were determined. The results were in general agreement with animal model studies, although there were some exceptions, mainly in areas where the animal model database was limited. In clear agreement with animal models, Cd2+, Zn2+, and Cu2+ were demonstrated to be potent inducers of MT protein accumulation. In contrast to the similarity in MT protein expression, we obtained evidence that the human renal MT-2 gene has a unique pattern of regulation compared to both animal models and human-derived cell cultures. In the present study, we determined that MT-2A mRNA was not induced by exposure of HPT cells to Cd2+ or the other metals, a finding in contrast to studies in both animal models and other human cell culture systems in which a high level of MT-2 mRNA induction occurs upon exposure to Cd2+ or Zn2+. While MT protein expression may be similar between humans and animal models, this finding provides initial evidence that regulation of the genes underlying MT protein expression may be divergent between species.     

Dietary zinc deficiency and repletion modulate metallothionein immunolocalization and concentration in small intestine and liver of rats

Metallothionein (MT) functions in zinc (Zn) homeostasis and dietary Zn affects tissue MT concentration. The objective of this study was to investigate the effects of dietary Zn deficiency and 24-h Zn repletion on MT immunolocalization and concentration in the small intestine and liver of growing rats. Three-week-old rats fed Zn-deficient diet (< 1 mg Zn/kg) for 16 d had no MT staining in either small intestine or liver. After 24-h Zn repletion with control diet (30 mg Zn/kg), strong MT staining was observed in intestinal Paneth cells and surface epithelial cells in the proliferative regions of villi. Pair-fed control rats had strong MT staining in liver that was localized around central veins. After 24-h energy repletion, the hepatic MT staining diminished. Furthermore, Zn-deficient rats had significantly reduced intestinal (57%) and hepatic (61%) MT concentrations but unaffected Zn concentrations compared with controls that consumed food ad libitum. Zn repletion for 24 h restored intestinal and hepatic MT concentrations and reduced hepatic Zn concentration. Pair-fed control rats had elevated MT concentration in liver that was normalized by energy repletion. There was a significant positive correlation between tissue Zn and MT concentrations in liver (r = 0.60, P = 0.0001), but not in small intestine. In summary, MT immunolocalization and concentration in rat small intestine and liver were responsive to changes in Zn status, supporting the role of MT in Zn metabolism. Cell-type-specific localization of MT in small intestine after dietary Zn manipulations indicates a function of Zn and MT in gut immunity and intestinal mucosal turnover, and the pattern of hepatic MT distribution with energy restriction may be linked to detoxification processes.     

Induction and metal speciation of metallothionein in wood mice (Apodemus sylvaticus) along a metal pollution gradient

We investigated the binding of Cd, Cu, and Zn to metallothionein (MT) and other metal-binding proteins in free-living wood mice (Apodemus sylvaticus L.) captured in four areas along a metal pollution gradient. We measured total and cytosolic Cd, Cu, and Zn concentrations in mouse liver and kidney by means of inductively coupled plasma-mass spectrometry (ICP-MS). Total (Cu, Cd, Zn)-MT levels were determined in the same tissues by means of the cadmium thiomolybdate saturation assay. Metal speciation of metalloproteins was studied by means of size-exclusion high-performance liquid chromatography-ICP-MS. Liver and kidney of wood mice from the site adjacent to the pollution source showed the highest Cd and Zn concentrations (total and cytosolic) and (Cu, Cd, Zn)-MT levels compared to the other sites farther away from the pollution source. No or only small site differences in tissue Cu concentrations were observed. Almost all the variation (85-95%) in hepatic and renal (Cu, Cd, Zn)-MT levels was explained by the total or cytosolic hepatic Zn and Cd concentration or the renal Cd concentration, respectively. An analysis of the cytosolic metal speciation showed that the Cd-MT, Cu-MT, and Zn-MT fractions in liver and kidney increased significantly with increasing cytosolic metal concentrations. Metals associated with the other cytosolic protein fractions did not increase with increasing exposure. These results illustrate the important role of MT in metal homeostasis and detoxification processes. We conclude that MT is a useful biomarker for environmental metal contamination in free-living wood mice.     

Iron-induced metallothionein in chick liver: a rapid, route-dependent effect independent of zinc status

The induction of hepatic metallothionein (MT) by the parenteral administration of iron was studied. Iron administered to chicks by intravenous or subcutaneous injection caused a 1.9-fold increase in hepatic MT. In marked contrast, intraperitoneal (ip) Fe resulted in a 10-fold increase, thus demonstrating the importance of the route of metal administration. This route-dependent effect was found to be dose-dependent, with ip injections between 1 and 10 mg Fe/kg resulting in a linear increase in MT and a concomitant reduction in serum zinc concentration and feed intake. High ip doses of Fe resulted in a persistent depression in serum Zn and elevated MT and MTmRNA. Equimolar ip injections of either Zn or Fe showed similar patterns of MTmRNA accumulation. In both cases MTmRNA levels were elevated by 3 h, with a peak at 6 h postinjection (Fe 8-fold, Zn 12-fold above 0 h). Plasma Zn was maximally reduced by Fe at 9 h (60%). The MT induction by Fe, as well as related depression in plasma Zn, was completely inhibited by actinomycin D. Zn depletion eliminated the accumulation of hepatic Zn and MT protein following ip injection of Fe or endotoxin, but not of cadmium, despite marked elevation of hepatic MTmRNA. Our results demonstrate Fe injected into the body cavity of chicks results in a rapid induction of hepatic MT that, like endotoxin induction, is independent of dietary Zn status.     

Effect of cadmium on hepatic metallothionein level in early development of the rat

The induction of hepatic metallothionein (MT) was investigated 24 hr after an intraperitoneal injection of 0.75 mg/kg Cd as CdCl₂ · H₂O in rats of 7, 14, 21, and 90 days. Metallothionein in liver cytosolic fractions collected on Sephadex G-75 was characterized in terms of sulfhydryl, total protein, Cd, and Zn contents. Most of the cytosolic Cd was associated with MT and the concentration of Cd was equal in the different age groups. The higher contents of sulfhydryl, protein, and Zn both in control as well as in Cd-injected rats of 7 and 14 days than in those of 21 and 90 days indicate the presence of more native Zn-thionein in immature pups. However, the increase in sulfhydryl and protein contents showed more prominent induction of MT in Cd-exposed animals of 21 and 90 days than in those of 7 and 14 days. The concentration of Cd was highest in liver followed by the other tissues. While hepatic accumulation of Cd was similar in all age groups, the renal accumulation increased significantly with age. The intestine and spleen of immature pups concentrated more Cd than those of mature animals. The accumulation of the metal did not differ significantly in heart and brain of the animals among the four groups.     

Assimilation and bioconcentration of Ag and Cd by the marine black bream after waterborne and dietary metal exposure

We determined the aqueous uptake and dietary assimilation of Cd and Ag by the marine black bream Acanthopagrus schlegeli following one to four weeks' exposure (or conditioning) to waterborne or dietary Cd or Ag at different concentrations. The concentrations of metals and metallothioneins (MT) in different tissues also were determined. The viscera contained the highest Ag, Cd, and MT concentrations after metal exposure. After exposure to waterborne metals, the metal and MT concentrations in the gills were higher than those in the remaining tissues (mainly muscles and bones), but this pattern was reversed following exposure to dietary metals. The assimilation efficiencies (AEs) of Cd and Ag ranged from 6 to 24% and 15 to 30%, respectively. The rate constant of uptake from the dissolved phase (ku) of Cd and Ag ranged from 2.2 to 7.5 and 8.0 to 31.7 L kg(-1) d(-l), respectively. In all the exposure experiments, the ku and AE increased with induced MT concentration and tissue metal concentration. Increasing metal accumulation may have been due to the increased available binding sites following the induction of MT in the fish. Furthermore, the MT induced by either Cd or Ag was not specific, but was able to bind with both metals and enhance bioaccumulation. Exposure to dissolved and dietary metals may increase metal accumulation, which potentially may lead to metal toxicity, although the fish may develop a tolerance to metals due to the apparent induction of MT.     

乙醇对铁过载大鼠肝细胞脂质过氧化和胶原代谢的影响

目的：研究乙醇对铁过载大鼠肝原代细胞脂质过氧化反应和胶原合成的影响。探讨铁和乙醇在诱导肝细胞脂质过氧化反应时的相互关系，以及脂质过氧化反应对胶原合成的影响。方法：在饲料中添加３％（ｗ／ｗ）的Ｃａｒｂｏｎｙｌｉｒｏｎ造成铁过载动物模型，从铁过载大鼠和正常大鼠中分离来的肝原代细胞与不同浓度的乙醇（０、２５、５０、１００ｍｍｏｌ／Ｌ）及０．５ｍｍｏｌ／Ｌ去铁敏（ｄｅｓｆｅｒｏｘａｍｉｎｅ）共同培养２４小时。测定肝组织和细胞中铁含量，肝细胞成活率，肝细胞中脂质过氧化产物丙二醛（ＭＤＡ），还原型谷胱甘肽（ＧＳＨ）、羟脯氨酸含量。结果：铁过载组肝细胞铁含量明显高于对照组，而从铁过载组分离来的肝细胞随乙醇剂量的增加细胞中ＭＤＡ、羟脯氨酸含量增加、ＧＳＨ含量下降，加入０．５ｍｍｏｌ／Ｌ去铁敏可有效地抑制此变化。结论：铁和乙醇在诱导肝细胞脂质过氧化反应时存在协同作用，肝细胞内铁含量增高可增加乙醇的肝细胞毒性，铁和乙醇诱导的脂质过氧化反应／产物可刺激肝细胞胶原的合成