Rapid method for removal of inorganic mercury contained in methylmercury preparation using CM-Sephadex minicolumn.
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Chromatography, Ion Exchange↗
Biomedical subjects
A Naganuma
Publications and source records attributed to A Naganuma.
[Suppression of CDDP-induced renal toxicity by sodium selenite].
CDDP is a strong anti-cancer agent, but impairs renal function. Since the selenium has been known to reduce the renal toxicity of mercury, the effect of selenium on the adverse action of CDDP was examined in mice. Remarkable protective action of sodium selenite was demonstrated against lethal and renal toxicity of CDDP. Furthermore, addition of selenite did not impair the anti-cancer action of CDDP. Morphological diminution of renal damage by selenite was evident by light and electron microscopic study. The results suggest that selenite decreases renal toxicity of CDDP without impairing its anti-tumor action.
Animals↗
Species difference in biliary excretion of methylmercury.
Species difference in the biliary excretion of methylmercury was studied in male rats, mice, rabbits and guinea pigs. The rates of mercury excretion (% dose/2 hr) into the bile of the rats, mice, rabbits and guinea pigs during the 2 hr from 2 to 4 hr after the administration of methylmercury were 0.61, 0.091, 0.036 and 0.019, respectively. These results suggest that biliary excretion and enterohepatic circulation of methylmercury in the latter three species may not influence the fate of this compound as significantly as in rats. Most of the methylmercury excreted into the bile of rats was bound to glutathione (GSH). In the mouse bile, 40% of the methylmercury was bound to GSH and the rest was found in a fraction eluted at the void volume of the Sephadex G-15 column. However, in the case of the rabbits and guinea pigs, methylmercury-GSH was scarcely detectable in the bile and almost all of the methylmercury was eluted at the void volume of the column.
Animals↗
Normal organic and inorganic mercury levels in the human feto-placental system.
To clarify the normal metabolism of mercurials in the human feto-placental system, organic (or methyl) mercury and inorganic mercury were measured in maternal blood (MB), umbilical cord blood (UB), and chorionic tissues of the placenta (PC) and its blood vessels (PV), obtained from pregnant women just after delivery, as well as in fetal liver and fetal brain from induced abortion cases. Organic mercury was commonly detected in MB, UB, PC and PV, with slightly more elevated values in UB and PC than in MB, whereas inorganic mercury was detected in PC and PV, but not in MB and UB. In the fetal liver, 27-60% of mercury was in the form of inorganic mercury, whilst in four of five fetal brain samples, inorganic mercury was not detected. Additionally, fetal liver demethylation activity was studied in vitro. Incubation of methyl mercury with chopped fetal liver tissue for 24 h resulted in demethylation of approximately 1% of the methyl mercury.
Dealkylation↗
Effect of administration sequence of mercuric chloride and sodium selenite on their fates and toxicities in mice.
Interaction of mercury and selenium was examined in mice given mercuric chloride (25 mumol/kg) intravenously with sodium selenite (25 mumol/kg, iv) according to various administration schedules. Body weight of the mice given mercuric chloride or selenite alone did not increase, but the mice given both compounds simultaneously grew as well as control mice. On the other hand, only a 1-hr shift of administration of either compound canceled the mutual detoxifying effect. The most conspicuous changes in tissue distribution of mercury and selenium and in gel filtration patterns of both elements accumulating in tissues of the mice were observed when both compounds were administered simultaneously. These experimental results indicate that the interaction of mercuric mercury with selenite in mice occurred to the greatest extent upon simultaneous administration, supporting the hypothesis that the interaction primarily occurs in the blood stream.
Animals↗
Toxic effects of selenodiglutathione on pregnant mice.
A single dose of selenodiglutathione (GSSeSG) or sodium selenite (SS) was injected i.v. into pregnant CD-1 mice on day 12 of gestation at dosages varying from 16.4-32.0 mumol/kg body weight. Dose-dependent elevation of maternal death rates was observed for both treatments, and the slope of the dose-response curve was significantly steeper following GSSeSG treatment. However, fetotoxic effects were not different between the treatments.
Animals↗
Effect of selenite on renal toxicity and antitumor activity of cis-diamminedichloroplatinum in mice inoculated with Ehrlich ascites tumor cell.
Effect of sodium selenite on renal toxicity and antitumor activity of cis-diamminedichloroplatinum (Cisplatin; CDDP) repeatedly administered to mice inoculated with Ehrlich ascites tumor cells were examined. Simultaneous repeated administration of selenite with CDDP markedly improved the growth depression, the renal toxicity indicated by blood urea nitrogen value and the diarrhea caused by CDDP, and inhibited the growth of Ehrlich ascites tumor cells cooperatively with CDDP. This results suggest that selenium compounds are useful for prevention of the toxic side effects of CDDP.
Animals↗
Effect of time intervals of selenium administration after injection of mercuric chloride on toxicity and renal concentration of mercury in mice.
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Animals↗
Effect of copper pretreatment on toxicity and antitumor activity of cis-diamminedichloroplatinum in mice.
Effect of pretreatment with CuSO4 on toxicity and antitumor activity of cis-diamminedichloroplatinum (Cisplatin; CDDP) in mice were examined. Single subcutaneous administration of copper (CuSO4, 40 mumol/kg) 24 hr prior to injection of a lethal dose of CDDP (35 mumol/kg, sc) showed the most favorable effect among various administration conditions tested and completely prevented the manifestation of lethal toxicity of CDDP. In mice subcutaneously inoculated with Ehrlich tumor cells, the preadministration of copper also depressed the lethal and renal toxicity of CDDP without compromising its antitumor activity.
Animals↗
Mode of in vitro interaction of mercuric mercury with selenite to form high-molecular weight substance in rabbit blood.
Mode of interaction of mercuric mercury and selenite in rabbit blood was investigated in vitro. After the incubation of rabbit blood with 10(-5) M each of 203HgCl2 and Na2(75)SeO3, the amounts of both 203Hg and 75Se incorporated into erythrocytes were markedly larger than the case where the blood was treated separately with one of these compounds. Most of 203Hg and 75Se distributed into plasma and erythrocytes were found in high-molecular weight substance(s) (HMWS) fractionated by gel filtration at a molar ratio of 1:1. The 203Hg and 75Se in HMWS found in plasma and erythrocytes were hardly diffusable through the erythrocytes membrane. The formation of the HMWS containing mercury and selenium was observed in stroma-free hemolysate incubated with mercuric chloride and selenite, but not in plasma. Addition of reduced glutathione (GSH) to the plasma, however, gave the HMWS as reaction products containing equimolar amounts of mercury and selenium. Further the binding properties of selenium to proteins were studied in the plasma incubated with selenodiglutathione (GSSeSG) or with selenite in the presence of GSH. The results indicated that GSH, a cellular component, is essential for the formation of an active selenium compound from selenite and that the interaction of mercuric mercury and selenite in plasma in the presence of GSH may occur through the other mechanism than the formation of GSSeSG.
Animals↗
The interaction of selenium with various metals in vitro and in vivo.
The effects of many metal ions (Mn2+, Ag+, Cu+, Cu2+, Cd2+, Hg2+, Pb2+, Zn2+, As3+, Co2+, Bi3+, Ni2+, Sn2+, Sr2+, Fe2+, Fe3+, Ba2+, Mg2+, Cr3+, Cr6+, Pt2+, Au3+, Tl+, and Pd2+) on behavior of selenium in biological systems were examined in vitro and in vivo. In the in vitro studies using four different reaction systems, Mn2+, Ag+, Cu+, Cu2+, Cd2+, Hg2+, Pb2+, Zn2+, As3+, Co2+, Ni2+, Cr6+, Pt2+, Au3+, Tl+ and Pd2+ affected the behavior of selenium. Body distribution of selenium in mice was significantly altered by the i.v. coadministration of Ag+, Cu+, Cu2+, Cd2+, Hg2+, Pb2+, Zn2+, As3+, Bi3+, Ni2+, Cr3+, Pt2+, Au3+ or Pd2+. In the present study it was proved that the behavior of selenium in biological systems were influenced by many metals in vitro and in vivo. This observation is important in contemplating the biological roles of selenium as an essential element or as modifying factor for the toxicity of metal compounds.
Animals↗
Mercury distribution in mouse brain after i.v. administration of bis(methylmercuric) selenide.
The distribution of mercury in the brain of mice after i.v. administration of methylmercury, methylmercury with selenite, or bis(methylmercuric) selenide (BMS) was examined by whole-body autoradiography using 203Hg-labelled mercury compounds. The radioactivity in the brain of the mice that received methylmercury and selenite simultaneously, or BMS, was higher than that of the mice that received methylmercury alone, but the differences were not significant.
Animals↗
Changes in in vitro interaction profiles of mercuric mercury and selenite in rabbit blood under various reaction conditions.
In vitro interaction profiles of mercuric mercury and selenite in rabbit blood under various reaction conditions were investigated. The most remarkable changes in the incorporations into the erythrocytes and gel filtration profiles of mercury and selenium in blood were observed when 10(-5) M mercuric chloride and 10(-5) M selenite were added to rabbit blood. Under this conditions, the mercury and selenium added always behaved with each other on gel filtration suggesting that most of mercury and selenium existed in a complex at a molar ratio of 1. When the concentration of mercuric chloride was 10(-7) in blood, however, the incorporation of mercury into erythrocytes was also increased by the simultaneous addition of selenite, but 10(-7) mercury did not stimulate the selenium incorporation. The behaviors of mercury and selenium in blood were altered by the order of addition of mercuric chloride and selenite to the blood. Compared to the simultaneous addition of both compounds, the final amount of mercury and selenium incorporated into erythrocytes were reduced by the addition of mercuric chloride prior to selenite, whereas the rates of incorporation of mercury and selenium were lowered by the addition of selenite prior to mercury. The gel filtration patterns of mercury and selenium in the plasma and stroma-free hemolysate of the blood preincubated with selenite before the addition of mercury were different from the case of simultaneous addition of both compounds or addition of mercury prior to selenite. The variety of interaction profiles of mercuric mercury and selenium in blood under different reaction conditions as observed in the present in vitro study may reflect the complex modes of interaction actually occurs in vivo.
Animals↗
Selenium efficiently depressed toxic side effect of cis-diamminedichloroplatinum.
Effect of selenium on toxic side effects of cis-diamminedichloroplatinum (Cisplatin; CDDP) which is a potent anticancer drug containing platinum was examined. Remarkable protective effects of selenium against lethal and renal toxicity of CDDP were observed when selenite was administered to mice once a day after single injection of lethal dose of CDDP. On the other hand antitumor activity of CDDP was hardly depressed by selenite.
Animals↗
A reaction product from mercuric mercury, selenite and reduced glutathione.
Reaction of mercuric mercury and selenite in the presence of reduced glutathione (GSH) was studied. A black complex containing GSH and equimolar amounts of mercury and selenium was obtained by the reaction of sodium selenite and mercuric chloride in the presence of excess amounts of GSH. This complex was soluble in water, but insoluble in ethanol. Toxicity of the complex was very low in comparison with mercuric chloride or sodium selenite. Formation of such complex of lower toxicity in animals as described above may play an important role in the modification of toxicity of mercuric mercury by selenite.
Animals↗
Properties of mercury and selenium in a high-molecular weight substance in rabbit tissues formed by simultaneous administration.
The properties of mercury and selenium existing in high-molecular weight substance(s) (HMWS) obtained from plasma, stroma-free hemolysate, soluble and insoluble fractions of the liver of rabbits dosed with mercuric chloride and selenite were studied. Analytical procedures--gel filtration, ion exchange chromatography, and sucrose density gradient ultracentrifugation--showed that equimolar amounts of mercury and selenium were present in HMWS in the blood and the liver. Dialysis against mercaptoethanol suggested that selenium and mercury were tightly bound to HMWS in the liver soluble fraction. The formation of the HMWS may contribute to reducing the toxicity of both mercury and selenium. Since mercury and selenium in HMWS in the blood and the liver were present in smaller fragments after trypsin digestion, these HMWS appeared to be protein associated with mercury and selenium. However, after exhaustive digestion with Pronase, mercury and selenium in HMWS were rendered insoluble. The above process appears to take in the body of rabbits after simultaneous administration of mercury and selenium, because the livers excised from these rabbits were found to contain iso-molar and sodium dodecyl sulfate-insoluble selenium and mercury which increased in amount with time.
Animals↗
Behavior of inorganic mercury and selenium in insoluble fractions of rabbit tissues after simultaneous administration.
The existing states of mercury and selenium in the insoluble fractions of perfused rabbit liver and kidney were studied by gel filtration on Sephadex G-200 at 24 h after i.v. injection of mercuric chloride and/or sodium selenite. After simultaneous injection of mercuric chloride and selenite, both mercury and selenium existed in a high-molecular weight (HMW) fraction of the liver-insoluble fraction at a molar ratio of 1:1, there was little change in gel filtration pattern of the kidney-insoluble fraction. Equimolar amounts of mercury and selenium existed in each subcellular fraction of rabbit liver. Most of the mercury and selenium accumulated in the rabbit liver, not only those in the soluble fraction but also those in the insoluble fraction, appeared to co-exist in the HMW fraction at a molar ratio of 1:1 at 24 h after simultaneous administration.
Animals↗
Effects of sodium selenite on distribution and placental transfer of mercuric mercury in mice of late gestational period.
Mercury distribution and placental transfer in mice were investigated with coadministration of selenite. Pregnant mice, subcutaneously injected with 1.5 or 15.0 mumol/kg of mercuric chloride and 0, 1.3, 12.7 or 25.3 mumol/kg of sodium selenite on day 16 or their gestation, were examined for tissue distribution of mercury 24 hours after treatment. Elevated mercury concentrations in the blood were found along with increasing doses of selenite at the two dose-levels of mercury, on the other hand, decreased accumulation of mercury with increased doses of selenite was found in the kidneys and brain. In the liver, the largest amount of mercury was accumulated by approximate-equimolar combinations of doses. The amount of mercury transferred to the fetus was remarkably reduced in the groups injected with 12.7 mumol/kg of selenite at the two dose-levels of mercury. In the groups injected with higher dose of mercury, where fetal organs were measurable for mercury, fetal brain, liver or kidneys of the group of selenite 12.7 mumol/kg contained the least amount of mercury among the groups. All of the mice injected with 15.0 mumol/kg of mercury and 25.3 mumol/kg of selenite aborted before sacrifice.
Amnion↗