Non-essential Trace Metals Research Articles

Chapter 20: An approach to study of transport of trace metals at the blood-brain barrier

Certain trace metals have important influences on brain development and function. Zinc, iron and copper are essential in very small amounts but may be toxic at high concentrations. Other metals—for example, lead, aluminium, and mercury, have no known normal role, but even at low exposures may cause defects in brain development and function or even degeneration. Either to produce physiological or pathophysiological effects on the brain, the metal must traverse the blood–brain barrier (BBB) to act directly on the neurones or glial cells, or alternatively it could have an indirect influence. The latter could occur by an extracerebral metabolic effect altering the level of a product or products that itself enters brain and is active on it. The trace metal might also have an indirect effect by influencing the transport or regulation of another substance at the BBB. It is apparent that lead and several other trace metals cross the BBB quite readily. There may be specific ion channels or transporters for essential trace metals. Nonessential trace metals that enter brain might be anticipated to utilize mechanisms that normally handle essential cations or anions.

Interaction between essential elements - zinc and iron and metal pollutants - cadmium and lead on cell division and chromosome aberrations in Vallisneria spiralis L.

The cytotoxic effects of cadmium and lead: non-essential trace metals in combination with important trace elements-zinc and iron respectively were studied on cell division and chromosomal aberrations in leaf-tip cells of Vallisneria spiralis L., a submerged aquatic plant. The results showed that the toxic effects of lower concentrations of heavy metal lead, with respect to the parameters mentioned, could be antagonised by the essential metal iron. Zinc, on the other hand, further accentuated the effect of cadmium: the frequency of dividing cells decreased and the percentages of chromosomal aberrations were significantly high in the combination sets.

Correlation between some selected trace metal concentrations in six species of fish from the Arabian sea

The role of trace metals in marine ecosystems has been keenly investigated during recent years. It is known that abundance of essential trace metals regulates the metal content in the organisms by homeostatic control mechanisms, which when cease to function cause essential trace metals to act in an either acutely or chronically toxic manner. Therefore, a correlation study based on essential and non-essential trace metal concentrations is imperative for extending the existing knowledge of bioaccumulation of trace metals in marine organisms. An attempt has been made in the present investigation to bring out quantitative correlations between the concentrations of iron, copper, lead and zinc in the edible muscle tissue of six species of marine fish: Salmon (salmon sole); tuna (thunnus thynnus); pomfret silver (pampus argenteus); Pomfret black (formioniger); long tail tuna (thynnus tonggel) and Indian oil sardine (sardinella longiceps). These fish are abundantly available in Pakistan along the coastal line of the Arabian Sea and have great commercial value. The computational analysis on the trace metal correlation was conducted using an MSTAT statistical package.

Comparative study of the patterns of bioaccumulation of essential (Cu, Zn) and non-essential (Cd, Pb) trace metals in various estuarine and coastal organisms

The patterns of accumulation of essential and non-essential trace metals have been studied comparatively in worms, molluscs, crustaceans, and fish exposed to short-term experimental contaminations and low chronic contaminations in a polluted environment. In short-term contaminations, the concentrations X of the non-essential metals cadmium and lead in the organisms depend mainly on their environmental level Y according to the power function Y = aX b . For copper - an essential metal - this equation is also suitable to describe the bioaccumulation in some species ( Nereis diversicolor O.F. Müller, Scrobicularia plana (da Costa), Gammarus zaddachi Sexton) for a large range of experimental overloads. As for the mussel Mytilus edulis L., this equation is accurate for medium or high overloads only. All the species are able to control the level of the essential zinc in their tissues but for both copper and zinc the best regulators are the more highly evolved forms including decapod crustaceans and fish. The in situ chronic contaminations support the same conclusions. In one fish and one decapod crustacean species it has been shown that the regulation mechanisms may be functional since early life stages. When the duration of exposure to essential metals increases, the regulation mechanism is, however, disturbed by more and more low additional concentrations in sea water.

Spectroscopic studies and characterization of metallothioneins containing mercury, lead and bismuth

Metallothioneins are widely distributed metal-binding proteins which are involved in the metabolism, ▪ storage and detoxification of essential and nonessential trace metals. The vertebrate forms characterized to date contain a single polypeptide chain of 61 amino acid residues, among them 20 cysteines providing the ligands for 7 metal-binding sites. Native metallothioneins are usually heterogenous in metal composition with Zn, Cd, Cu and occasionally other metals occurring in varying proportions [1]. However, forms containing only a single metal species, i.e., Zn, Cd, Ni, and Co, have been prepared by reconstitution from the metal-free apoprotein [2, 3]. By spectroscopic analysis of such derivatives it was established unambiguously that all cysteine residues provide their thiolate ligands for metal binding, that each metal ion is bound to 4 thiolate ligands that the symmetry of each complex is tetrahedral, and that in order to satisfy the requirements of the overall Me 7(Cys −) 20 stoichiometry, these ceomplexes are combined to form metal-thiolate clusters [4]. Mercury and bismuth are also occasional constituents of native metallothionein [5]. To explore the mode of binding of these and related ions, we have now prepared derivatives containing Hg(II), Pb(II) or Bi(III). With Hg(II) and Pb(II) different types of complexes are formed depending on pH and metal-to-protein ratio. At a stoichiometry of 7 metal ions per molecule with each of the three metals unique complexes are obtained in which all cysteine residues are likely to participate in metal binding. The absorption, circular dichroism (CD) and magnetic circular dichroism (MCD) spectra of these forms are highly characteristic (Fig. 1) and can be interpreted in terms of Jørgensen's optical electronegativity theory of electron transfer (CT) transitions of metal ligand complexes [6]. From the coincidence of the location of the first CT-transition of Hg 7- and Pb 7-metallothionein with those predicted theoretically for T d-thiolate coordination of these metals, it appears very likely that in these derivatives of metallothionein, too, these metals are bound in T d microsymmetry. The close similarity of the spectra of Bi 7- and Pb 7-metallothionein allows, furthermore, the inference that Bi(III) which is isoelectronic with Pb(II) is also bound in this fashion. Since T d coordination is highly unusual for these metals, it appears that as in the earlier case of Ni 7-metallothionein [3], this geometry is imposed by the rigidly maintained thiolate-binding sites of the protein. That all three derivatives have the same overall structure is suggested independently by the observation that their Stoke' radii are identical.

Metallothionein: A diamagnetic metalthiolate cluster protein

Metallothionein (MT) is an ubiquitously occurring, extremely sulfur- and metal-rich protein (mol. wt 6–7000) which plays a role in the metabolism and the detoxification of several essential and nonessential trace metals. All mammalian forms consist of a single polypeptide chain with a total of 61 amino acid residues of which 20 are cysteines. Each molecule binds 7 bivalent metal ions, most commonly Zn(II) and Cd(II). All cysteine residues participate in metal coordination through formation of metalmercaptide bonds. Their position in the polypeptide chain is preserved in all mammalian forms. Unique features are the CysXCys sequences (where X stands for an amino acid other than Cys) occurring 7 times along the chain. MT is an elongated nonglobular protein with an axial ratio of about 6 [1, 2]. As documented by 1H NMR and IR spectroscopy, it is a compact molecule with some secondary structure; however, it has not been crystallized as yet [3]. Hence, detailed structural information comes exclusively from spectroscopic studies. The electronic absorption spectrum is dominated by contributions from the electron transfer transitions of the metalthiolate complexes superimposed upon the plain absorption spectrum of the polypeptide chain. The positions of the first electron transfer band are strongly metal-dependent. The locations displayed in the derivatives of MT containing Zn, Cd, Hg or Pb are in accordance with Jørgensen's optical electronegativity scale. They coincide very closely with the shifts predicted for tetrahedral tetrathiolate model complexes, thus suggesting the same metal coordination in MT [4]. This is corroborated by the spectroscopic properties of MT reconstituted with Co(II). The visible and near-IR absorption spectrum of the green-colored derivative shows, besides the Co(II)thiolate electron transfer bands, dd maxima at 600, 682 and 743 nm belonging to the ν 3[ 4A 2 → 4T 1(P)] transition and at 1230 nm belonging to the ν 2[ 4A 2 → 4T 1(F)] transition. These are diagnostic of distorted tetrahedral tetrathiolate high-spin Co(II) complexes, a conclusion further substantiated by the magnetic circular dichroism (MCD) and electron spin resonance (ESR) spectra [5]. Independent evidence for the tetrahedral structure is also available for Zn(II)MT based on extended X-ray absorption fine structure (EXAFS) measurements [6] and for Cd(II)MT based on perturbed angular correlation of gamma ray (PAC) ▪ measurements using MT which contains the shortlived excited isomer 111mCd(II) [7]. The involvement of four sulfur ligands in the coordination of each metal ion is reconcilable with the overall Me(II) 7(Cys −) 20 stoichiometry of the molecule only if the metal complexes are sharing some thiolate ligands, thereby forming metal-thiolate clusters. This conjecture is now also confirmed experimentally. Thus the partitioning of the metal-coordinating ligands into bridging and non-bridging (terminal) thiolate ligands is manifested in a substantial broadening of the sulfur core electron binding energy profile in the X-ray photoelectron spectrum (ESCA) of MT as compared to those of elemental sulfur or monothiols [3]. Direct proof for clustering of the metal centers comes from the demonstration of metalmetal interactions by magnetic resonance spectroscopy. Thus in 113Cd-enriched MT 113Cd NMR resonances are split into multiplets by 113Cd 113Cd scalar coupling [8] and in fully substituted Co(II)MT the ESR-resonances are largely suppressed due to antiferromagnetic spin-canceling. This latter effect is also confirmed by magnetic susceptibility measurements [9]. By monitoring the changes in ESR amplitude and in magnetic susceptibility attending the stepwise incorporation of Co(II) into the protein, it is moreover possible to follow the building-up of the cluster structure. This process is biphasic. Up to binding of 4 equivalents of Co(II) the paramagnetic signals increase as expected for magnetically noninteracting high-spin complexes. However, upon further addition of Co(II), these features are lost again, signalling the transition to the magnetically interacting oligonuclear structures [9]. This two-step mode of metal-binding in which separate Co(II) tetrathiolate complexes are formed first is compatible with the model of two separate metal-thiolate clusters in MT deduced for 113Cd NMR homonuclear decoupling experiments [10] and from proteolytic cleavages studies [11] as well as from a 113Cd NMR study on cluster formation in progress in this laboratory. However, the actual steric organization of these clusters remains to be determined. An attractive structure consistent with all spectroscopic information at hand is the cage-like adamantane decahedron built up of thiolate units of tetrahedral symmetry (Fig. 1). The remarkable simplicity of the spectra and the unique capacity of MT to accommodate stoichiometrically different paramagnetic and diamagnetic metal ions, i.e., Ni(II), Co(II), Zn(II), Cd(II), Hg(II), Pb(II) and Bi(III), and to force them into environments of tetrahedral microsymmetry could be optimally accounted for by such a model or a variation of it. The need for these regular bioinorganic structures in MT would explain the remarkable preservation of the positions of all cysteine residues throughout mammalian evolution.

The Importance of Cadmium as a Factor in Calcified Upper Urinary Tract Stone Disease-a Prospective 7-year Study

The non-essential trace metal cadmium may cause major pathological effects on the kidneys. A group of coppersmiths who have been chronically exposed to cadmium poisoning was systematically studied over a 6-year period. The stone prevalence in the group is now just under 40% as compared with 3.5% in a general population. The blood cadmium levels have remained persistently elevated despite removal of the cadmium source. The measurement of cadmium as a means of monitoring chronic poisoning has been undertaken in terms of the prospective study in the coppersmiths and also in its relationship to other trace metals, namely serum zinc and copper. Urologists should be aware of the possibility of cadmium poisoning.

Uptake of Cadmium and Lead by a Rooted Aquatic Macrophyte (Elodea Canadensis)

The role of roots in the uptake of nonessential trace metals by aquatic macrophytes was investigated Elodea canadensis. Plants were grown in 2 lakes in which metal concentrations in the water differed. Specimens in each lake were anchored in either control sediment or in sediment contaminated with Cd and Pb. Plants grown in the same water but in sediment from different sources had significantly different concentrations of the 2 metals. Elodea samples rooted in sediments from the same source but grown in water with different levels of metals also accumulated significantly different amounts of Cd and Pb. Thus the importance of both sediment and the surrounding water as sources of metals for aquatic plants was demonstrated. Samples grown in water and sediment containing low levels of metals had minimal concentrations of 0.32 mg/g Cd and 5.2 mg/g Pb, while plants grown in metal—contaminated water and sediment accumulated up to 32.33 mg Cd/g and 160.9 mg Pb/g.

The lead content of the trachea in Baltimore residents.

Lead is an ubiquitous environmental contaminate and, as a result, one of the most abundant nonessential trace metals in man. The lead content of human tissues has been determined by various researchers; however, only Tipton and Cook (1963) have reported the lead content of the trachea. Part of this study involved the determination of trachea lead in residents of Baltimore, Maryland, sampled prior to 1957. The communication presents the lead content of the trachea of seventeen Baltimore residents sampled in 1972. The lead content of these tissues are evaluated with particular reference to the lead body burden of Baltimore residents.

The lead content of the aorta in male residents of Baltimore, Maryland.

Lead is an ubiquitous environmental contaminant and as a result one of the most abundant nonessential trace metals in man. The lead content of human tissues has been determined by various researchers, however, only Tipton and Cook (1963) have examined the lead content of the aorta. In reviewing this work, Schroeder and Tipton (1968) noted that concentration of lead in the aorta increased with age and presumably with atherosclerosis in persons living in the United States. This communication presents the lead content of the aortas of eighteen male residents of Baltimore, Maryland. The data tend to support the earlier observations of Schroeder and Tipton (1968). (auth)

Placental Permeability of Lead

The detection of lead in fetal tissues by chemical analysis has long been accepted as prima facie evidence for the permeability of the placenta to this nonessential trace metal. However, only a few investigations, all on lower mammalian species, have contributed any direct experimental data bearing on this physiological process. Recent radioactive tracer and radioautographic studies on rodents have shown that lead crosses the placental membranes rapidly and in significant amounts even at relatively low maternal blood levels. While it is not possible to extrapolate directly the results of these experiments to humans because of differences in placental structure and other factors, the results do serve as a warning of the possible hazard to the human embryo and fetus of even low levels of lead in the maternal system.

Placental permeability of lead.

The detection of lead in fetal tissues by chemical analysis has long been accepted as prima facie evidence for the permeability of the placenta to this nonessential trace metal. However, only a few investigations, all on lower mammalian species, have contributed any direct experimental data bearing on this physiological process. Recent radioactive tracer and radioautographic studies on rodents have shown that lead crosses the placental membranes rapidly and in significant amounts even at relatively low maternal blood levels. While it is not possible to extrapolate directly the results of these experiments to humans because of differences in placental structure and other factors, the results do serve as a warning of the possible hazard to the human embryo and fetus of even low levels of lead in the maternal system.