Simultaneous administration of sodium selenite and mercuric chloride decreases efficacy of DMSA and DMPS in mercury elimination in rats

Two chelating agents meso-2,3-dimercaptosuccinic acid (DMSA) and sodium 2,3-dimercapto-propane-1-sulphonate (DMPS) were tested for their efficiency in mercury removal from the body of rats in the presence and in the absence of selenium. Female Wistar rats were given a single intraperitoneal injection of mercuric chloride or an equimolar mixture of mercuric chloride and sodium selenite (1.5 micromol/kg body weight). The chelating agents were given orally, in excess (500 micromol DMSA/kg body weight; 300 micromol DMPS/kg body weight), 30 min after the administration of mercury and selenium. The animals were euthanized 24 h after the treatment and mercury in the kidney, liver, and 24 h urine was determined using cold vapour atomic absorption spectrometry (CV-AAS). The simultaneous administration of mercuric chloride and sodium selenite led to a redistribution of mercury in the organs, so that accumulation of mercury in the kidneys was decreased and in the liver increased. Selenite also caused decrease in the level of urinary mercury excretion. Both chelating agents were effective in mercury removal from the body, by increasing its urinary excretion. However, when animals were simultaneously treated with mercury and selenite, the rise of mercury excreted in the urine due to the treatment with chelating agents was lower when compared to animals receiving mercury without selenite. It is concluded that sodium selenite decreases the efficiency of DMSA and DMPS in mercury removal from the body of rats.     

Effect of dietary selenium on the metabolism of aflatoxin B1 in turkeys

To investigate the biochemical mechanism of the previously reported protective effect of dietary selenium against aflatoxin toxicity, the hepatic metabolism of aflatoxin B1 in turkey poults was examined at various dietary selenium concentrations. Diets were supplemented with 0.2, 2.0 or 4.0 ppm selenium (as sodium selenite) and 500 ng aflatoxin B1/g diet in an 18-day trial. Free and conjugated aflatoxin and metabolites were quantified using high-performance liquid chromatography. The proportion of liver aflatoxins in conjugated forms increased and the ratio of free aflatoxin B1/M1 decreased with increasing dietary selenium concentrations. These in vivo results provide evidence of selenium-induced enhancement of aflatoxin detoxification processes. In a similar experiment using 2.0 ppm selenium and 750 ng aflatoxin B1/g diet, the concentration of hepatic reduced glutathione, cytochrome P-450 and the activity of enzymes involved in the metabolism of aflatoxin B1 and glutathione were determined. Although the selenium supplement increased glutathione peroxidase activity, dietary selenium had no effect on reduced glutathione or cytochrome P-450 concentrations or on the activities of glutathione transferase E, glucuronyl transferase and cytochrome c reductase. These data indicate that the protective action of selenium is not mediated by an increase in glutathione availability for aflatoxin conjugation or by effects on the activities of these enzymes as measured in vitro.     

Protective effects of selenium on methimazole-induced anemia and oxidative stress in adult rats and their offspring

The present study investigates the potential ability of selenium, considered as an antioxidant with pharmacological property to alleviate oxidative stress and hematological parameter disorders induced by methimazole, an antithyroid drug. Pregnant Wistar rats were randomly divided into four groups of six each: group I served as negative control and received a standard diet; group II received 250 mg/L of methimazole in drinking water and a standard diet; group III received both methimazole (250 mg/L, orally) and selenium (0.5 mg/kg of diet) supplemented to the standard diet; group IV served as positive control and received a supplement of selenium in the diet (0.5 mg/kg of diet) as sodium selenite (Na(2)SeO(3)). Treatment was started from the 14th day of pregnancy until day 14 after delivery. Methimazole reduced the number of red blood cells, hemoglobin concentration and hematocrit in mothers and their pups. Besides, plasma iron, vitamins B(9), B(12), C and E levels were reduced. Lipid peroxidation increased, objectified by high malondialdehyde levels and lactate dehydrogenase activity in plasma, while glutathione, glutathione peroxidase, superoxide dismutase and catalase activities showed a significant decline. Co-administration of selenium through diet improved all the parameters cited above. It can be concluded that the administration of selenium alleviates methimazole-induced toxicity, thus demonstrating its antioxidant efficacy.     

Evaluating the protective effects of vitamin E and selenium on hematology and liver,lung and uterus histopathology of rabbits with cypermethrin toxicity

Abstract

The objective of this study was to determine the efficacy of vitamin E and selenium as protective agents against cypermethrin (CY)-induced toxicity by evaluating hematology parameters along with liver, lung and uterus histopathology of female rabbits. Thirty female rabbits were randomly divided into five equal groups with six animals in each group (designated A, B, C, D and E). Animals in group A were control animals that did not receive CY, vitamin E, nor selenium. Animals in groups B–E were injected intraperitoneally with CY at 75?mg/kg body weight once every5 days over a 32?day period, while animals in the control group received saline. Animals in group C were also given vitamin E (150?mg/kg b.wt) orally and animals in group D were given selenium (0.45?mg/kg b.wt) orally. Group E was given both vitamin E at a dose of 150?mg/kg and selenium at a dose of 0.45?mg/kg. In group B (CY only), the values of PCV were decreased at the 12th day of gestation when compared to group A. The mean value of PCV was significantly higher in group E on the 12 and 24th day when compared to the other groups. The mean values of hemoglobin (Hb) were not significantly different among groups on the 12th and 24th day of gestation. On the 12th day of the gestation period, there were nonsignificant differences in the total number of erythrocytes among all the groups. However, on the 24thdayof the gestation period, there was a significant decrease in the total number of erythrocytes in group B compared to the control group. Total leukocytes were also increased in the animals of group B on the 12th day of gestation, whereas the total leukocytes were increased on the 24th day of gestation in all groups (A–D) compared to control. Histopathological studies of tissues of liver, lungs and uterus revealed that CY altered the normal parenchyma of these tissues and this was partially ameliorated by the vitamin E and selenium treatments. In conclusion, combined use of vitamin E and selenium partially ameliorated the toxicity of CY in female rabbits.     

Interactions between mercuric chloride and sodium selenite on cultured rat cerebrum

Explants of rat cerebrum in culture were treated with toxic concentration of HgCl₂ of 1.10^?4 M and with varying concentrations of sodium selenite. Treatment with sodium selenite resulted in a reduced neurotoxicity of HgCl₂, a maximal effect being attained at a selenite concentration of 1.10^?5 M. However, 1.10^?5 M sodium selenite was itself toxic. In in vitro cell systems, the toxicity of either mercury or selenium is decreased in the presence of the other element.     

Subacute oral toxicity investigation of selenium nanoparticles and selenite in rats

Selenium (Se) nanoparticles have been proposed as food supplements. However, the particle formulation may exert unexpected toxicity. The aim was therefore to compare toxicity of low doses of Se nanoparticles and the dissolved, ionized Se species selenite. Female rats were dosed orally for 28?d with either: 0.05, 0.5, or 4?mg Se/kg body weight (bw)/day as 20?nm Se nanoparticles or 0.05 or 0.5?mg Se/kg bw/day as sodium selenite. Male rats were dosed 4?mg Se/kg bw/day as Se nanoparticles. Body weight and clinical appearance were recorded throughout the experiment. At necropsy, blood samples were taken for hematological and clinical chemistry analyses; organ weights were recorded. At the high-dose of Se nanoparticles, overt toxicity occurred and the female animals had to be euthanized prematurely, whereas the male animals were reduced in dose. At all doses of Se nanoparticles and at 0.5?mg Se/kg bw/day as selenite, a lower body weight gain as compared to vehicle occurred. Relative liver weight was increased for both Se formulations at 0.5?mg Se/kg bw/day. Creatinine clearance and urinary pH were affected in some Se dosed groups. There were no effects among dosed groups on brain neurotransmitters or on hematological parameters compared with controls. There were no histological changes in the livers of animals exposed to Se nanoparticles or to selenite. Based on effects on body weight and liver weight, selenium nanoparticles and ionic Se exerted similar toxicity. This suggests that a nanoparticle-specific toxicity of Se did not occur.     

Embryotoxicity and dose-response relationships of selenium in hamsters

Pregnant hamsters were treated with selenite, selenate, and selenomethionine during the critical stages of embryogenesis. The dosing regimens were oral, intravenous, and osmotic minipump infusion. Malformations, mainly encephaloceles, were noted with oral and intravenous selenite and selenate but were associated with maternal toxicity manifested by inanition and weight loss. Fetal body weights and lengths were reduced in a dose-dependent manner with the inorganic forms. Single oral doses of selenomethionine above 77 mumol/kg induced similar malformations but not when the dose was delivered orally over four days nor by minipump over several days. Fetal body weights and lengths were decreased by selenomethionine in a dose-dependent manner. Maternal toxicity was pronounced with the higher doses of selenomethionine. Assigning a specific teratogenic effect to selenium is confounded by maternal toxicity.     

Elemental selenium particles at nano-size (Nano-Se) are more toxic to Medaka (Oryzias latipes) as a consequence of hyper-accumulation of selenium: a comparison with sodium selenite

Recent studies have shown that elemental selenium particles at nano-size (Nano-Se) exhibited comparable bioavailability and less toxicity in mice and rats when compared to sodium selenite, selenomethinine and methylselenocysteine. However, little is known about the toxicity profile of Nano-Se in aquatic animals. In the present study, toxicities of Nano-Se and selenite in selenium-sufficient Medaka fish were compared. Selenium bioaccumulation and subsequent clearance in fish livers, gills, muscles and whole bodies were examined after 10 days of exposure to Nano-Se and selenite (100mug Se/L) and again after 7 days of depuration. Both forms of selenium exposure effectively increased selenium concentrations in the investigated tissues. Surprisingly, Nano-Se was found to be more hyper-accumulated in the liver compared to selenite with differences as high as sixfold. Selenium clearance of both Nano-Se and selenite occurred at similar ratios in whole bodies and muscles but was not rapidly cleared from livers and gills. Nano-Se exhibited strong toxicity for Medaka with an approximately fivefold difference in terms of LC(50) compared to selenite. Nano-Se also caused larger effects on oxidative stress, most likely due to more hyper-accumulation of selenium in liver. The present study suggests that toxicity of nanoparticles can largely vary between different species and concludes that the evaluation of nanotoxicology should be carried out on a case-by-case basis.     

Changes in distribution of mercury and selenium in soluble fractions of rabbit tissues after simultaneous administration

The existing states of mercury and selenium in the blood and in soluble fractions of perfused rabbit liver and kidney were studied by gel filtration on Sephadex G-200 1 hr or 24 hr after intravenous injection of mercuric chloride and/or sodium selenite. Both mercury and selenium in the plasma and stroma-free hemolysate were found to exist in the high-molecular weight fraction following simultaneous injection of mercuric chloride and sodium selenite. Patterns in gel filtration of the plasma and the stroma-free hemolysate did not show any significant change between 1 hr and 24 hr after the administration. A similar tendency as described above was obtained with the liver-soluble fraction at 24 hr after injection of mercuric chloride and sodium selenite. A possible role of the high-molecular weight complex, which is quickly formed by the interaction of mercury and selenium in blood stream, in decreasing the acute renal toxicity of inorganic mercury is discussed.     

硒对氯化汞免疫毒性的影响及其机理

采用免疫毒理学和生化毒理学方法，研究了亚硒酸钠对氯化汞免疫毒性的影响及作用机理。结果表明：氯化汞染毒的ＩＣＲ小鼠血中碳廓清率、ＳＲＢＣ致敏小鼠的ＤＴＨ反应、ＤＮＣＢ所致的ＤＣＨ反应、血清溶血素形成和免疫器官脏体比均明显低于对照组，预先投以亚硒酸钠后，再给同剂量的氯化汞的小鼠上述各指标都有不同程度提高。免疫器官脂质过氧化作用，汞组与对照组比较：脂质过氧化物含量明显升高，而谷胱甘肽过氧化物酶活性明显降低；硒汞组与汞组比较：脂质过氧化物含量明显降低，而谷胱甘肽过氧化物酶活性明显升高。上述结果提示：亚硒酸钠对氯化汞所致的免疫毒性和免疫器官的脂质过氧化损伤具有保护作用     

Formation and possible role of bis(methylmercuric) selenide in rats treated with methylmercury and selenite

The metabolic fate of methylmercury after administration of [²⁰³Hg]-methylmercuric chloride in combination with sodium selenite was investigated in rats. Whole body autoradiography and radioassay showed that administration of selenite decreased the mercury concentration in the liver and kidney, and increased that in the brain. The rapid changes of methylmercury concentration in the tissues after selenite injection were accompanied by increases in mercury extractable with benzene at neutral pH. The maximum levels of benzene-extractable mercury in the blood, kidney and liver were attained 30 min after selenite injection and were 30, 23 and 8 percent, respectively, of the total mercury. Thin-layer chromatography showed that the benzene-extractable mercury was a complex of methylmercury with selenium, bis(methylmercuric) selenide. These findings indicate that selenite alters the distribution of methylmercury in the tissues by formation of a diffusible complex with methylmercury, bis(methylmercuric) selenide.     

Short-term (6-week) oral toxicity study of selenium in Syrian hamsters

The subacute toxicity of selenium was tested by feeding sodium selenite to Syrian hamsters at dietary levels of 0.1, 1, 5, 10 and 20 ppm selenium for 42 days. General health, survival and organ weights were not adversely affected at any of the dose levels. Weight gain and food intake were relatively low in males fed the highest dose level. The differences from the control values were not statistically significant and there was no similar effect in females. Hamsters fed 10 or 20 ppm retained considerably higher levels of selenium in the liver than did the controls. Microscopic examination of the liver revealed degenerative changes in males and females in the 20-ppm group. The no-toxic-effect level of selenium fed in the diet for 42 days to Syrian hamsters was found to be 10 ppm, equivalent to an intake of about 0.7 mg selenium/kg body weight/day.     

Metallothionein induction by sodium selenite at two different ambient temperatures in mice

The induction of metallothionein (MT) synthesis by sodium selenite was investigated in mice with regard to the hypothermic response known to be caused by sodium selenite. Mice received a subcutaneous injection of sodium selenite at two doses (20 and 45 mol/kg) under two ambient temperature (22 and 33° C) conditions. Hepatic MT concentration was significantly increased by an injection of sodium selenite compared to the control, whereas no significant effect of ambient temperature was observed. The distribution of radiolabeled selenium was examined in vivo and in vitro. When sodium selenite was injected into mice, radiolabeled selenium was mostly eluted in a fraction larger in molecular weight than MT and was not found in a fraction corresponding to MT. When sodium selenite was added to the hepatic supernatant of the mice that had been injected with zinc sulfate, zinc in zinc-thionein was not displaced by radiolabeled selenium.     

The effect of sodium selenite supplementation on monensin-induced growth inhibition and residue accumulation in broiler chicks

Ninety-six commercial broiler chicks housed in battery brooders were exposed to experimental diets varying in monensin (50, 250 mg/kg) and sodium selenite (0, 10 mg/kg) levels from their 10th to 25th day of age. Feed and water were supplied ad libitum. There were 4 replications of each experimental treatment, each with 6 birds/replication. The data on bird weights showed a significant treatment effect for monensin, sodium selenite, and an interaction between the 2. High levels of monensin and sodium selenite decreased weight, the combination exacerbating this response. The residue data showed that chicks accumulated significantly higher concentrations of selenium in their tissues when on diets high in sodium selenite. Chicks also accumulated significantly higher concentrations of monensin in their tissues when on diets high in monensin. An interactive effect was observed in terms of the selenium residue data, high levels of dietary monensin decreased the selenium residue concentration in the liver, kidney and cardiac muscle tissues when on high sodium selenite diets. No interactive effect was observed in terms of the monensin residue data. Pathological lesions, which were expected but not observed, may also indicate an interaction between these compounds.     

Fumonisin B1-induced DNA damage in rat liver and spleen: effects of pretreatment with coenzyme Q10, L-carnitine, alpha-tocopherol and selenium.

Active oxygen radical species are reported to cause organ damage. This study was designed to determine whether oxidative stress contributed to the initiation or progression of hepatic and splenic cell DNA damage induced by fumonisin B1 (FB1) in rats. Another aim was to investigate the protective effects of the antioxidants coenzyme Q10 (CoQ10), L-carnitine, vitamin E (alpha-tocopherol) and selenium against DNA damage in the liver and spleen of rats treated with FB1. Fasted rats were injected intravenously with a single dose of fumonisin B1 at 1.55 mg kg-1 body wt. into the tail vein. Treatment with FB1 led to splenic and hepatic DNA fragmentation in 85% of the test animals. DNA fragmentation was investigated as a critical event in toxic cell death by testing total Ca2+ in liver. FB1 administration caused total Ca2+ in liver to increase within 4 h (204% of control). Measurement of liver enzyme activities showed an increase in aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT). FB1 also markedly decreased splenic and hepatic glutathione (GSH) levels. Pretreatment with CoQ10 (30 mg CoQ10 kg-1 diet) together with L-carnitine (2.8 mg carnitine kg-1 diet), alpha-tocopherol (30 IU vitamin E kg-1 diet) and selenium (1 mg selenium as sodium selenite kg-1 diet), decreased DNA damage and the activities of Ca2+, ASAT and ALAT in the liver. On the other hand, the level of GSH was slightly increased. The CoQ10 alone did not significantly protect against toxic cell death and glutathione depletion caused by FB1. Oxidative damage caused by FB1 may be one of the underlining mechanisms of FB1-induced cell injury and DNA damage.     

Antioxidant activity of ubiquinone-9 and its combinations with vitamin E and sodium selenite in toxic lesions of the liver

It was established that ubiquinone-9 (30 mg/kg per course) decreases in rats the content of primary products of lipid peroxidation--diene conjugates--in the liver by 12 times greater than vitamin E (a course dose of 30 mg/kg). Ubiquinone-9, vitamin E and sodium selenite (a course dose of 90 mg/kg) equally reduced the content of a secondary product of lipid peroxidation--malon dialdehyde. In this case the activity of sodium selenite was 300 times higher than the activity of ubiquinone-9 and vitamin E. The use of ubiquinone-9 in combination with vitamin E and sodium selenite potentiated the antioxidant effect.     

Effect of dietary co-administration of sodium selenite on sodium arsenite-induced ovarian and uterine disorders in mature albino rats.

The subchronic treatment of mature female Wistar-strain albino rats in diestrous phase with sodium arsenite at a dose of 0.4 ppm/100 g body weight/rat/day via drinking water for period of 28 days (seven estrous cycles) caused a significant reduction in the plasma levels of leutinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol along with a significant decrease in ovarian activities of delta five, 3 beta-hydroxysteroid dehydrogenase (Delta5,3beta-HSD), and 17 beta-hydroxysteroid dehydrogenase (17beta-HSD) followed by a reduction in ovarian and uterine peroxidase activities. A significant weight loss of the ovary and uterus was also observed after this treatment, along with a prolonged diestrous phase and a high accumulation of arsenic in the plasma and these organs. Moreover, sodium arsenite was also responsible for ovarian follicular and uterine cell degeneration characterized by a high number of regressing follicles and a reduction in the uterine luminal diameter, respectively, in comparison with the controls. A dietary supplementation of sodium selenite at the dose of 0.6 mg/100 g body weight/rat/day for a period of 28 days along with arsenic treatment minimized the gonadal weight loss significantly and increased the activities of the ovarian steroidogenic enzymes as well as the ovarian and uterine peroxidase at the control level. Selenium was also able to increase the plasma levels of LH, FSH, and estradiol toward the control level. Vaginal smears showed normal estrous cyclicity in sodium selenite-supplemented arsenic-treated rats along with lower arsenic levels in the plasma and gonadal tissue in comparison with arsenic-only-treated rats. Histological sections of ovary and uterine tissues in the control and experimental groups confirmed that sodium selenite supplementation was able to prevent arsenic-induced histopathological changes in the ovary and uterus. Plasma levels of norepinephrine and dopamine in the midbrain and diencephalon decreased significantly, whereas the serotonin level was increased significantly after 28 days of sodium arsenite treatment. All of these parameters were, in most cases, unchanged from the control level when sodium selenite was co-administered with sodium arsenite. Arsenic intoxication was also associated with increased liver weight and elevation in the activities of hepatic and renal acid phosphatase, alkaline phosphatase, and transaminases, but selenium co-administration was not able to change these toxic effects of arsenic. The results of our experiments indicate the significant protective action of sodium selenite on arsenic-induced toxicity in the female reproductive system, while there was no significant protective effect of selenium on arsenic-induced toxicity in other organs.     

Toxicity of nutritionally available selenium compounds in primary and transformed hepatocytes

The essential trace element selenium is also toxic at low doses. Since supplementation of selenium is discussed as cancer prophylaxis, we investigated whether or not bioavailable selenium compounds are selectively toxic on malignant cells by comparing primary and transformed liver cells as to the extent and mode of cell death. Sodium selenite and selenate exclusively induced necrosis in a concentration-dependent manner in all cell types investigated. In primary murine hepatocytes, the EC50 was 20 microM for selenite, 270 microM for selenate, and 30 microM for Se-methionine. In the human carcinoma cell line HepG2, the EC50 for selenite was 40 microM, and for selenate 1.1 mM, whereas Se-methionine was essentially non-toxic up to 10 mM. Similar results were found in murine Hepa1-6 cells. Exposure of primary murine cells to selenate or selenite resulted in increased lipid peroxidation. Toxicity was inhibited by superoxide dismutase plus catalase, indicating an important role for reactive oxygen intermediates. In primary hepatocytes, metabolical depletion of intracellular ATP by the ketohexose tagatose, significantly decreased the cytotoxicity of Se-methionine, while the one of selenite was increased. These data do not provide any in vitro evidence that bioavailable selenium compounds induce preferentially apoptotic cell death or selectively kill transformed hepatocytes.     

Effect of sodium selenite upon bromobenzene toxicity in rats. II. Metabolism

The effects of sodium selenite (12.5 or 30 mumol/kg, ip) upon bromobenzene metabolism were examined in male rats treated with selenite at 72 hr prior to bromobenzene exposure (7.5 mmol/kg, ip). The inhibitory nature of selenium treatment upon xenobiotic metabolism and increased production of hepatic thiol suggested that selenite might affect metabolic activation and detoxification of bromobenzene. Selenite treatment lowered in vivo covalent binding of [14C]bromobenzene while the in vitro covalent binding of [14C]bromobenzene in microsomes isolated from selenite-treated rats was unaffected compared to control. When the rate of [14C]bromobenzene decline in whole blood was evaluated in selenite-treated rats over 48 hr after bromobenzene administration, no significant differences were observed when compared to control. Furthermore, values of glutathione conjugates and hydroxylated metabolites of bromobenzene were similar in urine samples collected over 48 hr from selenite and control rats. Mechanistically, reduction of bromobenzene hepatotoxicity by selenite is not mediated through an altered metabolism of bromobenzene, but by alteration of cellular events occurring after metabolic activation.     

Effect of sodium selenite upon bromobenzene toxicity in rats. I. Hepatotoxicity

The effects of sodium selenite on bromobenzene hepatotoxicity were examined in male rats. Rats pretreated with sodium selenite (12.5 or 30 mumol/kg, ip) 72 hr prior to injection of bromobenzene (7.5 mmol/kg, ip) showed a marked reduction in bromobenzene-induced liver injury as evidenced by decreased plasma alanine and aspartate transaminase values, sorbitol dehydrogenase activity, and reduced histologic damage. Administration of bromobenzene did not affect the selenium content of blood or liver. At 72 hr after treatment with selenite, hepatic reduced (GSH) and oxidized (GSSG) glutathione values or GSH synthetic and degradation enzyme activities were not altered. However, from 3 to 12 hr following bromobenzene administration, hepatic GSH and cysteine amounts declined less rapidly in selenite-treated rats compared to control. Thus, acute selenite treatment ameliorated bromobenzene hepatotoxicity in a manner suggesting facilitation of hepatic GSH production by selenite for use in bromobenzene detoxication.