Iron and copper accumulation in the brain of coxsackievirus-infected mice exposed to cadmium.

Cadmium (Cd) is a potentially toxic metal widely distributed in the environment and known to cause adverse health effects in humans. During coxsackievirus infection, the concentrations of essential and nonessential trace elements (e.g., iron (Fe), copper (Cu), and Cd) change in different target organs of the infection. Fe and Cu are recognized cofactors in host defence reactions, and Fe is known to be associated with certain pathological conditions of the brain. However, whether nonessential trace elements could influence the balance of essential trace elements in the brain is unknown. In this study the brain Fe, Cu, and Cd contents were measured through inductively coupled plasma mass spectrometry and their distributions determined by nuclear microscopy in the early phase (day 3) of coxsackievirus B3 (CB3) infection in nonexposed and in Cd-exposed female Balb/c mice. In CB3 infection the brain is a well-known target that has not been studied with regard to trace element balance. The brain concentration of Cu compared with that of noninfected control mice was increased by 9% (P < 0.05) in infected mice not exposed to Cd and by 10% (not significant) in infected Cd-exposed mice. A similar response was seen for Fe, which in infected Cd-exposed mice, compared to noninfected control mice, tended to increase by 16%. Cu showed an even tissue distribution, whereas Fe was distributed in focal deposits. Changes in Cd concentration in the brain of infected mice were less consistent but evenly distributed. Further studies are needed to define whether the accumulation and distribution of trace elements in the brain have an impact on brain function.

Influence of selenium on mercuric chloride cellular uptake and toxicity indicating protection: studies on cultured K-562 cells.

Selenium and mercuric chloride (MC) interactions regarding cellular uptake and selenium protection on MC toxicity have been studied. Human K-562 cells were pretreated or simultaneously treated with either selenite (5 or 50 microM) or selenomethionine (10 or 50 microM) together with MC (35 or 50 microM). Both treatments with selenite showed an increase of mercury uptake with increased selenium dose. In the pretreated or simultaneously treated selenite and 35 microM MC combinations, no inhibition of growth was seen, whereas all 50-microM MC combinations were toxic to the cells. A selenite-dependent protection was obtained for both exposure protocols when considering the cellular uptake of mercury. The cells died when the accumulation on d 4 reached more than about 0.8 x 10(-15) mol/cell of mercury, whereas they survived up to twofold more mercury uptake when exposed to selenite. Selenomethionine gave, with a few exceptions, similar effects as selenite on MC uptake and toxicity.

Selenite or selenomethionine interaction with methylmercury on uptake and toxicity showing a weak selenite protection: studies on cultured K-562 cells.

Selenium and methylmercuric chloride (MMC) interactions regarding cellular uptake and selenium protection on MMC toxicity have been studied. Human K-562 cells were pretreated or simultaneously treated with either selenite (5 or 50 microM) or selenomethionine (10 or 50 microM) together with (3.5 or 5 microM) MMC. Cells simultaneously treated with selenite or selenomethionine and 3.5 microM MMC showed a decreased mercury concentration with increased selenium dose especially seen in the selenite combinations. The simultaneous selenite and MMC 3.5 microM combinations showed growth curves with an increasing number of viable cells with increased selenite dose. All combinations with 5 microM MMC were toxic to the cells. Interactions between selenite or selenomethionine and MMC regarding cellular uptake of mercury and selenium were observed and indications of selenite protection against MMC toxicity in human K-562 cells were noticed.

Metal exposure from amalgam alters the distribution of trace elements in blood cells and plasma.

Twenty-seven consecutive patients with health problems associated with dental amalgam were recruited. In spite of thorough medical examinations, there were no diagnoses available. The patient group was dominated by women. A healthy age- and sex-matched control group with dental amalgams without symptoms was also recruited. Metal level monitoring in plasma and nuclear microscopy of isolated individual blood cells were carried out. Significant increases of copper, iron, zinc and strontium were found in patient plasma. There was no significant difference in plasma selenium between the groups. Mercury was significantly increased in patient plasma, although there was overlap between the groups. In erythrocytes a significant increase in calcium and a significant decrease in magnesium, copper, manganese and zinc were found. Calcium, magnesium, manganese and copper increased in patient neutrophil granulocytes. A significant decrease was found for zinc. A conspicuous finding was the presence of measurable mercury in a few of the cells from the patient but not in the control group. Thus, nuclear microscopy of isolated individual blood cells might provide a better diagnostic tool for metal exposure than blood plasma measurements.

Xenobiotic acceleration of idiopathic systemic autoimmunity in lupus-prone bxsb mice.

The diverse genetic backgrounds of lupus-prone murine models, which produce both quantitative and qualitative differences in disease expression, may be a valuable resource for studying the influence of environmental exposure on autoimmune disease in sensitive populations. We tested this premise by exposing autoimmune-prone BXSB and the nonautoimmune C57BL/6 mice to the heavy metal mercury. Although both strains express a nonsusceptible H-2 haplotype, exposure to mercury accelerated systemic autoimmunity in both male and female BXSB mice, whereas the C57BL/6 mice were resistant. The subclasses of antichromatin antibodies elicited in BXSB mice by mercury exposure were more consistent with the predominant Th1-type response of idiopathic disease than with the Th2-type response found in mercury-induced autoimmunity (HgIA). The appearance and magnitude of both humoral and cellular features of systemic autoimmunity correlated with the mercury dose. Furthermore, environmentally relevant tissue levels of mercury were associated with exacerbated systemic autoimmunity. These studies demonstrate that xenobiotic exposure can accelerate spontaneous systemic autoimmunity, and they support the possibility that low-level xenobiotic exposure enhances susceptibility to systemic autoimmunity in genetically susceptible individuals.

Uptake and retention of selenite and selenomethionine in cultured K-562 cells.

The selenium uptake and retention have been studied in K-562 cells exposed to selenite or selenomethionine. In the uptake experiments the cells were exposed to two doses of selenite (5 or 50 microM) or selenomethionine (10 or 50 microM). In the retention study the cells were treated for 2 h with the above mentioned doses of the selenocompounds before being observed at different times. The selenium uptake in cells exposed to selenite 5 microM began to saturate at 8 h, but increased again between 48 and 96 h. In cells exposed to selenite 50 microM the selenium uptake never reached a maximum, however, at 48 and 96 h the cell viability decreased strongly. The two doses of selenite showed different retention patterns, with a relatively small cellular decrease of selenium after treatment with selenite 5 microM compared to treatment with 50 microM of selenite. The selenium uptake in cells exposed to selenomethionine 10 microM or selenomethionine 50 microM began to saturate at 24 h and 48 h, respectively. The retention patterns were similar for both selenomethionine doses with a continuous decrease of the selenium concentration during the whole observation period. The results indicated a more controlled uptake and retention pattern of selenomethionine compared to selenite.

Trace element changes in the myocardium during coxsackievirus B3 myocarditis in the mouse.

During most infections plasma, concentrations of trace elements change, but it is unclear if this reflects changes in infected target tissues. In coxsackievirus B3 (CB3) infection, the myocardium is a target in both humans and mice. The concentrations of 12 trace elements were analyzed by inductively coupled plasma-mass spectrometry (ICP-MS) in the myocardium of sham-inoculated controls and infected A/J mice 4 and 7 d postinoculation. The size of the inflammatory lesion was positively correlated to the virus content of the heart, as estimated by histopathology and in situ hybridization, respectively. Iron, cobalt, vanadium, and selenium showed transient changes, whereas for the other elements, tendencies on d 4 were manifest on d 7. A three-fold increase in calcium on d 7 suggests prestages of calcification, whereas increases in zinc, selenium, and copper may be the result of the accumulation of immune cells. The magnesium decrease may contribute to the increased sensitivity to cardiac arrhythmias in myocarditis.

Effects of EDTA on trace elements and cardiovascular function in the anesthetised rabbit.

The present study was undertaken in order to study the effects of the broad-acting chelating agent CaNa2-EDTA on plasma trace elements and cardiovascular function in anesthetised New Zealand White rabbits. Trace elements are important for cardiovascular and immune functions and the rabbit is a well-accepted species in cardiovascular studies. The test compound CaNa2-EDTA was administered intravenously to rabbits at single doses of 4, 20, and 100 mg/kg. In addition, at 20 mg/kg, the effects of a second dose after 3 h were also investigated. Heart rate, blood pressure and body temperature were continuously monitored during a 6-h interval after injection of CaNa2-EDTA. Immediately before administration (-1 min) and at 3 and 6 h over the period of the experiment, the plasma cytokine response (tumor necrosis factor-alpha) and trace elements (Mn, Cu, Zn, Se, Ag, Cd, Hg, Pb) were measured. Regardless of dose, blood pressure was found to decrease, but no corresponding changes in heart rate were observed. Both a repeated administration of 20 mg/kg and a single dose of 100 mg/kg were detrimental and caused severe cardiovascular effects and lethality. alpha-TNF tended to increase, though only at 100 mg/kg. The electrocardiogram and body temperature were not affected by the treatment. The most pronounced trace element change was a dose-dependent increase in Mn that was equally pronounced at all time-points after the dose. There was an initial decrease in Cd at low dose levels (4 and 20 mg/kg) that turned into an increase after 6 h at 20 mg/kg and from 2 h at 100 mg/kg. A similar pattern with pronounced decreases at low dose levels was observed for Zn. Cu decreased similarly at all dose levels. For the other trace elements, no or inconsistent effects were observed. This model allows the study of concomitant cardiovascular and trace element changes during treatment with drugs and chelating agents preceding a possible lethal end point and associated pathophysiologic changes.

Differences in the growth inhibition of cultured K-562 cells by selenium, mercury or cadmium in two tissue culture media (RPMI-1640, Ham's F-10).

Effects of some metals on the growth of cultured human erythroleukemia K-562 cells were investigated when grown in two different types of media based upon RPMI-1640 or Ham's F-10. The study on proliferation, using RPMI-1640 supplemented with sodium selenite, selenomethionine, mercuric chloride, methylmercuric chloride and cadmium nitrate showed no inhibition of growth at concentrations of 2.5, 25, 25, 2.5 and 25 microM, while at 75, 250, 50, 5 and 50 microM toxicity was apparent. Selenite at 5-50 microM and selenomethionine at 50-100 microM inhibited the growth. In Ham's F-10 supplemented with the same compounds no inhibition was found at concentrations of 5, 10, 25, 1 and 50 microM, while at 50, 100, 50, 5 and 75 microM toxic effects were noted. Selenite 10 microM and selenomethionine 25-50 microM inhibited the proliferation. Measurements of trace element levels in pellets of K-562 cells grown in RPMI-1640 or Ham's F-10 unveiled higher cell contents of cadmium and selenium in cells grown in RPMI-1640, being consistent with higher concentrations of these elements in that medium. Manganese and mercury concentrations were higher in cells grown in Ham's F-10 correlating with a higher medium concentration of these elements. The growth responses and cellular uptake differed between the metals and the selenocompounds and although extrapolating the results to humans is difficult the selenium exposures were in approximately the same order of magnitude as in human exposures. The compounds could be ranked according to decreasing toxicity as: methylmercuric chloride > mercuric chloride, cadmium nitrate, sodium selenite > selenomethionine.

Measurement accuracy of aluminium content in bone.

The aluminium content in bone has been related in several ways: to the weight of wet bone, to the weight of dry bone, to the weight of bone-ash and to the calcium content of bone. We determined the accuracy and precision of measurement (using an inductively coupled mass-spectrometer) in 30 bone samples taken from one patient. The coefficient of variation of the aluminium/weight-quotient was 12.4 per cent for wet bone, 4.7 for dry bone and 5.0 for bone ash; and the coefficient of variation of the aluminium/calcium-weight-quotient was 7.5 per cent. Thus, the aluminium content in bone seems to be best related to the weight of dry bone.

Relation between trace element levels in plasma and myocardium during coxsackievirus B3 myocarditis in the mouse.

During most infections the plasma levels of trace elements change, but it is not clear if this reflects changes in the infected tissues. Coxsackievirus B3 (CB3) infection may result in viral replication, subsequent inflammation and changed trace element levels in the myocardium. In the present study, the trace element levels in the plasma and heart of adult male A/J mice were determined during the pre-inflammatory stage (day 4) of CB3 myocarditis for the following trace elements: aluminium (Al), arsenic (As), calcium (Ca), cobalt (Co), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), selenium (Se), silver (Ag), vanadium (V) and zinc (Zn). The severity of the infection was assessed through clinical signs of disease and trace element levels were measured through inductively-coupled plasma mass-spectrometry (ICP-MS). In the heart, the levels decreased for V (59%; p < 0.01), Co (38%; p < 0.01), Al (81%; p < 0.01), As (66%; p < 0.01) and Se (16%; p < 0.01). Increased levels were detected for Mn (13%; p < 0.05), Fe (48%; p < 0.01), Cu (34%; p < 0.01) and Ag (46%; p < 0.01). In the plasma, decreases were detected in the level of Zn (32%; p < 0.05), whereas increases were seen in Mn (362%; p < 0.05), Fe (272%; p < 0.01), Co (71%; p < 0.05), Cu (25%; n.s.) and Mg (43%; p < 0.01) levels. A correlation was found between the levels in plasma and myocardium for Co (r(s) = -0.636; p < 0.05), Fe (r(s) = 0.764; p < 0.05), Mn (r(s) = 0.682; p < 0.05) and Mg (r(s) = -0.791; p < 0.05). Thus, determination of some of these trace elements in the plasma may be useful to indicate target tissue involvement in the early pre- inflammatory stage of an infectious disease. Some of these elements are important nutrients for the immune system, while others may be associated with the development of disease complications, such as cardiac arrhythmias.

Trace element distribution in heart tissue sections studied by nuclear microscopy is changed in Coxsackie virus B3 myocarditis in methyl mercury-exposed mice.

Methyl mercury (MeHg) has been shown to change Coxsackie virus type B3 (CB3) myocarditis in a direction compatible with the development of chronic disease. Murine models of CB3 myocarditis closely mimic the pathogenesis in humans. There are also indications that metals, such as mercury, and trace elements may interact and adversely affect viral replication and development of inflammatory lesions. The effects of low-dose MeHg exposure on myocardial trace element distribution, as determined by means of nuclear microscopy, was studied in CB3 myocarditis. Balb/c mice were fed a MeHg-containing diet (3.9 mg/kg diet) for 12 wk prior to infection. Areas of inflammatory lesions in the myocardium were identified by traditional histologic examination, and serial tissue sections in these selected areas were used for immune histology (macrophages), in situ hybridization of virus genomes, and nuclear microscopy of tissue trace element distribution. Areas with no inflammation or virus were compared with areas of ongoing inflammation and viral replication. In the inflammatory lesions of MeHg-exposed mice as compared to nonexposed mice, the myocardial contents of calcium (Ca), manganese (Mn), and iron (Fe) were significantly increased, whereas the zinc (Zn) content was decreased. The increased Ca and decreased Zn contents in the inflamed heart may partly explain a more severe disease in MeHg-exposed individuals. Although not significant in the present study, with a limited number of mice, the inflammatory and necrotic lesions in the ventricular myocardium on d 7 of the infection was increased by 50% (from 2.2% to 3.3% of the tissue section area) in MeHg-exposed mice and, also, there was a tendency of increased persistence of virus with MeHg exposure. No increased MeHg uptake, either in the inflammatory lesions or in the areas of noninflamed heart tissue in infected mice, could be detected. The present results indicate that a "competition" exists between potentially toxic heavy metals from the environment/diet and important trace elements in the body and that a disturbed trace element balance adversely influences the development of pathophysiologic changes in inflammatory heart disease.

Activation of the immune system and systemic immune-complex deposits in Brown Norway rats with dental amalgam restorations.

Dental amalgam restorations are a significant source of mercury exposure in the human population, but their potential to cause systemic health effects is highly disputed. We examined effects on the immune system by giving genetically mercury-susceptible Brown Norway (BN) rats and mercury-resistant Lewis (LE) rats silver amalgam restorations in 4 molars of the upper jaw, causing a body burden similar to that described in human amalgam-bearers (from 250 to 375 mg amalgam/kg body weight). BN rats with amalgam restorations, compared with control rats given composite resinous restorations, developed a rapid activation of the immune system, with a maximum 12-fold increase of the plasma IgE concentration after 3 wks (p < 0.001; Mann-Whitney's test). LE rats receiving amalgam restorations showed no significant increase of plasma IgE (p > 0.05). After 12 wks, BN rats with amalgam restorations showed significantly increased (p < 0.05) titers of immune-complex (IC) deposits in the renal glomeruli and in the vessel walls of internal organs. These rats also showed a significant (p < 0.05), from six- to 130-fold, increase in tissue mercury concentration in the concentration order kidney > spleen > cerebrum occipital lobe > cerebellum > liver > thymus, and the tissue silver concentration was significantly (p < 0.05) increased from three- to 11-fold. Amalgam-implanted BN rats showed a significant (p < 0.05) increase in copper concentration in the kidney and spleen, and in kidney selenium concentration. We conclude that dental amalgam restorations release substantial amounts of their elements, which accumulate in the organs and which, in genetically susceptible rats, give rise to activation of the immune system and systemic IC deposits.

Effects of Pb2+, Ni2+, Hg2+ and Se4+ on cultured cells. Analysis of uptake, toxicity and influence on radiosensitivity.

Effects of Pb2+, Ni2+, Hg2+ and Se4+ on cultured human glioma U-343MG cells were investigated considering uptake, toxicity and, in combination with radiation, clonogenic cells survival. The cells were exposed to 0-100 microM of the metals for a week before the evaluation. The tests showed a tendency to toxicity with 10 microM nickel although not significant (P > 0.05). Selenium, lead and mercury exerted a significant toxicity (P < 0.05) at 2.5 microM, 10 microM and 1 microM, respectively. To challenge the clonogenic cell survival capacity, the cells were irradiated with 60Co photons after being exposed to the highest nontoxic concentration of the different metals. The clonogenic cell survival tests, after irradiation, showed no significant change if the cells were exposed to 5 microM nickel, 0.5 microM selenium or 5 microM lead compared with those not exposed. Mercury, 0.1 microM, gave a relative reduction in survival compared with only irradiated cells of 58 +/- 17%. Thus, only mercury affected the radiation-induced damage and/or repair. When exposed to the highest nontoxic concentrations of the different metals, the cultures did not display a significant uptake ratio (metal concentration ratio of exposed cells to control cells) of nickel (3.1 +/- 3.3), only a small uptake ratio of selenium (4.0 +/- 0.4), while there was a large uptake ratio of both lead (2.6 +/- 1.7) x 10(2) and mercury (1.5 +/- 0.2) x 10(1). The results indicated that nickel was neither especially toxic nor influenced the clonogenic cell survival after irradiation. Mercury was more toxic and also influenced the radiation sensitivity. Lead was taken up strongly but did not influence the radiation sensitivity. Selenium accumulated but gave no detectable effect on the radiation sensitivity.

Effects of administration of antioxidants in acute intermittent porphyria.

In order to elucidate the question of free radical involvement in acute porphyric crisis, antioxidants were administered to two acute intermittent porphyria patients with long-standing recurrent attacks. Clinical condition and urinary excretion of porphyrins and porphyrin precursors were monitored before, during and after an eight week therapy with daily doses of vitamin E, beta-carotene, ascorbic acid, selenium, vitamin Q, acetylcysteine, mannitol and carnitine. Blood cell trace element profiles were followed. The administration of the compound antioxidant formula was found not to further impair the clinical or biochemical conditions of the patients but the incidence of the recurrent crises or the severity of the symptoms were not positively affected. Aberrant blood cell trace element profiles with increased granulocyte manganese were normalized during treatment, on cessation of the therapy again resuming the abnormal pretreatment patterns, which may suggest an origin in oxidative stress. No correlation was observed between the concentration of granulocyte manganese and the excretion of 5-aminolaevulinic acid. Indications for participation of this porphyrin precursor in a radical generating process leading to generalized mitochondrial superoxide dismutase induction, as conceivably signalled by increased intracellular manganese, were thus not obtained. The failure to note a clinical response to antioxidant therapy may be due to factors dependent upon dosage of, or interaction between, the antioxidant compounds given, or on restricted bioavailability of the antioxidants at critical anatomical sites, and does not per se invalidate the model of acute porphyria as a hyperoxidative condition.

Pathogenic mechanisms of the acute porphyric attack: speculative roles of manganese associated enzymes.

The significantly increased concentrations of granulocyte manganese in subjects with AIP may be an indication of overexpression of manganese-associated enzymes. In this study we present further observations related to this phenomenon and speculate that this may provide a rational basis for hypotheses attempting to explain the pathogenesis of the acute attack of porphyria. Such hypotheses are advanced with regard to pyruvate carboxylase, mitochondrial superoxide dismutase and glutamine synthetase, three manganese-dependent enzymes associated with either ALA-generating or ALA-dependent processes. The metabolic impacts in acute porphyria of these enzymes would be functions of the current energy charge of the organism, and would thus explain the protecting and ameliorating effects of glucose in these conditions. Although granulocytes from AIP subjects have elevated manganese concentrations, this did not appear to be associated with increased activities of two enzymes assayed, pyruvate carboxylase or mitochondrial superoxide dismutase. However, enzyme activities in white blood cells do not necessarily represent the levels of catalytic activity in cell types involved in the phenotypic expression of porphyria. Thus it proposed that hypotheses along these new lines of thinking are not flawed by the apparently missing correlations, and should not be therefore discarded. The possible roles of manganese-associated enzymes in the mechanisms behind the acute porphyric attack are discussed in some detail in the paper.

Aluminum, Alzheimer's disease and bone fragility.

The incidence of fragility fractures has increased epidemically. Especially patients with senile dementia (including Alzheimer's disease) have a greatly increased risk of fragility fractures. Aluminum inhibits bone mineralization; the greater the aluminium exposure, the higher the risk of an early fracture. Aluminium is neurotoxic and may, in addition to genetic factors, play a role in the development of Alzheimer's disease by contributing to the formation of the characteristic beta-amyloid and neurofibrillary tangles. Thus, a common denominator between Alzheimer's disease and bone fragility may be a chronic low-grade aluminum intoxication. The epidemic of fragility fractures may be caused by increased aluminium exposure--due to the use of aluminum cooking pots or the pollution acidification of our environment. In our pilot study of 26 hip-fracture patients (13 patients with Alzheimer's disease and 13 individually age- and gender-matched non-demented patients), the aluminum content, determined mass-spectro-metrically, was higher in trabecular bone biopsies from the patients with Alzheimer's disease than from the non-demented patients (p = 0.005). The aluminum content was also higher in the younger of the 26 patients (p = 0.02). Our findings agree with the hypothesis that aluminum plays a role in the development of Alzheimer's disease and bone fragility.

Murine genotype influences the specificity, magnitude and persistence of murine mercury-induced autoimmunity.

Genetic factors are major contributors in determining the susceptibility to systemic autoimmune diseases. We studied the influence of genotype on systemic autoimmunity by treating female mice of the H-2s strains SJL/N, SJL/J, A.SW, and B10.S with mercuric chloride (HgCl2) for 10 weeks and then following autoantibody and tissue immune deposits during the subsequent 12 months. All strains developed antinucleolar antibodies (ANoA) of the IgG class which reacted in immunoblotting with a 34-kDa nucleolar protein identified as fibrillarin. The titre of ANoA attained after 10 weeks' treatment varied from 1:1,280 to 1:20,480 in the order: A.SW > SJL > > B10.S. Following cessation of HgCl2 treatment ANoA and antifibrillarin antibodies (AFA) persisted for up to 12 months, although some B10.S mice showed pronounced reduction not only of their autoantibody titres, but also systemic immune deposits when compared to other H-2s strains. A second set of autoantibodies targeted chromatin and in some mice specifically histones, and were distinguished from the ANoA by a rapid decline after treatment and a susceptibility linked to the non-H-2 genes of the SJL. Tissue levels of mercury remained elevated above untreated controls throughout the study period, suggesting that the mercury detected in lymphoid tissues may provide stimulation of lymphoid cells specific for fibrillarin for a considerable period after exposure has ceased. We conclude that H-2 as well as non-H-2 genetic factors distinctly influence not only the susceptibility to induction of autoimmunity, but also the specificity and magnitude of the response.

Selenium protection against toxicity from cadmium and mercury studied at the cellular level.

Interaction between selenium and the heavy metals cadmium and mercury was studied in an experimental rat model (Sprague-Dawley). The rats were administered either one single trace element or combinations of selenium and cadmium as well as selenium and mercury. Salts of these trace elements were administered intraperitoneally daily during thirty days. Thereafter the animals were sacrificed and kidneys and livers excised rapidly. Thin sections were produced by a cryotome and subsequently freeze-dried. Nuclear microscopy of the sections showed that in the combination groups there was a co-localization of selenium and the heavy metals. None of the expected pathological signs of cadmium and mercury toxicity were observed. The conclusion was that selenium exerted a protective effect against the toxicity of cadmium and mercury through mechanisms still to be unveiled.

New aspects of murine coxsackie B3 myocarditis--focus on heavy metals.

The magnitude of inflammatory lesions in the hearts of coxsackie B3 (CB3)-virus infected mice can be affected by the potentially toxic heavy metals cadmium (Cd), nickel (Ni) and methyl mercury (MeHg). The infection is associated with a changed distribution, such as Cd accumulation in the spleen and kidneys. New target organs for Ni during the infection were the heart, pancreas and lungs in which inflammatory lesions were present. This increased uptake was correlated with the disturbed function of immune cells and an increased inflammatory reaction. Ni and MeHg appeared to have a direct effect on immune cells that resulted in changed natural killer cell activity and decreased mobilization of macrophages, CD4+ and CD8+ cells into the inflammatory lesions. Although MeHg increased spleen T cell activity and gamma-interferon (IFN-gamma) levels, the inflammatory lesions in the heart increased. Another detrimental effect of MeHg treatment was evident by an increased calcium and decreased zinc content in the inflamed heart, which may partly explain the more severe inflammatory lesion. The host's response, CB3 infection, changed the distribution of each metal in a specific way, a fact which may subsequently result in altered target organ toxicity and resistance to the infection.