Blood and brain mercury levels after chronic gestational exposure to methylmercury in rats.
(17/1685)
Female rats were exposed to 0, 0.5, or 6 ppm Hg (as methylmercuric chloride, 10 rats/group) in drinking water. For half the rats, exposure began 4 weeks before mating and for the others, exposure began 7 weeks before mating. All mating was done with an unexposed male. Maternal exposure continued to post-natal day (PN) 16. Blood and whole-brain mercury concentrations were determined in pups on PN 0 (birth) and PN 21 (weaning). Maternal water consumption was monitored daily during gestation and lactation. Maternal water consumption increased 2- to 3-fold through gestation for all groups. Mercury levels in blood and brain were unrelated to the duration of exposure before mating, although reproductive success appeared to be so related. Mercury levels in both media were closely related to consumption during gestation, but apparently maternal exposure during lactation did not result in exposure to the nursing pups. Brain mercury in offspring decreased between birth and weaning from 0.49 to 0.045 ppm in the low-dose rats and from 9.8 to 0.53 ppm in the high-dose rats. The brain increased in weight only about 5.5-fold during this time, indicating that there was minimal mercury exposure and some net loss from brain during this period. Brain:blood ratios averaged about 0.14 at birth and 0.24 at weaning, suggesting differential loss from neural and non-neural tissue. These ratios are higher than those reported in studies using less chronic exposure conditions or with adult rats. Brain concentrations of mercury in females in the low-dose group were about 10-15% higher than those seen in their male siblings. At the higher dose, the males had slightly higher levels of mercury in the brain than did their female siblings at birth. The relationship between brain concentration (in ppm) and cumulative mercury consumption, also expressed on a ppm basis (cumulative mercury consumed divided by maternal body weight at parturition), was not linear but was well described by a power-function relationship: Hg = A*(cum exposure)b where the exponent, b, was 1.12 and 1.17 for blood and brain, respectively, at birth. This exponent was indistinguishable from 1.0 for both media at weaning, indicating that the relationship between exposure and blood and brain levels became linear. (+info)
Effects of mercury on the arterial blood pressure of anesthetized rats.
(18/1685)
The available data suggests that hypotension caused by Hg2+ administration may be produced by a reduction of cardiac contractility or by cholinergic mechanisms. The hemodynamic effects of an intravenous injection of HgCl2 (5 mg/kg) were studied in anesthetized rats (N = 12) by monitoring left and right ventricular (LV and RV) systolic and diastolic pressures for 120 min. After HgCl2 administration the LV systolic pressure decreased only after 40 min (99 +/- 3.3 to 85 +/- 8.8 mmHg at 80 min). However, RV systolic pressure increased, initially slowly but faster after 30 min (25 +/- 1.8 to 42 +/- 1.6 mmHg at 80 min). Both right and left diastolic pressures increased after HgCl2 treatment, suggesting the development of diastolic ventricular dysfunction. Since HgCl2 could be increasing pulmonary vascular resistance, isolated lungs (N = 10) were perfused for 80 min with Krebs solution (continuous flow of 10 ml/min) containing or not 5 microM HgCl2. A continuous increase in pulmonary vascular resistance was observed, suggesting the direct effect of Hg2+ on the pulmonary vessels (12 +/- 0.4 to 29 +/- 3.2 mmHg at 30 min). To examine the interactions of Hg2+ and changes in cholinergic activity we analyzed the effects of acetylcholine (Ach) on mean arterial blood pressure (ABP) in anesthetized rats (N = 9) before and after Hg2+ treatment (5 mg/kg). Using the same amount and route used to study the hemodynamic effects we also examined the effects of Hg2+ administration on heart and plasma cholinesterase activity (N = 10). The in vivo hypotensive response to Ach (0.035 to 10.5 microg) was reduced after Hg2+ treatment. Cholinesterase activity (microM h-1 mg protein-1) increased in heart and plasma (32 and 65%, respectively) after Hg2+ treatment. In conclusion, the reduction in ABP produced by Hg2+ is not dependent on a putative increase in cholinergic activity. HgCl2 mainly affects cardiac function. The increased pulmonary vascular resistance and cardiac failure due to diastolic dysfunction of both ventricles are factors that might contribute to the reduction of cardiac output and the fall in arterial pressure. (+info)
Eliminating mercury use in hospital laboratories: a step toward zero discharge.
(19/1685)
In 1996, the Western Lake Superior Sanitary District initiated a Zero Discharge Project to work toward the goal of zero discharge of persistent toxic substances from its wastewater treatment plant. This multifaceted project focuses on mercury, lead, dioxin, polychlorinated biphenyls, and hexachlorbenzene. Here, the author describes a collaboration with local hospitals to eliminate the use of mercury-containing fixatives by histopathology laboratories. Three primary roadblocks to change were identified: (a) technicians' belief that pathologists would be resistant to change; (b) lack of time to research alternatives; (c) lack of awareness of the hospital's role in polluting the environment. (+info)
Metals and kidney autoimmunity.
(20/1685)
The causes of autoimmune responses leading to human kidney pathology remain unknown. However, environmental agents such as microorganisms and/or xenobiotics are good candidates for that role. Metals, either present in the environment or administered for therapeutic reasons, are prototypical xenobiotics that cause decreases or enhancements of immune responses. In particular, exposure to gold and mercury may result in autoimmune responses to various self-antigens as well as autoimmune disease of the kidney and other tissues. Gold compounds, currently used in the treatment of patients with progressive polyarticular rheumatoid arthritis, can cause a nephrotic syndrome. Similarly, an immune-mediated membranous nephropathy frequently occurred when drugs containing mercury were commonly used. Recent epidemiologic studies have shown that occupational exposure to mercury does not usually result in autoimmunity. However, mercury induces antinuclear antibodies, sclerodermalike disease, lichen planus, or membranous nephropathy in some individuals. Laboratory investigations have confirmed that the administration of gold or mercury to experimental animals leads to autoimmune disease quite similar to that observed in human subjects exposed to these metals. In addition, studies of inbred mice and rats have revealed that a few strains are susceptible to the autoimmune effects of gold and mercury, whereas the majority of inbred strains are resistant. These findings have emphasized the importance of genetic (immunogenetic and pharmacogenetic) factors in the induction of metal-associated autoimmunity. (italic)In vitro(/italic) and (italic)in vivo(/italic) research of autoimmune disease caused by mercury and gold has already yielded valuable information and answered a number of important questions. At the same time it has raised new issues about possible immunostimulatory or immunosuppressive mechanisms of xenobiotic activity. Thus it is evident that investigations of metal-induced renal autoimmunity have the potential to produce new knowledge with relevance to autoimmune disease caused by xenobiotics in general as well as to idiopathic autoimmunity. (+info)
Exposure to polychlorinated biphenyls and levels of thyroid hormones in children.
(21/1685)
As part of an epidemiologic study on exposure to a toxic waste incineration plant we investigated whether blood concentrations of polychlorinated biphenyls (PCBs), lead, and cadmium, as well as concentration of mercury in 24-hr urine samples were associated with thyroid hormone status. As an indication of status, we determined levels of thyroid-stimulating hormone (TSH), free thyroxine (FT(4)), and free triiodothyronine (FT(3)) in children living in households where [less than/equal to] 10 cigarettes were smoked per day. Eight PCB congeners (PCBs 101, 118, 138, 153, 170, 180, 183, and 187) were measured in whole blood samples. Of these, seven congeners (PCB 101 was not detected in any sample) and the sum of all PCB congeners were analyzed as predictors for thyroid hormone status in separate linear regression models adjusted for potential confounders. In addition, the possible effects of cadmium, lead, and mercury on levels of thyroid hormones were examined. Blood concentrations and information on questionnaire data were available for 320 children 7-10 years of age. We found a statistically significant positive association between the mono-ortho congener PCB 118 and TSH as well as statistically significant negative relationships of PCBs 138, 153, 180, 183, and 187 to FT(3). There was no association for the PCB congeners and FT(4). Blood cadmium concentration was associated with increasing TSH and diminishing FT(4). Blood lead and urine concentration of mercury were of no importance to thyroid hormone levels. The results stress the need for future studies on the possible influences of PCB and cadmium exposure on thyroid hormones, particularly in children. These studies should also take neurologic development into account. (+info)
Neuropsychological effects associated with exposure to mercury vapor among former chloralkali workers.
(22/1685)
OBJECTIVES: This investigation studied possible neuropsychological effects among former chloralkali workers with past exposure to mercury vapor. METHODS: Seventy-five formerly exposed workers who had been examined with an extensive neuropsychological test battery were compared with 52 referents frequency-matched for age. The tests measured general cognitive function, motor and psychomotor function, attention, memory, and learning. The groups were similar in educational level, age, and verbal comprehension. The mean exposure time to mercury vapor in the index group was 7.9 (range 1.1-36.2) years with an annual mean urinary mercury concentration of 539 (range 41-2921) nmol/(l x year). The mean time since the cessation of exposure was 12.7 (range 1.0-35.0) years. RESULTS: Performance on the grooved pegboard (dominant hand 75.8 versus 70.9 seconds, P<0.05; nondominant hand 82.2 versus 76.3 seconds, P=0.02) and the Benton visual retention test (mean number of correct reproductions 6.9 versus 7.5, P<0.05) was poorer among the formerly exposed workers when compared with the referents. In addition the subjects who had experienced the highest intensity of exposure [cumulative urinary mercury index > or =550 nmol/(l x year)] had a poorer performance on the trailmaking test, part A and B, on the digit symbol test, and on the word pairs test (retention errors). CONCLUSIONS: The presented results suggest a slight persistent effect of mercury vapor exposure on the central nervous system, mainly involving motor functions and attention, but also possibly related to the visual system. Previous exposure does not seem to have affected the workers' general intellectual level or their ability to reason logically. (+info)
Inhibition of Na(+)-K(+)-2Cl(-) cotransport by mercury.
(23/1685)
Mercury alters the function of proteins by reacting with cysteinyl sulfhydryl (SH(-)) groups. The inorganic form (Hg(2+)) is toxic to epithelial tissues and interacts with various transport proteins including the Na(+) pump and Cl(-) channels. In this study, we determined whether the Na(+)-K(+)-Cl(-) cotransporter type 1 (NKCC1), a major ion pathway in secretory tissues, is also affected by mercurial substrates. To characterize the interaction, we measured the effect of Hg(2+) on ion transport by the secretory shark and human cotransporters expressed in HEK-293 cells. Our studies show that Hg(2+) inhibits Na(+)-K(+)-Cl(-) cotransport, with inhibitor constant (K(i)) values of 25 microM for the shark carrier (sNKCC1) and 43 microM for the human carrier. In further studies, we took advantage of species differences in Hg(2+) affinity to identify residues involved in the interaction. An analysis of human-shark chimeras and of an sNKCC1 mutant (Cys-697-->Leu) reveals that transmembrane domain 11 plays an essential role in Hg(2+) binding. We also show that modification of additional SH(-) groups by thiol-reacting compounds brings about inhibition and that the binding sites are not exposed on the extracellular face of the membrane. (+info)
Influence of exogenous thiols on inorganic mercury-induced injury in renal proximal and distal tubular cells from normal and uninephrectomized rats.
(24/1685)
Inorganic mercury (Hg(2+)) induced time- and concentration-dependent cellular injury in freshly isolated proximal tubular (PT) and distal tubular (DT) cells from normal (control) rats or uninephrectomized (NPX) rats. PT cells from NPX rats were more susceptible than PT cells from control rats, and DT cells were slightly more susceptible than PT cells to cellular injury induced by Hg(2+) (not bound to a thiol). Preloading cells with glutathione increased Hg(2+)-induced cellular injury in PT cells from control rats. However, coincubation of PT or DT cells from control or NPX rats with Hg(2+) and glutathione (1:4) provided significant protection relative to incubations with Hg(2+) alone. No support was obtained for a role for gamma-glutamyltransferase in glutathione-dependent protection. However, the organic anion carrier does appear to play a role in accumulation and toxicity of mercuric conjugates of cysteine in PT cells from control, but not NPX, rats. Coincubation with Hg(2+) and cysteine (1:4) had little effect on, or slightly enhanced, Hg(2+)-induced cellular injury at low concentrations of Hg(2+) in all cells studied. Coincubation with Hg(2+) and albumin (1:4) markedly protected PT and DT cells from control and NPX rats at all concentrations except the highest concentration of Hg(2+) in DT cells from NPX rats. 2,3-Dimercapto-1-propanesulfonic acid protected cells both when preloaded or added simultaneously with Hg(2+). Thus, renal cells from NPX rats are more susceptible to Hg(2+)-induced injury, PT and DT cells respond differently to exposure to Hg(2+), and thiols can significantly modulate the toxic response to Hg(2+). (+info)