Co-administration of Selenium with Inorganic Mercury Alters the Disposition of Mercuric Ions in Rats.

Mercury (Hg) is a common environmental toxicant to which humans are exposed regularly through occupational and dietary means. Although selenium supplementation has been reported to prevent the toxic effects of Hg in animals, the mechanisms for this prevention are not well understood. The purpose of the current study was to determine the effects of selenium on the disposition and toxicity of Hg. Wistar rats were injected intravenously with a non-nephrotoxic dose (0.5 µmol kg-1) or a nephrotoxic dose (2.5 µmol kg-1) of HgCl2 (containing radioactive Hg) with or without co-administration of sodium selenite (Na2SeO3). Twenty-four hours after exposure, rats were euthanized, and organs were harvested. Co-administration of SeO32- with HgCl2 reduced the renal burden of Hg and the urinary excretion of Hg while increasing the amount of Hg in blood and spleen. We propose that Hg reacts with reduced selenite in the blood to form large Hg-Se complexes that are unable to be filtered at the glomerulus. Consequently, these complexes remain in the blood and are able to accumulate in blood-rich organs. These complexes, which may have fewer toxic effects than other species of Hg, may be eliminated slowly over the course of weeks to months.

Effects of diphenyl diselenide diet on a model of mercury poisoning.

This work investigated the preventive effect of diphenyl diselenide [(PhSe)2] against the toxic effects of mercury in silver catfish (Rhamdia quelen). The animals were treated during 30 consecutive days with a (PhSe)2 supplemented feed (3.0 mg kg-1) or commercial feed. During the last 5 days the animals received a daily intraperitoneal dose of HgCl2 (1.7 mg kg-1) or Saline (0.9%). Twenty-four hours after the last HgCl2 injection, the animals were euthanized by spinal cord section to biological material obtainment. Hepatic (AST and ALT) and renal (ammonia and creatinine) toxicity biomarkers, δ-ALA-D activity, TBARS, total and non-protein thiols levels and hepatic, renal and blood mercury (Hg) and zinc (Zn) content were evaluated. Considering renal parameters, HgCl2 exposition increased serum creatinine levels and decreased δ-ALA-D activity, total and non-protein thiols and TBARS levels. HgCl2 exposure also decreased blood δ-ALA-D activity. With exception of blood δ-ALA-D activity and total thiols levels, (PhSe)2 supplementation partially prevented mercury induced alterations. Animals exposed to HgCl2 presented an increase in liver and kidney Hg content and a decrease in liver and blood Zn content. The alteration in blood Zn content was partially prevented with (PhSe)2 supplementation. With the exception of mercury and zinc content, no effects of HgCl2 exposure on hepatic tissue were observed. These results show that (PhSe)2 supplementation can represent a promising alternative to prevent the toxic effects presented by Hg exposure.

Zuotai and HgS differ from HgCl2 and methyl mercury in Hg accumulation and toxicity in weanling and aged rats.

Mercury sulfides are used in Ayurvedic medicines, Tibetan medicines, and Chinese medicines for thousands of years and are still used today. Cinnabar (α-HgS) and metacinnabar (ß-HgS) are different from mercury chloride (HgCl2) and methylmercury (MeHg) in their disposition and toxicity. Whether such scenario applies to weanling and aged animals is not known. To address this question, weanling (21d) and aged (450d) rats were orally given Zuotai (54% ß-HgS, 30mg/kg), HgS (α-HgS, 30mg/kg), HgCl2 (34.6mg/kg), or MeHg (MeHgCl, 3.2mg/kg) for 7days. Accumulation of Hg in kidney and liver, and the toxicity-sensitive gene expressions were examined. Animal body weight gain was decreased by HgCl2 and to a lesser extent by MeHg, but unaltered after Zuotai and HgS. HgCl2 and MeHg produced dramatic tissue Hg accumulation, increased kidney (kim-1 and Ngal) and liver (Ho-1) injury-sensitive gene expressions, but such changes are absent or mild after Zuotai and HgS. Aged rats were more susceptible than weanling rats to Hg toxicity. To examine roles of transporters in Hg accumulation, transporter gene expressions were examined. The expression of renal uptake transporters Oat1, Oct2, and Oatp4c1 and hepatic Oatp2 was decreased, while the expression of renal efflux transporter Mrp2, Mrp4 and Mdr1b was increased following HgCl2 and MeHg, but unaffected by Zuotai and HgS. Thus, Zuotai and HgS differ from HgCl2 and MeHg in producing tissue Hg accumulation and toxicity, and aged rats are more susceptible than weanling rats. Transporter expression could be adaptive means to reduce tissue Hg burden.

Selenium-binding protein 1: a sensitive urinary biomarker to detect heavy metal-induced nephrotoxicity.

Identifying novel biomarkers to detect nephrotoxicity is clinically important. Here, we attempted to identify new biomarkers for mercury-induced nephrotoxicity and compared their sensitivity to that of traditional biomarkers in animal models. Comparative proteomics analysis was performed in kidney tissues of Sprague-Dawley rats after oral treatment with HgCl2 (0.1, 1, or 5 mg/kg/day) for 21 days. Kidney cortex tissues were analyzed by two-dimensional gel electrophoresis/matrix-assisted laser desorption/ionization, and differentially expressed proteins were identified. The corresponding spots were quantitated by RT-PCR. Selenium-binding protein 1 (SBP1) was found to be the most markedly upregulated protein in the kidney cortex of rats after HgCl2 administration. However, blood urea nitrogen, serum creatinine, and glucose levels increased significantly only in the 1 or 5 mg/kg HgCl2-treated groups. A number of urinary excretion proteins, including kidney injury molecule-1, clusterin, monocyte chemoattractant protein-1, and ß-microglobulin, increased dose-dependently. Histopathological examination revealed severe proximal tubular damage in high-dose (5 mg/kg) HgCl2-exposed groups. In addition, urinary excretion of SBP1 significantly increased in a dose-dependent manner. To confirm the critical role of SBP1 as a biomarker for nephrotoxicity, normal kidney proximal tubular cells were treated with HgCl2, CdCl2, or cisplatin for 24 h. SBP1 levels significantly increased in conditioned media exposed to nephrotoxicants, but decreased in cell lysates. Our investigations suggest that SBP1 may play a critical role in the pathological processes underlying chemical-induced nephrotoxicity. Thus, urinary excretion of SBP1 might be a sensitive and specific biomarker to detect early stages of kidney injury.

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.

Ameliorative effect of certain antioxidants against mercury induced genotoxicity in peripheral blood lymphocytes.

Various antioxidants play an important role in reducing the reactive oxygen species (ROS) by scavenging them directly or indirectly. Mercury (Hg) is one of the known hazardous genotoxicant, induces the genotoxicity by enhancing the ROS. In the present study, three structurally different bioactive compounds such as melatonin (0.2 mM), curcumin (3.87 µM) and andrographolide (0.4 µM) were evaluated against the genotoxic effect of mercury. All the experiments were conducted using the peripheral blood lymphocytes In Vitro. The cultures were exposed to different doses (2.63 µM; 6.57 µM; 10.52 µM) of mercury salt (HgCl2) for studying various genotoxic indices. All three antioxidant compounds, alone and in combination with high dose of mercury, were added to the cultures with controls. For ascertaining genotoxicity, sister chromatid exchanges (SCEs), cell cycle proliferative index/replicative index (CCPI/RI), average generation time (AGT), population doubling time (PDT), %M1, %M2 and %M3 were assessed and analyzed using suitable statistical analysis. The results revealed a dose dependent increase in SCEs, AGT and PDT, with a concomitant reduction in CCPI values after treatment of mercury. Supplementation of these three antioxidant compounds effectively negated these genotoxic endpoints in treated cultures with improvement in the cell cycle kinetics i.e. CCPI. The antimutagenic activity of these compounds on mercury induced genotoxicity was in the following order: melatonin > curcumin > andrographolide. In conclusion, these compounds have ameliorated mercury induced increase in genotoxic indices due to their excellent antioxidant properties and the combination seems to be effective.

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.

Pomegranate (Punica granatum) peel extract provides protection against mercuric chloride-induced oxidative stress in Wistar strain rats.

CONTEXT: Pomegranate [Punica granatum L. (Lythraceae)] is rich in antioxidants. OBJECTIVE: The present work was undertaken to evaluate the protective effects of methanol extract of pomegranate peel extract (PPE) against a rat model of oxidative stress generated by treatment with mercuric chloride (HgCl(2)). MATERIALS AND METHODS: Rats were injected with HgCl(2) (5 mg/kg body weight in 0.9% NaCl) for developing oxidative stress. The methanol extract of pomegranate peel (PPE) was suspended in 0.5% sodium carboxymethylcellulose and fed to rats at 50 mg/kg body weight/day up to 30 days after HgCl(2) treatment. Biomarkers of oxidative stress including erythrocyte plasma membrane redox system (PMRS), lipid peroxidation, advanced oxidation protein products (AOPP), intracellular glutathione, and plasma antioxidant capacity as FRAP values were measured after PPE supplementation. RESULTS: HgCl(2)-treated rats showed increased oxidative stress as evidenced by increased activity of erythrocyte PMRS 153%, lipid peroxidation 31%, and AOPP 290%. There was a significant (p < 0.01) decrease (25%) in plasma antioxidant capacity and intracellular glutathione (75%). Supplementation with PPE protected rats from HgCl(2) induced oxidative damage. PPE supplementation to control rats increased antioxidant defense. DISCUSSION AND CONCLUSION: The results clearly demonstrate that PPE treatment augments the antioxidant defense mechanism in mercuric chloride-induced oxidant toxicity. To the best of our knowledge this is the first report of the increase in erythrocyte PMRS activity in rats after supplementation with any kind of antioxidant supplementation. This study emphasizes the need for characterizing PPE for potential unknown antioxidant compounds.

Hyperintense lesions in brain MRI after exposure to a mercuric chloride-containing skin whitening cream.

Exposure to inorganic mercury (Hg) is a serious problem presenting with a combination of neurological and psychiatric symptoms along with weight loss, pruritus, erythema, arterial hypertension, tachycardia, and renal tubular dysfunction. We report a 4-year-old girl with chronic intoxication of inorganic mercury secondary to the accidental use of an Hg2Cl2- and HgCl2-containing skin whitening cream (urine level of Hg, 41.1 µg/l; reference level, < 25 µg/l). Under treatment with dimercapto-1-propansulficacid, Hg level in the urine raised to 1,175.5 µg/l, neurological deterioration occurred, and brain magnetic resonance imaging (MRI) showed on fluid attenuated inversion recovery sequences new hyperintense lesions in the subcortical white matter. After 4 months, clinical signs and symptoms and brain MRI findings resolved. This is a first case of inorganic mercury poisoning showing hyperintense lesions in brain MRI and confirms earlier cases showing transient deterioration during chelation therapy. Although urinary excretion could be enhanced during chelation therapy, signs and symptoms of intoxication could be worsened.

[Comparative toxicology study of Cinnabar, Zhusha Anshenwan, methylmercury and mercuric chloride].

OBJECTIVE: To study the toxicity of Cinnabar and Cinnabar-containing traditional medicines (Zhusha Anshenwan) comparable to common mercurials. METHOD: The toxicity of methylmercury (MeHg), mercuric chloride (HgCl2), Cinnabar and Zhusha Anshenwan was studied in cultured human liver HL-7702 cells and in mice following acute and subacute exposures. RESULT: The 50% lethal concentrations (LC50) of MeHg, HgCl2, Cinnabar and Zhusha Anshenwan in human liver HL-7702 cells were 4.4, 9.2, 2460, 4050 mg x L(-1), respectively . Oral cinnabar at a dose of 20 g x kg(-1) (clinical dosage 250 times) did not kill mouse, but no mouse could survive MeHg at a dose of 0.1 g x kg(-1) or HgCl2 at a dose of 0. 15 g x kg(-1). Subacute toxicity experiment indicated that HgCl2 retarded body weight gain with significant accumulation of Hg in the liver and kidney. In comparison, mercury accumulation after Cinnabar and Zhusha Anshenwan was insignificant. No apparent hepatic and renal dysfunctions were evident under the experimental conditions, but the metallothionein-2 mRNA levels were much higher in HgCl2 group than in other groups. CONCLUSION: Cinnabar and Zhusha Anshenwan are much less toxic than MeHg and HgCl2.

[Monitoring early toxicity of heavy metals including Hg using a HSE-SEAP reporter gene].

OBJECTIVE: To develop a cellular assay based on heat shock signal pathway and secreted alkaline phosphatase (SEAP) reporter gene for investigating/predicting the early toxicity of heavy metals on HeLa cells in Chinese traditional medicine (TCM). METHOD: The pHSE-SEAP plasmid was transfected into HeLa cells to build a HSE-SEAP-HeLa cell model. For validation of the model, the transfected cells were treated by either heating at 42 degrees C for 1 h or incubated with 5 mol x L(-1) CdCl2 for 4 h. Then the cells were covered in complete DMEM culture medium for 48 h and the activity of SEAP (reflecting the cellular level of heat shock protein) in cultural supernatants was measured; meanwhile, cell viability was determined by MTT assays. In addition, the cells were treated by four mercury compounds, HgCl2, merthilate sodium, HgS and cinnabar at the sub-lethal concentrations (determined by MTT assays). Then the heat shock response was detected likewise. RESULT: Significant level of secreted alkaline phosphatase (SEAP) was found in pHSE-SEAP transfected HeLa cells treated either by heating (42 degrees C) or incubating with CdCl2. The heat shock protein was induced by CdCl2 before decrease of cell viability was observed. All four mercury compounds induced heat shock response in both time and concentration-dependant manner. However, there were big differences among the mercury compounds, suggesting potential differences for early-stage toxicity in vivo. CONCLUSION: The pHSE-SEAP transfected HeLa cells respond effectively to heat shock and metal stresses, and therefore provide a practical and repeatable assay for investigating/predicting the early toxicity of heavy metals and mineral-containing drugs in TCM.

Catabolic fate of dietary trilinoleoylglycerol hydroperoxides in rat gastrointestines.

To elucidate whether dietary lipid peroxides are absorbed in the body, the catabolic fate of trilinoleoylglycerol hydroperoxides (TL-OOH), in the gastrointestines of rats was examined. Oxidized trilinoleoylglycerol with a peroxide value of 1000 meq/kg, 0.5 or 20 mg, was dosed intragastrically to rat together with 59.5 or 40 mg unoxidized trilinoleoylglycerol, respectively. The fate of TL-OOH in gastric and intestinal lumina was determined by high-performance liquid chromatography periodically until 240 min after treatment. At low dose, TL-OOH was soon broken down to linoleic acid hydroperoxides (LA-OOH) and hydroxyls, probably through gastric lipases, whereas at high dose, TL-OOH was retained in the stomach. In both cases, TL-OOH did not reach the intestines, though the unoxidized lipids moved to the intestines. When LA-OOH was given intragastrically, the lipids decomposed in the stomach, and linoleic acid hydroxyls, hexanal, 9-oxononanoic acid, and two novel compounds were detected 30 min after treatment. The novel compounds were identified to be epoxyketones, 11-oxo-12,13-epoxy-9- and 11-oxo-9,10-epoxy-12-octadecenoic acids. Thus, dietary TL-OOH was broken down in the stomach releasing, LA-OOH which decomposed further, and did not reach the intestines.

Effect of acute administration of mercuric chloride on the disposition of copper, zinc, and iron in the rat.

The present study was designed to investigate the effect of mercuric chloride administration on copper, zinc, and iron concentrations in the liver, kidney, lung, heart, spleen, and muscle of rats. The results showed that after dose and time exposure to mercuric chloride, the concentration of mercury in the six tissues was significantly elevated. Data showed that there were no interaction between mercury and tissue iron. There was a considerable elevation of the content of copper in the kidney and liver. The most significant changes in the copper concentration took place in the kidneys. About a twofold increase in the copper content of the kidney was noted after exposure to mercuric chloride (3 mg and 5 mg/kg). Only slight elevations in the copper content occurred in the liver especially in high dose and longer exposure time. In the remaining organs, the copper content was not changed significantly (p > 0.05). The most significant changes in the zinc concentration took place in liver, kidney, lung and heart (5 mg/kg). Marked changes in kidney zinc concentrations were observed at any of the specified doses. Zinc concentrations were significantly increased in kidney of rats sacrificed 9-48 h after s.c. injection of HgCl2 (5 mg/kg); in liver obtained from rats at 18, 24 or 48 h after injection; and in lung after 24 or 48 h of treatment. The heart and spleen zinc concentrations were elevated at 24 and 48 h after injection of HgCl2 (5 mg/kg), respectively. The results of this study implicate that effects on copper and zinc concentrations of the target tissues of mercury may play an important role in the pathogenesis of acute mercuric chloride intoxication.

Utilization of renal slices to evaluate the efficacy of chelating agents for removing mercury from the kidney.

Mercury is an environmental contaminant that preferentially accumulates in the kidney. It has been previously shown using proton-induced X-ray emission analysis that mercury (HgCl2) accumulated in precision-cut rabbit renal cortical slices. In this study, the efficacy of seven chelating agents for the removal of Hg from renal slices has been examined. Rabbits were injected with HgCl2 (10 mg/kg) and 3 h later kidneys were sliced, or renal slices were exposed in vitro to a mildly toxic concentration of HgCl2 (5 x 10(-5)M, 4 h). The slices were then treated in vitro with 10 mM concentrations of EDTA, lipoic acid (LA), penicillamine (PA), glutathione (GSH), 1,4-dithiothreitol (DTT), DMSA, or DMPS. DMPS proved to be the most effective in mobilizing Hg from in vivo or in vitro HgCl2-exposed renal tissue ( > 85% of control after 3 h incubation). Relative efficacies for the seven agents were DMPS > DMSA, PA > DTT, GSH > LA, EDTA. The use of renal slices appears to be a useful in vitro tool for assessing the efficacy of chelating agents on mobilizing accumulated Hg from renal tissue.

Similarities of the in vivo and in vitro effects of mercuric chloride on [3H]ouabain binding and potassium activation of Na+/K(+)-ATPase in isolated rat cerebral microvessels.

A previous study revealed that a single i.p. administration of 6 mg/kg body wt. of mercuric chloride (MC) durably inhibits the rat cerebral microvascular Na+/K(+)-ATPase activity [1]. In this study, cerebral microvessels isolated 18 h after MC treatment were compared to those obtained from control rats and subsequently treated or not treated with MC in vitro, with regard to: (a) [3H]ouabain binding to, and (b) K(+)-activation kinetics of, the Na+/K(+)-ATPase. Microvessels from MC-treated rats showed a decrease of [3H]ouabain binding down to 62% of the control binding, and the same degree of inhibition was attained in microvessels treated in vitro with 5 microM MC. Analysis of the K(+)-activation kinetics of Na+/K(+)-ATPase revealed a decrease of Vmax from the control value of 13.1 to 7.67 mumol/mg/h in microvessels from MC-treated rats and 6.07 mumol/mg/h in microvessels treated in vitro with 5 microM MC, with no change in Km in either case. The similarity of the effects of in vivo and in vitro treatments suggests that the inhibition of the cerebromicrovascular Na+/K(+)-ATPase following in vivo administration of MC results from a direct interaction of Hg2+ with the enzyme.

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.

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.

[Studies on the behavior of mercury and selenium in blood of mice injected with those elements].

Male ddY mice were only once treated with, 1) mercuric chloride or methylmercuric chloride (20 mumol/kg, i.p., respectively) and various doses of sodium selenite (5, 20, and 40 mumol/kg, s.c., respectively) at the same time, 2) mercury compounds alone, and 3) various doses of sodium selenite alone. Then, the interaction between mercury and selenium was investigated in the blood and plasma at 1, 5, 24, 120, and 240 hr after injection. In mice receiving mercuric chloride and sodium selenite at the same time, the concentrations of mercury and selenium in the blood and plasma were markedly higher than those in mice receiving mercuric chloride or sodium selenite alone, especially at 1 and 5 hr after injection. In this case, mercury concentrations were increased depending on doses of sodium selenite. Furthermore, their decrement from 5 to 24 hr were markedly in groups with larger quantity of mercury accumulation. In the case of simultaneous injection of methylmercuric chloride and sodium selenite, the accumulation levels of mercury in the blood and plasma decreased by the simultaneous injection of selenium at 1 and 5 hr. The molar ratios of selenium to mercury in the blood and plasma simultaneously injected with mercuric chloride and sodium selenite were approx. 1 at 5 and 24 hr, independently of any change of sodium selenite doses. In gel filtration by Sephadex G-200 column of plasma of mice simultaneously injected mercuric chloride and sodium selenite, mercury reacted with selenium immediately after their injection, and the almost of them were bound and accumulated in the high-molecular weight fraction with the molar ratios (Se/Hg) of approx. 1 until about 24 hr after injection. After 24 hr of injection, however, the binding between mercury and selenium was significantly changed and their gel-filtration patterns were similar to those of each single dose group. These results suggested that mercury and selenium in the group of simultaneous injection of mercuric chloride and sodium selenite have different interaction in blood before and after 24 hr of injection.