The effects of selenium biofortification on mercury bioavailability and toxicity in the lettuce-slug food chain.

The effects of foliar Se biofortification (Se+) of the lettuce on the transfer and toxicity of Hg from soil contaminated with HgCl2 (H) and soil collected near the former Hg smelter in Idrija (I), to terrestrial food chain are explored, with Spanish slug as a primary consumer. Foliar application of Se significantly increased Se content in the lettuce, with no detected toxic effects. Mercury exerted toxic effects on plants, decreasing plant biomass, photochemical efficiency of the photosystem II (Fv/Fm) and the total chlorophyll content. Selenium biofortification (Se+ test group) had no effect on Hg bioaccumulation in plants. In slugs, different responses were observed in H and I groups; the I/Se+ subgroup was the most strongly affected by Hg toxicity, exhibiting lower biomass, feeding and growth rate and a higher hepatopancreas/ muscle Hg translocation, pointing to a higher Hg mobility in comparison to H group. Selenium increased Hg bioavailability for slugs, but with opposite physiological responses: alleviating stress in H/Se+ and inducing it in I/Se+ group, indicating different mechanisms of Hg-Se interactions in the food chain under HgCl2 and Idrija soil exposures that can be mainly attributed to different Hg speciation and ligand environment in the soil.

Bioavailability study of arsenic and mercury in traditional Chinese medicines (TCM) using an animal model after a single dose exposure.

Traditional Chinese medicines (TCM) are increasingly being used as alternative medicines in many countries, and this has caused concern because of adverse health effects from toxic metal bioavailability such as mercury (Hg) and arsenic (As). The aim of this study was to investigate the bioavailability of As and Hg from TCM after a single exposure dose using an animal model of female Sprague-Dawley rats. The rats were divided into 6 groups which included four groups treated with sodium arsenite (NaAsO2), arsenic sulfide (As2S3), mercuric chloride (HgCl2), mercuric sulfide (HgS), and two groups treated with TCM containing high Hg or As (Liu Shen Wan: As 7.7-9.1% and Hg 1.4-5.0%; Niuhang Jie du Pian: As 6.2-7.9% and Hg <0.001%). The samples of urine, faeces, kidney and liver were collected for analysis and histological assay. The results indicated that relatively low levels of As and Hg from these TCM were retained in liver and kidney tissues. The levels of As in these tissues after TCM treatment were consistent with the levels from the As sulphide treated group. With the exception of the mercuric chloride treated group, the levels of Hg in urine from other groups were very low, and high levels of As and Hg from TCM were excreted in faeces. The study showed poor bioavailability of As and Hg from TCM as indicated by low relative bioavailability of As (0.60-1.10%) and Hg (<0.001%). Histopathological examination of rat kidney and liver tissues did not show toxic effects from TCM.

Safety evaluation of mercury based Ayurvedic formulation (Sidh Makardhwaj) on brain cerebrum, liver & kidney in rats.

BACKGROUND & OBJECTIVES: Sidh Makardhwaj (SM) is a mercury based Ayurvedic formulation used in rheumatoid arthritis and neurological disorders. However, toxicity concerns due to mercury content are often raised. Therefore, the present study was carried out to evaluate the effect of SM on brain cerebrum, liver and kidney in rats. METHODS: Graded doses of SM (10, 50, 100 mg/kg), mercuric chloride (1 mg/kg) and normal saline were administered orally to male Wistar rats for 28 days. Behavioural parameters were assessed on days 1, 7, 14 and 28 using Morris water maze, passive avoidance, elevated plus maze and rota rod. Liver and kidney function tests were done on day 28. Animals were sacrificed and brain cerebrum acetylcholinesterase activity, levels of malondialdehyde (MDA), reduced glutathione (GSH) in brain cerebrum, liver, kidney were estimated. The levels of mercury in brain cerebrum, liver and kidney were estimated and histopathology of these tissues was also performed. RESULTS: SM in the doses used did not cause significant change in neurobehavioural parameters, brain cerebrum AChE activity, liver (ALT, AST, ALP bilirubin) and kidney (serum urea and creatinine) function tests as compared to control. The levels of mercury in brain cerebrum, liver, and kidney were found to be raised in dose dependent manner. However, the levels of MDA and GSH in these tissues did not show significant changes at doses of 10 and 50 mg/kg. Also, there was no histopathological change in cytoarchitecture of brain cerebrum, liver, and kidney tissues at doses of 10 and 50 mg/kg. INTERPRETATION & CONCLUSIONS: The findings of the present study suggest that Sidh Makardhwaj upto five times the equivalent human dose administered for 28 days did not show any toxicological effects on rat brain cerebrum, liver and kidney.

Full recovery from a potentially lethal dose of mercuric chloride.

INTRODUCTION: Mercuric chloride poisoning is rare yet potentially life-threatening. We report a case of poisoning with a potentially significant amount of mercuric chloride which responded to aggressive management. CASE REPORT: A 19-year-old female presented to the Emergency Department with nausea, abdominal discomfort, vomiting of blood-stained fluid, and diarrhea following suicidal ingestion of 2-4 g of mercuric chloride powder. An abdominal radiograph showed radio-opaque material within the gastric antrum and the patient's initial blood mercury concentration was 17.9 µmol/L (or 3.58 mg/L) at 3 h post-ingestion. Given the potential toxicity of inorganic mercury, the patient was admitted to the intensive care unit and chelation with dimercaprol was undertaken. Further clinical effects included mild hemodynamic instability, acidosis, hypokalemia, leukocytosis, and fever. The patient's symptoms began to improve 48 h after admission and resolved fully within a week. DISCUSSION: Mercuric chloride has an estimated human fatal dose of between 1 and 4 g. Despite a reported ingestion of a potentially lethal dose and a high blood concentration, this patient experienced mild to moderate poisoning only and she responded to early and appropriate intervention. Mercuric chloride can produce a range of toxic effects including corrosive injury, severe gastrointestinal disturbances, acute renal failure, circulatory collapse, and eventual death. Treatment includes close observation and aggressive supportive care along with chelation, preferably with 2,3-dimercapto-1-propane sulfonate or 2,3-meso-dimercaptosuccinic acid.

Nephrotoxicity of mercuric chloride, methylmercury and cinnabar-containing Zhu-Sha-An-Shen-Wan in rats.

Cinnabar (HgS) is used in traditional medicines, and total Hg content is used for risk assessment of cinnabar-containing traditional medicines such as Zhu-Sha-An-Shen-Wan (ZSASW). Is ZSASW or cinnabar toxicologically similar to common mercurials? Adult Sprague-Dawley rats were gavaged with ZSASW (1.4 g/kg), cinnabar (0.2g/kg), HgCl(2) (0.02 g/kg), MeHg (0.001 g/kg), or saline daily for 60 days, and toxicity was determined. Animal body-weight gain was decreased by HgCl(2) and MeHg. Blood urea nitrogen (BUN) was increased by MeHg. Histology showed severe kidney injury following MeHg and HgCl(2) treatments, but mild after ZSASW and cinnabar. Renal Hg contents were markedly increased in the HgCl(2) and MeHg groups but were not elevated in the ZSASW and cinnabar groups. The expression of kidney injury molecule-1 was increased 50-fold by MeHg, 4-fold by HgCl(2), but was unaltered by ZSASW and cinnabar; the expression of matrilysin was increased 3-fold by MeHg. In contrast, the expression of N-cadherin was decreased by HgCl(2). Thus, ZSASW and cinnabar are much less nephrotoxic than HgCl(2) and MeHg, indicating that chemical forms of mercury underlie their disposition and toxicity.

Realgar- and cinnabar-containing an-gong-niu-huang wan (AGNH) is much less acutely toxic than sodium arsenite and mercuric chloride.

An-gong-niu-huang wan (AGNH) is a famous traditional Chinese medicine used for brain trauma, hemorrhage, and coma. AGNH contains 10% realgar (As4S4) and 10% cinnabar (HgS). Both As and Hg are well-known for their toxic effects, and the safety of AGNH is of concern. To address this question, the acute toxicity of AGNH, realgar and cinnabar were compared to sodium arsenite (NaAsO2) and mercuric chloride (HgCl2). Mice were administrated orally AGNH at 1, 3 and 6g/kg. AGNH at 3g/kg contains 2.8mmol As/kg as realgar and 1.18mmol Hg/kg as cinnabar. Realgar, cinnabar, arsenite (0.28 mmol/kg, 10% of realgar) and HgCl2 (0.256 mmol/kg, 20% of cinnabar) were orally given to mice for comparison. Blood and tissues were collected 8h later for toxicity evaluation. Serum alanine aminotransferase was increased by arsenite and blood urea nitrogen was increased by HgCl2. Total As accumulation after arsenite in liver (100-fold) and kidney (13-fold) was much higher than that after realgar. The accumulation of Hg after HgCl2 in liver was 400-fold higher and kidney 30-fold higher than after cinnabar. Histopathology showed moderate liver and kidney injuries after arsenite and HgCl2, but injuries were mild or absent after AGNH, realgar, and cinnabar. The expression of metallothionein-1, a biomarker of metal exposure, was increased 4-10-fold by arsenite and HgCl2, but was unchanged by AGNH, realgar and cinnabar. Thus, AGNH, realgar and cinnabar are much less toxic acutely than arsenite and HgCl2. The chemical forms of As and Hg are extremely important factors in determining their disposition and toxicity.

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.

Influence of 2,3-dimercaptopropane-1-sulfonate (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) on the renal disposition of mercury in normal and uninephrectomized rats exposed to inorganic mercury.

The effects of the water-soluble chelating agents 2,3-dimercapto-1-propane sulfonate (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) on the renal disposition of inorganic mercury were studied in normal and uninephrectomized (NPX) rats injected (i.v.) with a nontoxic 0.5-mumol/kg dose of mercuric chloride (HgCl2). When a 100-mg/kg dose of either DMPS or DMSA was injected (i.p.) 24 and 30 hr after treatment with HgCl2, the renal concentration and burden of inorganic mercury decreased markedly in both normal and NPX rats during the 24 hr after the first dose of the respective chelating agent was administered. Treatment with DMPS was more effective than treatment with DMSA in reducing the renal burden of mercury in both groups of rats. The fall in the renal concentration and burden of mercury in both normal and NPX rats was due primarily to a decrease in the content of mercury in the renal cortex and outer stripe of the outer medulla. However, the decrease in the concentration of inorganic mercury in the outer stripe was significantly greater in NPX rats than in normal rats. Both chelating agents caused urinary excretion of mercury to increase significantly in normal and NPX rats. In association with the increased renal release of mercury in NPX rats, the urinary excretion of mercury per gram of kidney was significantly greater in NPX rats than in normal rats. These data indicate that the renal handling of DMPS and DMSA may be altered significantly after a substantial reduction in renal mass. Findings from the present study also show that treatment with DMPS, but not with DMSA, causes the content of mercury in the liver and cellular fraction of blood to decrease in normal and NPX rats. These findings indicate that there are significant differences in the extrarenal handling of these two chelating agents. The findings in the present study suggest that DMPS and DMSA are very effective agents in reducing the renal (and whole body) burden of inorganic mercury in normal and NPX rats.

Mercury clearance from human plasma during in vitro dialysis: screening systems for chelating agents.

Two in vitro systems were evaluated as potential screening methods for determining the most effective chelating agents for use in patients with inorganic mercury poisoning undergoing hemodialysis. The first system consisted of an in vitro clinical hemodialysis unit and the second system consisted of an in vitro equilibrium dialysis procedure. Both systems utilized pooled human plasma. Ten chelating agents were evaluated in these systems to determine their ability to enhance mercury clearance from human plasma. In the absence of chelators, plasma clearance of mercury was negligible. Of the chelating agents tested, 2,3-dimercaptopropanolol, which enhances biliary and fecal excretion of mercury poisoning, and dithiothreitol did not enhance mercury clearance at 90 min in the hemodialysis system. N-acetylcysteine appeared to be the most effective chelating agent of those tested in the hemodialysis system. N-acetylcysteine produced a 73% decrease in perfusate mercury concentration at 90 min. The results of equilibrium dialysis mirrored those of the hemodialysis in that N-acetylcysteine significantly enhanced mercury transfer across the dialysis membrane into the dialysate whereas dithiothreitol did not. If in vivo experiments confirm the present findings, then in vitro dialysis from pooled human plasma either using a standard clinical hemodialyzer or equilibrium dialysis system will be useful screening tools. Our results suggest that equilibrium dialysis may be a convenient and cost effective method to screen potential chelating agents as complementary to hemodialysis for the treatment of inorganic mercury poisoning.

A comparison of the effects of sodium selenite and seleno-L-methionine on disposition of orally administered mercuric chloride.

Previous studies demonstrated extensive effects of the administration of selenite on the biokinetics of simultaneously injected inorganic mercury. As the results of simultaneous administration might well be of questionable value for the assessment of the interaction between mercury and selenium during the long-term exposures relevant for human beings, the present study was performed. The purpose of the present study was to compare the effects of prolonged oral exposure to sodium selenite and seleno-L-methionine (7.5, 37.5, or 75 mumol/L drinking water) on the biokinetics of a single oral dose of 203Hg-labelled mercuric chloride (5 or 25 mumol/kg b.w.) in mice. Both selenium compounds caused a dose-dependent decrease in the excretion of absorbed mercury, as indicated by a 2-7 fold increase in whole-body retention of mercury. Selenite caused a significantly higher whole-body retention of mercury at day 14 than did seleno-L-methionine. Both selenium compounds affected the relative deposition of mercury in most organs, but the effect depended on the type of selenium compound, on the dose of mercury as well as on the molar ratio between mercury and the selenium compound. The amounts of mercury deposited in the liver, kidneys and spleen increased, whereas the amounts deposited in the uteri and the brain were unaffected by the selenium supplementation. Significant differences in relative organ deposition of mercury between mice given selenite and mice given seleno-L-methionine were observed in the stomach, intestinal tract and the kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Difference in effect of sodium selenite on mercury distributions after duodenal administration of mercuric chloride and mercuric oxide.

To obtain evidence for difference in the absorptive forms of HgCl2 and HgO from duodenum, the Hg distributions after the duodenal administration of HgCl2 and HgO and the effect of Na2SeO3 on their Hg distributions were compared. The Hg concentrations in erythrocytes and liver 2 hr after the administration of HgCl2 were significantly lower and higher than those of HgO, respectively, but their Hg distributions at 3.5 or 5 hr became identical. The administration of Na2SeO3 (intravenously) 2 hr after the administration of HgCl2 and HgO resulted in significant differences in their Hg concentrations in plasma, erythrocytes and kidney at 3.5 or 5 hr. These results suggest that the absorptive form of HgCl2 from the duodenum differs from that of HgO and this difference is a cause for the marked difference in effect of Na2SeO3 on the Hg distributions of HgCl2 and HgO.

Mercury-selenium interaction: distribution and excretion of 203Hg2+ in rats after simultaneous administration of selenite or selenate.

In female rats intravenously injected with 203HgCl2 (0.6 mg Hg2+ per kg body wt.) the effect of intraperitoneal administration of selenite or selenate (0.525 mg Se per kg body wt.) on distribution and excretion of 203Hg was studied. The content of 203Hg was lower in kidney and higher in liver and blood in the groups treated with selenate or selenite when compared with rats which received only mercury. The brain content of 203Hg was significantly increased in rats injected with selenite. Both selenium compounds injected immediately after mercury significantly decreased urinary as well as biliary excretion of 203Hg. A transient increase in the rate of biliary excretion of 203Hg during the first 2 h after administration was observed in rats treated with selenate. This finding seems to support the idea that the reduction of selenate to selenite in the body is not rapid but takes at least several hours.

Do selenium and glutathione inhibit the toxic effects of mercury in marine lamellibranchs?

The effect of selenium (SeO2) and glutathione (GSH) on the bioaccumulation of mercury (HgCl2) and on the activities of lysosomal enzymes in four species of tropical estuarine lamellibranchs is reported. A definite correlation between mercury levels in the external medium and tissue uptake and physiological behaviour--opening and closing of shell valves, response to mechanical stimulus, mucus secretion, and incidence of bleeding--was evident. In the clams exposed to Hg (range 0.1-5.0 mg l-1), bioaccumulation was dependent on the ambient concentration of Hg. The highest bioaccumulation of Hg occurred during the initial 24 h exposure period. Further exposure of up to 7 days did not increase the body burden of Hg. Of the four bivalve species exposed to 0.1 mg Hg l-1, Perna viridis showed the highest levels of Hg (approximately 47 ppm) followed by Anadara granosa, A. rhombea (approximately 25 ppm) and Meretrix casta (approximately 9 ppm). The uptake of Hg by A. granosa was greatly reduced by GSH, whereas Se enhanced it by 50% when administered in combination with Hg. However, the presence of Hg did not influence the uptake of Se. Exposure to combined GSH and Hg resulted in almost complete inhibition of Hg uptake in all four bivalve species. Prior exposure to GSH, however, did not have the same influence on their uptake of Hg. Nevertheless, exposure of clams to GSH following initial exposure to Hg resulted in complete depuration of accumulated Hg. The activities of lysosomal enzymes--arylsulfatase, acid phosphatase, beta-galactosidase and beta-glucuronidase--varied considerably. Treatment with Hg and GSH, separately and in combination, significantly enhanced the levels of beta-galactosidase (P less than 0.05) and beta-glucuronidase (P less than 0.001) in the digestive gland after 96 h exposure. Although Se increased beta-glucuronidase activity (P less than 0.001), it had no effect on beta-galactosidase. On exposure to Hg + Se the activity of both enzymes decreased, except in P. viridis where it increased by 39%. The results show unequivocally that Se does not offer any protection against the toxic effects of mercury in marine lamellibranchs, whereas in many marine vertebrates it does. GSH, a thiol-rich tripeptide, on the other hand, completely nullifies the toxic effects of Hg, both in vivo and in vitro.

Acute mercury chloride intoxication. Effects of hemodialysis and plasma exchange on mercury kinetic.

A 27 year-old man developed after ingestion of mercury chloride, 6 g, a hypovolemic shock, an acute renal failure and a necrosis of the stomach which required a total gastrectomy. The anuria did not improve and required 42 hemodialyses. Subsequent evolution showed numerous complications and the patient died on the 91st day. On admission mercury plasma concentration was 5 mg/L and decreased slowly with an apparent half-life of 226 hours. Hemodialyses were ineffective for mercury elimination: mercury clearances varied between -10 and + 1.5 ml/min. Seventeen mg of mercury were removed by six plasma exchanges: the mercury clearance was mean 17.3 ml/min. Among the extracorporeal elimination methods, plasma exchange appears to be the most efficient for inorganic mercury and it could be usefull in association with chelation therapy at the early phase of the intoxication.