Relative in vitro affinity of hepatic metallothionein for metals

The ability of selected metals (Ag, Al, As, Ca, Cd, Co, Cr, Cu, Fe, Hg, Mg, Mn, Mo, Ni, Pb, Tl and V) to displace Zn from Zn-metallothionein (Zn-MT) was quantitated. Of the metals tested Cd had the highest affinity for MT, with 1.33 microM displacing 50% of the 65Zn bound to MT (EC50), followed by Pb (1.46 microM), Cu (1.93 microM), Hg (3.93 microM), Zn (8.06 microM), Ag (10.4 microM), Ni (474 microM) and Co (880 microM). As, Ca and Mo had a limited ability to displace Zn from MT while Al, Cr, Fe, Mg, Mn, Tl and V had no effect on Zn binding even at 1.0 mM.     

Effects of various trace metals on the binding of cadmium to rat hepatic metallothionein determined by the Cd/hemoglobin affinity assay

The Cd/hemoglobin affinity assay is finding increasing use as an indicator of metallothionein in a variety of biological tissues. Because the assay relies on the ability of heat-stable proteins to bind Cd, it is important to know the relative affinities of different trace metals to bind to such proteins, relative to Cd. This study examines the ability of 15 trace metals to prevent the binding of Cd to metallothionein using the Cd/hemoglobin affinity assay for metallothionein. Cd, Cu, Hg, and Ag were the only metals tested which significantly inhibited the binding of a fixed concentration (2 microM) of 109Cd to a crude preparation of rat hepatic metallothionein. As, Co, Cr, Fe, Mn, Mo, Ni, Pb, Sn, Th, and Zn had no inhibitory effect at the highest concentrations tested. However, As, Sn, Th, and Zn prevented the precipitation of hemoglobin at relatively low concentrations and, thus, could not be fully tested for inhibitory potency. Cu was the most potent inhibitor, producing more than 90% inhibition at 5 microM, followed by Ag, Hg, and Cd, which produced 76, 72, and 65% inhibition of cadmium binding at 5 microM, respectively. These results suggest that caution should be taken in interpreting metallothionein concentrations obtained by the Cd/hemoglobin affinity assay in tissues which contain relatively a high concentration of Cu, Ag, or Hg, relative to that of Cd.     

Lead and other metals can substitute for Ca2+ in calmodulin

We have studied the interaction between some heavy metal ions, as compared with earth alkali ions, and calmodulin, a tissue protein which binds Ca2+ and mediates some of its effects. 1. Calmodulin dependent phosphodiesterase was activated with Pb2+, Ca2+, Sr2+, Ba2+, and Cd2+ (EC50 about 0.8 microM). The maximal activation achieved decreases in the order given. Hg2+, Sn2+, Fe2+, Cu2+, Ni2+, Bi3+, and Sb3+ up to 20 microM did not activate. 2. Pb2+ can replace Ca2+ with respect to the calmodulin-dependent phosphorylation of brain membranes. With high Pb2+ concentrations, phosphorylation was inhibited. 3. Calmodulin binding to brain membranes was enhanced with concentrations below 10(-4)M in the following order: Pb2+ greater than or equal to Ca2+ approximately Sr2+ greater than Cd2+ greater than Mn2+ greater than Ba2+. In contrast Mg2+, Hg2+, Sn2+, Fe2+, Ni2+, Co2+, and Cu2+ triggered, if at all, a non-saturable binding of calmodulin. 4. In the flow-dialysis, other ions competed with 45Ca2+ binding to calmodulin in the following order: Pb2+ approximately Ca2+ greater than Mn2+, Ba2+, Cd2+, Sr2+. Thus among the ions investigated Pb2+ is a fully potent substitute for Ca2+ in every calmodulin-dependent reaction investigated. Cd2+ is always much less potent. The earth alkali ions Sr2+ and Ba2+ take an intermediate position. It remains to be shown whether calmodulin is merely a storage site for Pb2+, or whether the resulting functional changes play a role in Pb2+ poisoning.     

Dose-response effects of various metal ions on rat liver metallothionein,glutathione, heme oxygenase,and cytochrome P-450

Adult male rats received ip injections of the maximum tolerable dose (MTD; μmol/kg/day, in parentheses following metal), or a fraction thereof, of Hg (5), Cd (20), Se (25), Ag (65), Cu (75), Co (100), Ni (120), Zn (200), Mn (250), Fe (300), Pb (400), or Cr (400) 36 and 12 hr before sacrifice. MTDs were estimated from previous studies, and at least three serial dilutions ($\text{1}\text{2}$, $\text{1}\text{4}$, $\text{1}\text{8}$, etc.) of the MTDs were tested for each metal. The effects of metal treatment on hepatic heme oxygenase activity (HO), cytochrome P-450, reduced glutathione (GSH) and metallothionein (MT), and renal MT and GSH were determined. Nine metals increased HO at the MTD, but only Cd, Se, Mn, and Pb increased HO at lower doses. These four metals plus Ag and Cr depressed cytochrome P-450 levels at the MTD, but only Cd, Mn, and Pb depressed cytochrome P-450 at a lower dose. Se increased hepatic GSH at the two highest doses, but all other metals had little or no effect. Kidney GSH was increased by all metals except Cd, Ag, Cu, and Cr, to a maximum level of only 150% of control (Pb). Cd and Zn induced hepatic MT in a dose-related manner to 420 and 580% of control, respectively. On a molar basis, Cd was about eight times more potent than Zn in increasing hepatic MT concentration. Hg, Ni, Mn, Fe, Pb, and Cr also significantly increased hepatic MT, but only to 150–200% of control. Pb had a slight but significant effect on hepatic MT at all doses down to 1/16th the MTD. This effect of PB, as well as other metals having a small effect on MT, may be the result of the effects of stress on MT rather than the metal ion per se. Renal MT was effectively induced by Hg, Cd, Cu, Ni, Zn, and Pb. Relatively small amounts of Hg (0.62 μmol/kg/day) significantly increased renal MT when compared to the minimum effective dose of Cd (10 μmol/kg/day) or Zn (50 μmol/kg/day). In conclusion, metals have a number of effects on potential hepatic and renal biochemical defense mechanisms. Most of the metals lacked specificity, affecting a number but not all of the parameters examined. However, of the 12 metals examined, Zn was the most selective in that it produced marked increases in MT and little or no effect on the other parameters, whereas Cd had the broadest effect, altering all parameters except GSH.     

The effect of cadmium and other metals on vascular smooth muscle of the dogfish shark, Squalus acanthias

The effect of Cd2+ and related metals (Ni2+, Hg2+, Pb2+, Co2+, Sn2+ Cu2+ and Zn2+) on vascular tension was studied using isolated rings of endothelium-free, smooth muscle from the ventral aorta of the shark, Squalus acanthias. Both Cd2+ and Ni2+ produced significant vasoconstriction at concentrations at or above 10(-6) M (112 and 59 ppb, respectively); the other metals were either marginally constrictive (Hg2+ and Sn2+) or were without effect (Pb2+, Co2+, Cu2+, and Zn2+). We suggest that previously published vascular effects of Hg2+ and Pb2+ may have been secondary to responses of the vascular endothelium, and that the role of Ni2+ in hypertension should be investigated further. Our data indicate that the effects of metals on this vascular smooth muscle are specific and not generic. Moreover, this system could be utilized to investigate the mechanisms of metal-induced vasoconstriction.     

Assessment of environmental contamination using feathers of Bubulcus ibis L., as a biomonitor of heavy metal pollution, Pakistan

Concentrations of metals such as Ca, Cd, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Ni, Pb, and Zn were analyzed in the feathers of cattle egret (Bubulcus ibis) from three breeding colonies in the Punjab province, Pakistan. The mean concentrations of Ca, Cd, Fe, Pb and Mn were significantly different between the three study sites (River Chenab, River Ravi and Rawal Lake Reservoir). The mean concentrations of Ca, Cd, Fe and Mn were significantly greater at the River Chenab heronry and Cr, Co, Zn, and Pb concentrations at the River Ravi heronry. The feathers of cattle egrets collected from the Rawal Lake Reservoir heronry were least contaminated. Multivariate statistical methods viz., Factor Analysis based on Principal Component Analysis (FA/PCA); Hierarchical Cluster analyses (HACA), and Correlation Analyses identified relatively similar associations of metals and their sources of input. Metals such as Ca, Mg, and K were related with natural input from parent rock material whereas trace metals viz., Cu, Cd, Co, Pb, Ni, and Zn were associated mainly with anthropogenic processes. Metals such as Fe, Mn, and Li were either correlated with natural input or with anthropogenic activities. Concentration of heavy metals such as Cd, Pb, and Cr were well above the threshold level that can cause adverse effects in birds and pose menace to the cattle egrets population in Pakistan. The study suggested that the feathers of cattle egret could be used as a bio-monitor of the local heavy metals contamination.     

Inter-element interactions in human hair

The concentrations of 33 elements: Ca, Mg, Na, U, Cu, Zn, P, Fe, Mn, Cr, Se, B, Co, Mo, Si, V, Ni, Be, Hg, Cd, Al, Pb, As, Ba, Au, Pt, Ag, Sr, Sn, Ti, W, Sb and Zr in hair were determined by inductively coupled plasma-mass spectrometry (ICP-MS) and inductively coupled plasma-atomic emission spectrometry (ICP-AES). Hair samples (n=83) were collected between 1996 and 2003 from inhabitants of city of Wroc?aw, located in Lower Silesia, south-west Poland (urbanized and industrialized region). Inter-element interactions were studied by evaluation of correlation coefficients between two elements, as well as by multiple regression analysis. The strongest relations found between the elements in the hair were as follows: Mg and Ca, Mn and Ca, Sr and Ca, Sr and Mg, U and Na, Ni and Zn, Mn and Sr, Cd and Ni, Sb and Pt. We obtained also the following essential linear multiple dependences (p<0.05): Al=f(U, P, Mn), As=f(Zn, Fe) (Zn is negatively correlated, β<0), Cu=f(V), Fe=f(Mn, As), Mg=f(Ca), Ca=f(Mg, Ba), Ni=f(Zn, Cd), Sb=f(Pt, Sn, W) and Ti=f(Fe, Co). These relations can be useful in the explanation of relationships among the elements in man.     

Pharmacological characterization of Aristolochia clematitis L. growing in the Stavropol Region

The amino acid and elemental composition of birthwort (Aristolochia clematitis L.) plant species occurring in the Stavropol region has been studied. The analyses showed a high content of tyrosine in the above-ground parts and revealed the presence of 25 elements (K, Ca, P, Mg, Al, Fe, Na, Si, Mn, Zn, Cu, Ni, Cr, V, Li, As, Pb, Co, J, Se, Cd, Hg, Be, Sn, Ti), some of which belong to the group of toxic metals. The differentiation of various plant organs with respect to the accumulation of different groups of chemical elements is established. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 4, pp. 23–24, April, 2006.     

The effect of age, sex, smoking habit and hair color on the composition of hair

Hair samples (N=83) were collected between the years 1996 and 2003 from inhabitants of Wroc?aw, a city located in Lower Silesia, south-western Poland (urbanized and industrialized region). The concentrations of 33 elements: Ca, Mg, Na, K, Cu, Zn, P, Fe, Mn, Cr, Se, B, Co, Mo, Si, V, Ni, Be, Hg, Cd, Al, Pb, As, Ba, Au, Pt, Ag, Sr, Sn, Ti, W, Sb and Zr in hair were determined by inductively coupled plasma-mass spectrometry (ICP-MS) and inductively coupled plasma-atomic emission spectrometry (ICP-AES) techniques. The effect of age, sex, smoking habits and hair color on the elemental composition of hair was investigated. Also, the obtained results were compared with literature data. It was found that the composition of hair varied with age, sex, hair color and smoking habits. This concerned the majority of elements except Ti, Se, Mn, Ni, Hg, Cd, As, Co (in the case of effect of age), Al, Cd, Co (sex), Cd, K, Ag, Ca, Co, Be (smoking habit), P, Fe, Al, Mn and Cr (hair color). Therefore, reference values for the level of the remaining elements should be normalized according to age, sex, smoking habit and hair color. This would make hair analysis more reliable.     

Comparison of the effects of metals on cellular injury and lipid peroxidation in isolated rat hepatocytes

Various mechanisms, including increases in lipid peroxidation, have been proposed to account for metal-induced cellular injury. By comparing several metals in the same cell population, it is possible to determine whether a correlation exists between ability to produce cell injury and ability to alter parameters pertaining to a particular mechanism. Of particular interest in this study was the relation between metal-induced cytotoxicity and increases in lipid peroxidation. The effects of Cr, Mn, Zn, Ni, Pb, Se, V, Fe, Cd, Hg, Cu, at final concentrations of 1-1000 microM, on the viability of isolated hepatocytes were therefore examined by assessing the loss of intracellular K+ and aspartate aminotransferase (AST). Simultaneously, the ability of the metals to induce lipid peroxidation, as measured by an increase in thiobarbituric acid (TBA) reactants, was assessed. Hg and Cu required the lowest concentration to produce cellular injury, while Cd produced less dramatic changes in cell viability and Fe at 1000 microM produced only a small decrease in intracellular K+. The largest absolute increases in lipid peroxidation were found in the presence of V, followed by Fe and Hg, with Cd and Se causing the smallest increase in TBA reactants. These observations suggest that the lipid peroxidation associated with Cd and Hg is not necessarily responsible for the loss of cell viability induced by these two metals.     

中药马齿苋的微量元素测定

本文报道用原子吸收分光光度法及等离子体发射光谱法测定马齿苋中二十一种微量元素的结果。     

Inhibitory effects of metals on ATP-induced current through P2X7 receptor in NG108-15 cells

We investigated the effects of heavy metal ions on the ATP-induced nonselective cation current through P2X7 receptor (I(NS x P2X7)) in NG108-15 cells using the whole-cell patch-clamp technique. Cu2+ inhibited the I(NS x P2X7) most potently among the metal ions investigated. Other metals such as Ni2+, Cd2+, Zn2+ and Co2+ also inhibited the I(NS x P2X7) in concentration-dependent manners. The order of potency was Cu2+ > Ni2+ > Cd2+ > Zn2+ > Co2+ with IC50 values of 16 nM, 0.79 microM, 1.2 microM, 3.0 microM and 4.6 microM, respectively. Fe3+ (10 and 100 microM) and Mn2+ (10 microM) did not affect the INS P2X7. A high concentration of Mn2+ (100 microM) slightly inhibited the I(NS x P2X7). When the concentration-response curve of ATP was obtained in the presence of 3 and 10 nM Cu2+, the maximal response but not the EC50 value appeared to be reduced, suggesting that the inhibition is not competitive. These results suggest that under physiological and toxicological conditions, metal ions, such as Cu2+, Ni2+, Cd2+, Zn2+ and Co2+, may modulate P2X7 receptor channels as inhibitors.     

The interaction of cations with activity of soluble protein kinase C from mouse brain

The interaction of some cations with the enzymatic activity of soluble protein kinase C was determined in order to elucidate whether protein kinase C can be activated by other metal cations besides Ca2+. Protein kinase C was activated by Ca2+ and Sr2+ having EC50 values of nearly 10 microM and 200 microM, respectively. Ba2+ likewise activated protein kinase C but was less potent. Co2+, Ni2+ and Mn2+ had no activating effects on the activity in the absence of Ca2+, but was slightly reduced in the presence of Ca2+ (0.5 mM). Cations with ionic radii close to Ca2+ (0.99 A) inhibited the activity irrespective of the absence or presence of Ca2+. The order of potency is as follows: Hg2+ greater than Cd2+ approximately Cu2+ much greater than Sm3+ greater than Tb3+ greater than La3+. Pb2+ and Zn2+, which showed a high affinity to SH-groups, as well as Hg2+, Cd2+ and Cu2+, which also inhibited the activity. Thus, among the ions investigated, the alkaline-earth ions Sr2+ and Ba2+ could be substituted for Ca2+, irrespective of ionic radii. The serious environmental pollutants such as Hg2+, Cd2+ or Pb2+ impaired the activity of protein kinase C probably due to SH-blocking.     

ICP-AES/ICP-MS测定西藏和河南产藏红花中主要金属元素及重金属含量(英文)

建立了ICP-AES/ICP-MS测定西藏和河南产藏红花中19种元素含量的方法。19种元素包括主要元素Ca、Fe、Mg、P、Sr、Al、Mn、Zn、V、Cr、Se、Co、Ni、Mo和重金属As、Cu、Cd、Hg、Pb。对于所测元素,标准曲线的相关系数>0.9938,方法的相对标准偏差RSD<5.25%。结果表明,ICP-AES/ICP-MS可用于藏红花质量控制,并为西藏和河南产藏红花中元素的含量测定提供了方法。     

Selective oxidation of Zn2+ -insulin catalyzed by Cu2+

The purpose of this study is to quantitate the sensitivity of Zn2+ -insulin to oxidation catalyzed by various redox active transition metals, Cu2+, Fe2+, Mn2+, Ni2+, Co2+, Cr3+. Human recombinant insulin (INS) was subjected to oxidation under various conditions in the presence and absence of Zn2+ and ascorbate. The extent of oxidation was monitored by RP-HPLC. Only Cu2+, but none of the other metals or combination thereof, for example, Ni2+/Co2+, Co2+/Cr3+, and Ni2+/Cr3+, catalyzed INS oxidation, for example, to an extent of 45% when 20 microM INS/8.8 microM Zn2+ were exposed to 8 microM Cu2+ and 50 microM ascorbate for 90 min. The Cu2+ -catalyzed oxidation mainly targeted the B chain of INS, where the two histidine residues are located.     

Inhibition by cations of antagonist binding to histamine H1-receptors: differential effect of sodium ions on the binding of two radioligands.

1. Measurements have been made of the inhibition by mono- and divalent cations of the binding of [3H]-(+)-N-methyl-4-methyldiphenhydramine ([3H]-QMDP) to histamine H1-receptors in homogenates of guinea-pig cerebellum. 2. The binding of [3H]-QMDP was inhibited by monovalent cations with an order of potency Li+ = Na+ greater than K+ greater than Cs+ = Rb+. The IC50 for Li+ was 39 mM, but that for K+ was 132 mM. Hill coefficients for inhibition curves for Li+ and Na+ were less than 1. 3. Divalent cations also inhibited the binding of [3H]-QMDP. The most potent cations examined were Hg2+, Cd2+ and Zn2+, with IC50 values of 5, 17 and 41 microM, respectively. Ca2+ and Mg2+ were relatively weak inhibitors (IC50 12 and 34 mM, respectively). The potency of Ni2+, Co2+ and Mn2+ was intermediate between these groups. Hill coefficients for inhibition curves for Hg2+, Cd2+ and Zn2+ were greater than 1, but Hill coefficients for the other cations were less than 1. 4. Both mono- and divalent cations also inhibited the binding of [3H]-mepyramine. The divalent cations were approximately equipotent in inhibiting the binding of [3H]-QMDP and [3H]-mepyramine. The same was true for Li+. However, Na+ was markedly more effective against [3H]-QMDP binding than against the binding of [3H]-mepyramine. 5. The effect of 40 mM Li+ on the parameters of binding of [3H]-mepyramine was to increase the best-fit value of the concentration giving half-maximal binding EC50, by approximately 2 fold without having any significant effect on the maximum amount of binding.(ABSTRACT TRUNCATED AT 250 WORDS)     

A study on metals content in patients with colorectal polyps

Data on metals involvement in colorectal polyps are scarce and fragmentary. The aim of this study was to examine whether the level of metals could be associated with risk of colorectal polyp development. The concentration of 15 chemical elements (Al, Ba, Ca, Cd, Co, Cr, Cu, Fe, Hg Mg, Mn, Pb, Se, Sr, and Zn) in 17 colorectal biopsies of healthy individuals, in 15 polypotic and corresponding nonpolypotic biopsies taken from the same individual, was evaluated. Concentration in polyps of metals such as Al, Ca, Mg, Mn, Pb, Sr, and Zn was unchanged both in unpaired and paired samples; elements such as Ba, Cd, and Hg were significantly lower and Fe was significantly higher both in individual and paired tissues. Cobalt, Cr, and Cu were significantly different only between polyps and the adjacent normal tissue area; Se showed a significant accumulation comparing polyps versus healthy tissues. The difference found in some elements between polyps and a control tissue provides an indication about the role of essential and nonessential elements in the early stage (polyps) in the colon carcinogenic process and encourages further studies to confirm the involvement of such elements in neoplastic processes.     

Hypothermia and hypometabolism: sensitive indices of whole-body toxicity following exposure to metallic salts in the mouse

To investigate the practicality of hypothermia and hypometabolism as sensitive indices of toxicity in the mouse, oxygen consumption was monitored continuously and body temperature was measured at 30 min postinjection following the intraperitoneal administration of various metal salts. Eleven metal ions were tested: Al3+, Cd2+, Co2+, Cr2+, Cu2+, Hg2+, Mg2+, Mn2+, Ni2+, Pb2+, and Zn2+. All metals induced dose-dependent reductions in both oxygen consumption (hypometabolism) and deep body (colonic) temperature. Comparative toxicity of the metal ions was evaluated by calculating the dose of metal ion in dimensions of mmol/kg body mass needed to reduce colonic temperature to 35 degrees C. The order of toxicity from lowest to highest was as follows: Cr less than Al less than Pb less than Mn less than Mg less than Zn less than Cu less than Co less than Ni less than Hg less than Cd. The threshold doses for reducing body temperature were less than 5% of the LD50 in 6 of the metals studied. Metal salts with relatively low LD50 doses such as Hg, Cd, and Ni were most efficacious in inducing hypothermia and hypometabolism. Moreover, there was a direct linear relationship between dose for inducing hypothermia or hypometabolism and the reported LD50. Hence, the hypothermia and hypometabolism test may prove to be a sensitive and rapid test for the evaluation of toxicity of environmental contaminants.     

不同产地当归中金属微量元素的比较研究

目的：对不同产地当归中金属微量元素的含量进行初步的比较研究。方法：样品经微波消解后,以铟（In）元素为内标,利用电感耦合等离子体质谱（ICP-MS）测定不同产地的当归中Be、B、A l、V、Cr、Mn、Fe、Co、N i、Cu、Zn、As、Se、Cd、Ba、Hg和Pb等17种微量金属元素的含量。结果：该方法对各元素的检测线为0.003~2.478 ng/g,加样回收率为82.3%~112.2%,标准物质杨树叶的测定值与标示量基本吻合。结论：所建立的方法快捷,准确、灵敏度高,可以用于测定当归中金属的微量元素的含量,不同产地的当归其所含金属微量元素有很大不同,如某地产的当归有些元素含量明显高于其他地方。     

Evidence of species-specific detoxification processes for trace elements in shorebirds

This study investigated sub-lethal effects and detoxification processes activated in free-ranging Red Knots (RKs) (Calidris canutus) from the Pertuis Charentais on the Atlantic coast of France, and compared the results with previous data obtained on another shorebird species, the Black-tailed Godwit (Limosa limosa). The concentrations of 13 trace elements (Ag, As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se, Zn) were assessed in the liver, kidneys, muscle and feathers. Stable isotope analyses of carbon and nitrogen were carried out to determine whether differences in diet explained variations in elemental uptake. The mRNA expression of relevant genes (cytochrome c oxidase 1, acetyl-CoA carboxylase, Cu/Zn and Mn superoxide dismutase, catalase, metallothionein, malic enzyme), antioxidant enzyme activities (catalase, glutathione peroxidase (GPx), superoxide dismutase), and metallothionein (MT) levels were investigated to shed light on trace element detoxification and toxic effects. Although Red Knots were characterized by elevated As and Se concentrations which were potentially toxic, most elements were usually below toxicity threshold levels. The results strongly suggested a dietary specialization of Red Knots, with individuals feeding on higher trophic status prey experiencing higher As, Hg and Se burdens. Red Knots and Godwits also showed discrepancies in elemental accumulation and detoxification processes. Higher As and Se concentrations in Red Knots enhanced catalase gene expression and enzyme activity, while Godwits had higher Ag, Cu, Fe and Zn levels and showed higher MT production and GPx activity. The results strongly suggest that detoxification pathways are essentially trace element- and species-specific.