Native and induced rat kidney metallothioneins and their relation to cadmium toxicity

The concentrations of zinc, copper, iron, manganese, magnesium, and phosphorus in the kidneys were determined for control female rats of five different ages (4, 8, 12, 16, and 20 weeks old). The concentration of copper increased with age and it was attributed to three metallothionein peaks on a SW 3000 column. Parenteral administration of Cd-thionein caused swelling of kidneys to different degrees, depending on the age of the rats; the youngest rats were affected most. The concentrations of cadmium and the six metals in the kidneys at 12 hr and 7 days after injection were determined and compared with controls. The distribution among protein fractions of cadmium, zinc, and copper, which are related to metallothionein, were examined by gel permeation chromatography. The elution profiles of the three metals changed not only with the ages of the rats but also with time after injection. The changes were correlated with the copper content in the metallothioneins and with swelling of the kidneys. The changes also correlated with native metallothionein levels.     

外源性的锌诱导兔肝金属硫蛋白对原代肝细胞铅毒性的保护作用

锌诱导兔肝金属硫蛋白（Zn7-MT)是一种富含半胱氨酸的低分子量的锌结合蛋白，在金属代谢和解毒方面起着十分重要的作用。本项研究是采用外源性的MT在鼠原代肝细胞（RPHC）中，对金属铅毒性方面所起的保护作用进行研究，其方法是将RPHC单层培养24小时，然后加入一定浓度的（Zn7-MT)后，并将RPHC在各种浓度铅中，实施暴露24小时，分别测定细胞乳酸脱氢酶的渗出量和K^ 的损失来评价它们对细胞的毒性作用，同时，研究铅在细胞内，外的铅元素的分布和吸收情况，以及在Zn7-MT的存在下，探讨Zn7-MT在RPHC中对铅毒性方面所起的作用，实验结果证明，在Zn7-MT的存在下，铅对细胞的毒性作用显著性降低，其细胞对铅元素的吸收和聚集产生一定的改变，在对照组细胞的胞质中，铅可能主要与高分子量的蛋白结合，而在Zn7-MT存在下，这些金属可能主要与Zn7-MT相结合。     

锌对原代培养海马神经元MT mRNA表达的影响

目的　为探讨神经元锌内稳态机制。方法　采用实时荧光定量RT PCR法检测 :原代培养大鼠海马神经元 10 0 μmol L锌诱导后 ,不同时间点 (0、2、4、6和 8h)MT1 MT2 MT3mRNA的表达 ;及 0、5 0、75、10 0、12 5、15 0 μmol L锌诱导 4h后 ,各浓度组MT1 MT2 MT3mRNA的表达。 结果　基础状态下 ,MT的三个异构体在海马神经元内的表达峰度为 :MT3>MT1>MT2 ;在 0～ 10 0 μmol L范围内 ,MT1、MT2mRNA的表达随锌浓度增加而显著增加 ,锌浓度进一步增加时 ,MT1、MT2mRNA的表达进入平台期 ;MT3mRNA的表达随锌浓度的升高而下降 ;锌可显著上调MT1和MT2mRNA表达 ,峰值时间点在 6h左右 ;锌可使MT3mRNA的含量降低约6 0 %。结论　除MT3mRNA外 ,MT1和MT2mRNA在神经元内也有表达 ;象神经胶质细胞一样 ,神经元同样可通过增加MT1和MT2mRNA的表达以维持锌内稳态     

锌,硒单独与联合作用对镉毒性拮抗作用的研究

本研究对镉，锌，硒单独或同时给与时相互之间的作用及影响进行了测定，以观察锌，硒对镉毒性的拮抗，实验中把４０只Ｗｉｓｔａｒ大鼠分为镉，镉锌，镉硒，镉锌硒及对照共五组，观察指标为大鼠体重变化；血清，镉，硒，锌；尿：镉，硒，锌；尿蛋白及血清碱性磷酸酶（ＡＫＰ），结果进行统计学处理后表明：加入锌，硒后，镉中毒的大鼠体重回升，血镉下降，尿蛋白下降，血清ＡＫＰ回升，尿镉排出增加，提示锌，硒对镉中毒表现有拮抗作     

Selenium kidney/liver ratios in rock squirrel populations from grassland and pinyon-juniper ecosystems

Selenium levels in liver and kidney tissues were determined for rock squirrels (Spermophilus variegatus) trapped within a distinct elevational gradient (grassland to pinyon-juniper ecosystem; alkaline to acidic soil) within the confines of the Kirtland Air Force Base Military Reservation in central New Mexico. Selenium levels in tissues were determined by graphite furnace atomic absorption spectrophotometry. Selenium kidney/liver ratios determined for rock squirrels decreased as elevational gradient increased (r = ?0.9403) in the pinyon-juniper ecosystem and increased as elevational gradient increased in the grassland ecosystem (r = 0.9493). Other tests of significance (t test, α 0.05) also support the inverse relationship between selenium kidney/liver ratios in grassland and pinyon-juniper ecosystems.     

Protective effects of selenium (Se) and zinc (Zn) on cadmium (Cd) toxicity in the liver of the rat: Effects on the oxidative stress

Cadmium (Cd) is a very harmful environmental pollutant that transfers between various levels of the food chain. To study the protective effect of Se and Zn on Cd-induced oxidative stress in livers, male rats received either, tap water, Cd, Cd+Zn, Cd+Se or Cd+Zn+Se in their drinking water, for 35 days. The activities of total superoxide dismutase (SOD), copper, zinc-superoxide dismutase (CuZn SOD), glutathione peroxidase (GPx) and catalase (CAT), malondialdehyde (MDA) level and the ratio of CuZn SOD to GPx activity, were determined in the liver. Exposure to Cd lowered total SOD, CuZn SOD, GPx and CAT activities, while it increased MDA level and the ratio of CuZn SOD to GPx activity, in the organ studied. With Se or Zn administration during exposure to Cd, only partial corrective effects on Cd-induced oxidative stress in the liver have been observed, while Se and Zn together assured a more efficient protection of the organ against the observed oxidative stress.     

RNA/DNA ratios as a sublethal endpoint for large-scale toxicity tests with the nematode Caenorhabditis elegans

Caenorhabditis elegans increasingly is attractive as a toxicity test organism, particularly as a model system to study mechanisms of toxicity at a molecular level and the way that these lead to whole organism and population level effects. Inhibitions of growth, reproduction, movement, and feeding rate all have been proposed as sublethal toxicity endpoints. These endpoints are more sensitive than 24-h acute toxicity endpoints, but assays are much more time consuming, making them difficult to use in mass screening. The RNA/DNA ratio, after 48-h exposure to metals, has median effective concentration (EC50) values of 0.05, 0.6, 6.1, and 35 mg/L for Cu, Pb, Cd, and Zn, respectively. This makes it a slightly more sensitive toxicity endpoint than reduction of individual growth after 72-h exposure to the same concentrations. This facilitates the near-simultaneous assessment of sublethal toxicity in many nematode samples. The constant cell number of C. elegans means that different stages in the life history have very different RNA/DNA ratios even in the absence of toxins. So, RNA/DNA ratios can be used only on prereproductive, age-synchronized cultures. Assessing the sublethal toxicity of metals to C. elegans shows that it is sensitive particularly to Cu.     

Fate and toxicity of temephos applied to an intertidal mangrove community

The distribution, persistence, and toxicity of the mosquito larvicide temephos was monitored following aerial applications to an intertidal mangrove community in Lee County, Florida. The amount of temephos penetrating to the mangrove floor ranged from 15 to 70% of the amount entering the upper leaf canopy, with 50-60% of that applied remaining on the mangrove leaves. Rainfall caused an additional influx of temephos from the leaves to the mangrove floor. Residues were detected in intertidal water at 2 h, but not 4 h after application. However, temephos was observed to persist in simulated tidal pools and on mangrove leaves for up to 72 h and in oysters for up to 48 h after application. Marine organisms placed in cages at 3 test sites and a control site were monitored for toxic effects. Mortality among natural mosquito larvae was simultaneously monitored. Mysids (Mysidopsis bahia) exhibited a significant mortality at one site during 1 of 3 applications monitored; however, no correlation was observed between mortality and temephos concentration in water. No significant mortality was observed for the other organisms, which included: brown shrimp (Panaeus aztecus), grass shrimp (Palaemonetes pugio), juvenile snook (Centropomis undecimalis) and sheepshead minnow (Cyprinodon variegatus).     

Fate of mirex-14C in the rat and plants

Summary About 58.5 percent of the uniformly labeled mirex-¹⁴C administered to rats as a single oral dose was excreted in feces and 0.69% in urine after 7 days. Considerable tissue storage of mirex was observed; fat, muscle, liver, kidneys and intestines contained 27.8, 3.20, 1.75, 0.76 and 0.23 percent of the total dose, respectively 7 days after treatment. While the first half-life of mirex was 38 hours, the projected second half-life was in excess of 100 days indicating a very slow rate of elimination from the body. No metabolite of mirex was detected in the feces, urine or any of the tissues. Nor was any mirex metabolite detected on incubation with rat, mouse, and rabbit liver preparations or plant root preparations. Mirex was concentrated by pea and bean roots and smaller amounts were translocated to the aerial parts when the plants were allowed to grow in water containing 1, 5 and 10 ppm mirex for 2 days. The resistance of mirex to biodegradation and its long biological half-life indicate that this insecticide may have an environmental half-life which far surpasses that of any previously studied insecticide.     

Cadmium, zinc, and copper in rabbit kidney metallothionein--relation to kidney toxicity

Twenty-two rabbits were given repeated subcutaneous injection of cadmium chloride. The cumulative cadmium dose given ranged from 13 to 214 mumole/kg body weight. Five rabbits served as controls. The treatment resulted in cadmium concentrations in kidney cortex that ranged from 0.3 to 3.2 mmole Cd/kg and a subsequent production of metallothionein. The molar ratio of cadmium, zinc, and copper in metallothionein fractions from kidneys with different concentrations of cadmium was determined. At low concentrations of cadmium in rabbit kidneys, zinc was the dominating metal bound to metallothionein (70-90%). At high concentrations of cadmium in kidneys, cadmium was the dominating metal in metallothionein. Evidence of kidney toxicity, in the form of beta2-microglobulinuria, was seen when cadmium constituted 85% of the metal ions recovered from metallothionein fractions. The remaining 15% was zinc. This indicates that at most six of the seven metal-binding sites in mammalian metallothionein are occupied by cadmium and that the remaining site is occupied by zinc. Our data provide further support for the hypothesis that chronic cadmium nephrotoxicity develops when there is a lack of metal-binding sites available for cadmium in metallothionein.     

Cd and Zn in atmospheric deposit, soil, wheat, and milk

Continuous air quality monitoring in the Vojvodina district of Serbia and Montenegro has shown high levels of Cd, especially in the outskirts of large towns such as Kikinda. The construction and metal processing industries located in Kikinda have been emitting significant amounts of heavy metals into the environment. The levels of Cd and Zn were monitored in the region of Kikinda and compared to their concentrations detected in Novi Sad, the capital of Vojovodina, where emission of heavy metals originated mostly from vehicle traffic. The study was performed during the economic sanctions when industrial production decreased drastically. The consequence of that was a significant decrease of the concentration of Cd and Zn in atmospheric deposits. Data collected during 3 years indicated a direct influence of atmospheric deposits on heavy metal distribution in the chain soil-cattle feed-milk. Decreased Cd concentrations of 93% in atmospheric deposits in the Kikinda region resulted in decreased Cd concentrations of 17% in cattle feeds and 13% in milk. Decreased Zn concentrations of 58% in atmospheric deposits caused reduced Zn concentrations of 30% in soil, 17% in cattle feeds, and 17% in milk.     

Fate of the mushroom hydrazine agaritine in the rat and mouse

The fate of the mushroom hydrazine [14C]agaritine was investigated in the mouse and rat strains previously employed in carcinogenicity studies with the edible mushroom Agaricus bisporus. Agaritine was rapidly absorbed in both species, achieving higher blood levels in the mouse, but with similar area under the curve. Covalent binding of agaritine material to proteins was detected only in the liver and kidney, but the extent of binding was the same in the rat and mouse. Most of the radioactivity was excreted during the first 24 hours in both animal species: in the rat it was distributed equally between urine and feces, whereas in the mouse more of the radioactivity was excreted in the urine. No qualitative differences in the metabolic profile were evident, but quantitative differences were observed. Treatment of the urine with deconjugating enzymes did not reveal the presence of any conjugates. Agaritine, N'-acetyl-4-(hydroxymethyl)phenylhydrazine, and 4-(hydroxymethyl)benzene diazonium ion were not detected in the urine or in the plasma of either species. No mutagens or promutagens were detected by the Ames mutagenicity assay in the urine of either species after exposure to agaritine. Repeated administration of agaritine to rats and mice did not alter the urinary metabolic profile and excretion of radioactivity. Similarly, feeding mice a raw mushroom diet, according to the protocol employed in the carcinogenicity studies, did not modulate the excretion of radioactivity or the urinary metabolic pattern. No major species differences in the fate of agaritine in rat and mouse were noted that could provide a rationale for the carcinogenicity of A. bisporus in the mouse, but not in the rat.     

Relationships between Cd and Zn partitioning and geochemical composition in sediments from Chinese rivers

Adsorption isotherm experiments were conducted to determine the distribution coefficients (Kd) for Cd and Zn between water and sediments from twelve rivers in eastern China. The low metal concentration (<10(-10) M) added into the sediment-water system enabled the direct measurements of linear adsorption isotherms. When other solution parameters, such as ionic strength, were controlled, sediment geochemical characteristics were the major factors affecting metal distribution. The Kd was highly dependent on the total organic carbon contents and Fe-Mn oxide at pH = 7.0, and was affected significantly by the carbonate content in the sediments due to its control of pH. The Kd of the Huanghe sediments, which had the highest carbonate concentration (13.1%), increased sharply for both Cd and Zn when the pH increased. A quantitative model using the experimentally obtained phase distribution coefficients (Kd)i was applied to study the effects of different geochemical phases in the sediment on metal distributions. The (Kd)i of carbonate was correlated significantly with the carbonate content in the sediment, whereas the (Kd)i of total organic carbon (TOC) and Fe-Mn oxide phases were highly pH dependent. Using the (Kd)i for each geochemical phase, the calculation showed that about 91% and 85% of sorbed Cd and Zn, respectively, added to the batch reactors were distributed among the three major geochemical phases: TOC, Fe-Mn oxide, and carbonate. Total organic carbon was the most important binding phase for Cd, and Fe-Mn oxide for Zn. Furthermore, adsorption experiments with simulated sediments show the importance of interactions between different geochemical phases on metal partitioning.     

Determinants of variability in acute to chronic toxicity ratios for aquatic invertebrates and fish

Variability in acute to chronic ratios (ACRs; median lethal or effect concentration divided by chronic value) has been of continuing interest in aquatic toxicology because of the reliance on ACRs to estimate chronic toxicity for chemicals and species with known acute toxicity data but with limited or no information for chronic toxicity. To investigate the variability and significant differences in ACRs, an extensive data set was compiled of 456 same-species pairs of acute and maximum acceptable toxicant concentrations for metals, narcotics, pesticides, and other organic chemicals. The overall median value for 456 aquatic invertebrate and fish ACRs analyzed in the present study was 8.3, with a 16,000-fold range in values (1.1-18,550) and a 32-fold range in 10th and 90th percentile values (2.5-79.5). Median ACRs for taxa, ambient habitat media, chronic test end point, and chemical mode of action (MOA)/class categories generally were similar but, in some cases, extremely variable (ranges of 1 to >10,000). No significant differences (p 相似文献