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Biomedical subjects

A Naganuma

Publications and source records attributed to A Naganuma.

At least 73 records · Page 4Linked to original sources
PubMed1988

Specific alteration of the form of selenium in fetal liver on maternal methylmercury treatment.

We have recently reported that maternal administration of methylmercury caused a striking increase in the selenium concentration in fetal liver accompanied by a decrease in selenium-dependent glutathione peroxidase (GSH-Px) activity. These changes resulted in the lowered bioavailability of selenium as far as the GSH-Px activity was concerned. The present study demonstrated that maternal administration of methylmercury caused a specific alteration of the form of selenium in fetal liver. Sephadex G-200 gel filtration of liver cytosols revealed an additional major peak of selenium in the fetal livers of mice treated with methylmercury. This peak was not present in the liver, kidney, or placenta of mothers treated with methylmercury.

Animals↗
PubMed1988

Possible role of hepatic glutathione in transport of methylmercury into mouse kidney.

The mechanism of the renal uptake of methylmercury was studied in mice. Preadministration of 1,2-dichloro-4-nitrobenzene (DCNB), which is a reagent that depletes hepatic glutathione (GSH) without affecting the renal GSH level, 30 min before injection of methylmercury significantly decreased the renal accumulation of mercury. The renal accumulation of mercury in mice receiving methylmercury-GSH intravenously was significantly higher than that in mice receiving methylmercuric chloride. These results suggest the possibility that hepatic GSH, as a source of extracellular GSH, plays an important role in the renal accumulation of methylmercury. No significant difference in renal mercury accumulation between bile duct-cannulated mice and normal mice was observed, indicating that the enterohepatic circulation of methylmercury is not an important factor in the renal accumulation of methylmercury in mice. Pretreatment of mice with acivicin, a potent inhibitor of gamma-glutamyl transpeptidase (gamma-GTP), significantly depressed the renal uptake of methylmercury and increased the urinary excretion of GSH and methylmercury. In in vitro reactions, methylmercury-GSH was degraded into methylmercury-cysteinylglycine by gamma-GTP, and this product was then converted to methylmercury-cysteine by dipeptidase. These results suggest that methylmercury is transported into the kidney as a complex with GSH, and then incorporated into the renal cells after degradation of the GSH moiety by gamma-GTP and dipeptidase, although the methylmercury bound to extracellular GSH can be reversibly transferred to plasma proteins in the bloodstream.

Animals↗
PubMed1988

Metallothionein induction prevents toxic side effects of cisplatin and adriamycin used in combination.

The protective effects of metallothionein (MT) preinduction by bismuth subnitrate (BSN) against the renal toxicity of cis-diamminedichloroplatinum (cis-DDP), the cardiotoxicity of adriamycin (ADR), and the lethal and bone marrow toxicities of these drugs were observed in mice receiving cis-DDP and ADR simultaneously. Preinduction of MT biosynthesis by BSN, which is currently used as an antidiarrheal drug, did not affect the antitumor activities of the two drugs, suggesting that the beneficial effects of the preinduction of MT biosynthesis by BSN may be applicable for therapy involving cis-DDP and ADR, either alone or in combination.

Adenocarcinoma↗
PubMed1988

Methods of removing external metal contamination from hair samples for environmental monitoring.

Human exposure to trace elements has become a major environmental issue with the growing industrialization and urbanization around the world. Hair samples are the most conveniently obtainable biopsy material and they have been identified as good indicators of the metal pollution in an environment. For their effective use, however, it is necessary to exclude the effect of external contamination of the hair surface by metals. The present investigation compares the different methods of washing hair samples prior to further treatment for elemental analysis. Deionized water, solvents (acetone, ether and carbon tetrachloride), non-ionic detergent, ionic detergent (sodium lauryl sulfate), chelating agent (EDTA-2Na), ultrasonics and combinations of these agents were used in the experiments. EDTA was found to be the most suitable of these washing agents for removing external contaminant metals. Further elucidation, however, is needed before a standard method of hair washing can be established.

Copper↗
PubMed1988

A study of the sources of external metal contamination of hair.

Sources of external metal contamination of hair were examined experimentally by exposing hair samples to soil, hot water from a water boiler for domestic use and household dust and fumes in a kitchen. Copper concentration in the hair increased markedly only when the hair was exposed to hot water from the boiler. Iron concentration in the hair increased markedly after exposure to wet soil, and increased slightly after exposure to hot water from the boiler. There was a slight decrease in zinc in the hair after exposure to wet or moist soil, and a significant increase after exposure to hot water from the boiler. When the hair was exposed to household dust and fumes, zinc showed a slight increase but copper and iron showed no change at all. The experiments with soil demonstrated the importance of water in the movement of iron from soil to hair and the role played in this process by biological factors such as soil bacteria.

Adolescent↗
PubMed1988

Effect of maternal selenium deficiency on the teratogenicity of methylmercury.

The teratogenicity of methylmercury was examined in selenium-deficient and selenium-sufficient mice of the ICR strain. A single oral dose of 75 mumol/kg of methylmercuric chloride (MMC) on day 10, 11 or 12 of gestation caused similar incidences of a cleft palate in the selenium-deficient and selenium-sufficient mice. The treatment on day 11 led to the highest incidence of a cleft palate in both groups. These results suggest that a maternal selenium deficiency has no effect on the incidence or on the critical gestational period for an MMC-induced cleft palate.

Animals↗
PubMed1988

Specific reduction of toxic side effects of adriamycin by induction of metallothionein in mice.

The effect of preinduction of metallothionein (MT) by bismuth (Bi) compounds on the toxic side effects and antitumor activity of adriamycin (ADR) was investigated in mice. Preinduction of MT by oral administration of bismuth subnitrate (BSN) significantly decreased the lethal toxicity, cardiotoxicity and bone marrow toxicity observed with a single subcutaneous injection of ADR. A significant increase in the concentration of cardiac MT was observed in mice treated with BSN. The MT level in the heart was significantly correlated with the protective effect of BSN against the cardiotoxicity of ADR. In tumor-bearing mice, pretreatment with BSN did not affect the antitumor activity of ADR, although its cardiotoxicity was significantly depressed. The ability of BSN to reduce specifically the toxicity of ADR may be ascribed to the fact that Bi induces MT in the target tissue of ADR toxicity but not in a tumor. The protective effect of MT against the toxicity of ADR, which is believed to act as an anticancer agent by generating active oxygen, can be assumed to be due to its ability to scavenge free radicals or inhibit their formation.

Animals↗
PubMed1988

Methylmercury-cysteinylglycine constitutes the main form of methylmercury in rat bile.

The chemical form of methylmercury (MM) in bile was studied by gel filtration and ion exchange chromatography using male rats of various ages. EDTA was added to all mixtures used throughout the experimental procedures in order to prevent oxidation of non-protein sulfhydryl compounds (NPSHs). MM-cysteinylglycine (CysGly) was found to be a predominant chemical form of MM in bile of 4 to 22-week-old rat exposed to methylmercuric chloride. The ratio of MM-glutathione (GSH) tended to increase with age after 4 weeks until 12 weeks of age, reflecting the age-dependent increase in the ratio of GSH to total NPSHs in bile. In 8-week-old rats, although the biliary concentration of GSH was about three times higher than that of CysGly, MM-CysGly was still one of the main chemical forms of MM in bile. This suggests that CysGly has a higher affinity for MM than GSH. In fact, when MM was mixed in vitro with GSH and CysGly in the same molar ratio as that in the bile of 8-week-old rat, MM-CysGly was found to be a predominant mercury-thiol complex. Thus, age-dependent changes in the molar ratio of biliary NPSHs together with their affinity to MM seems to determine the biliary chemical form of MM administered or added into the bile in vitro.

Animals↗
PubMed1988

Species differences in biliary excretion of methylmercury--role of non-protein sulfhydryls in bile.

Species differences in biliary excretion of methylmercury and non-protein sulfhydryls (NPSHs) were studied using male rats, mice, rabbits, guinea pigs and hamsters. EDTA was added to all mixtures used throughout the experimental procedures to prevent oxidation of NPSHs. The rates of mercury excretion into the bile of guinea pigs and rabbits after the administration of methylmercury were significantly lower than those in rats, mice and hamsters. Total NPSH concentrations in the bile of guinea pigs and rabbits analyzed by HPLC were also relatively low compared with those in the other species. These results suggested that NPSH excretion plays an important role in species differences of methylmercury excretion into bile. The chemical form of the methylmercury in the bile was analyzed by gel filtration with Sephadex G-15, and most of methylmercury in bile of all species used in the experiment was bound to low molecular weight substances. The main form of methylmercury in the bile was methylmercury-glutathione (MM-GSH) in mice and hamsters and methylmercury-cysteinylglycine (MM-CysGly) in guinea pigs. Methylmercury in the bile of mice, hamsters and guinea pigs was associated with the main component of NPSHs in bile of the respective species. In the rat bile, however, GSH accounted for a majority (80%) of NPSHs, but methylmercury was separated in two peaks on gel filtration, i.e. MM-CysGly (70%) and MM-GSH (30%). This may be explained by the higher affinity of CysGly to methylmercury than that of GSH. Our data indicate that species differences in the chemical forms of biliary methylmercury reflect the species differences in NPSH components in the bile.

Animals↗
PubMed1987

Prevention of lethal and renal toxicity of cis-diamminedichloroplatinum(II) by induction of metallothionein synthesis without compromising its antitumor activity in mice.

The participation of renal metallothionein (MT) in the toxicity and antitumor activity of cis-diamminedichloroplatinum(II) (cis-DDP) in male mice was examined. Preinduction of MT in the kidney by the s.c. administration of bismuth compounds decreased the lethality and renal and gastrointestinal toxicity caused by a single s.c. injection of cis-DDP. In the present study a correlation between the protective effect of pretreatment with bismuth nitrate against cis-DDP toxicity and the preinduced MT levels in the kidney was observed. Bismuth nitrate pretreatment showed no effect on the antitumor activity of cis-DDP against several transplantable tumors, probably because it induces MT in the kidney but not in tumor tissues. The fact that p.o. preadministration of bismuth subnitrate, an antidiarrheal drug, also depressed the lethal toxicity of cis-DDP is promising for its prompt application in medical attention. Thus, bismuth pretreatment allows higher doses of cis-DDP with no apparent toxicity, resulting in more efficient utilization of this anticancer drug.

Animals↗
PubMed1987

Induction of renal metallothionein allows increasing dose of an extensively used antitumor drug, cis-diamminedichloroplatinum.

The effect of preadministration of bismuth, a specific potent inducer of renal metallothionein (MT), on the lethal and renal toxicity of cis-DDP, an extensively used antitumor drug containing heavy metal platinum, in mice was investigated. Pretreatment of mice with two s.c. doses of bismuth nitrate (BN; 30 mumol/kg/day) at 24-hr interval prevented the lethal toxicity, the increase in BUN value and the occurrence of diarrhea caused by cis-DDP (35 mumol/kg, s.c.). This protective effect of BN-pretreatment was significantly correlated with increased MT levels in the kidney. The pretreatment of tumor-bearing mice with BN also depressed the lethal and renal toxicity of cis-DDP without compromising its antitumor activity, and allowed the administration of relatively high dose of cis-DDP. Daily five consecutive p.o. preadministration of bismuth subnitrate (BSN), one of the bismuth compounds being in use as a protectant of the gastrointestinal lining, was also effective to depress the lethal toxicity of cis-DDP. Since the effective dose of BSN is not far from that commonly used for men, this treatment will allow the increase in cis-DDP dose, promising a clinical advantage in cancer chemotherapy.

Adenocarcinoma↗
PubMed1987

Maternal selenium deficiency enhances the fetolethal toxicity of methyl mercury.

The effect of maternal selenium deficiency on methyl mercury fetotoxicity was examined in the ICR strain of mice. Pregnant mice were fed either selenium-deficient diets based on torula yeast or selenium-supplemented diets which were identical to the former except that 0.1, 0.2, or 0.4 mg of selenium per kilogram of diet was added as sodium selenite. Fetolethality of methyl mercury was exacerbated by maternal selenium deficiency when mothers were administered sc 15, 25, or 35 mumol/kg/day of methylmercuric chloride (MMC) on the 13, 14, and 15th days of pregnancy. One-tenth part per million of selenium in the diet was sufficient to protect the fetuses against MMC fetolethality when dams were administered 25 mumol/kg/day of MMC. Mercury concentrations in maternal and fetal tissues were independent of the dietary selenium level. Selenium concentration and glutathione peroxidase (GSH-Px) activity in maternal tissues were unaffected by MMC administration. In fetal liver, on the other hand, selenium concentration was increased and GSH-Px activity was decreased concurrently by maternal MMC administration in the selenium-supplemented groups. Therefore, as far as GSH-Px activity was concerned, the bioavailability of selenium was markedly decreased in fetal liver by maternal injection of MMC. The increase in selenium content in fetal liver, which was observed only in the selenium-supplemented groups, may play an important role in protection against fetolethal toxicity of MMC.

Animals↗
PubMed1987

Deficiency of selenium intake enhances manifestation of renal toxicity of cis-diamminedichloroplatinum in mice.

The effect of the dietary level of selenium on lethal and renal toxicity of cis-diamminedichloroplatinum (cis-DDP) was investigated using mice fed diets containing 4 different concentrations of selenium (0.009, 0.1, 0.4 or 1.0 ppm) for 6 weeks starting at 4 weeks of age. The groups of mice fed the diets containing 0.009 and 0.1 ppm of selenium showed higher sensitivity to the lethal toxicity caused by a single subcutaneous administration of cis-DDP (32 mumol/kg) than the other groups. The renal toxicity of cis-DDP, indicated by increases in blood urea nitrogen (BUN), serum creatinine and urinary activity of N-acetylglucosaminidase (NAG), was significantly enhanced by a decrease in dietary selenium level. These results suggest that the dietary level of selenium affects the manifestation of lethal and renal toxicity of cis-DDP.

Acetylglucosaminidase↗
PubMed1985

A simple and rapid method for preparation of 203Hg-labeled methylmercury from 203HgCl2 and methylcobalamin.

A rapid and simple method for preparation of 203Hg-labeled methylmercuric chloride (CH3(203)HgCl) from 203HgCl2 and methylcobalamin is described. More than 99% of 203Hg was methylated with methylcobalaminin 0.01 N HCl during 1 h. CH3(203)HgCl formed during the reaction was rapidly and completely separated from cobalamins and unreacted 203HgCl2 by CM-Sephadex C-25 minicolumn. The low cost procedure for preparation of CH3(203)HgCl can be completed within 2 h and yields an inorganic 203Hg-free CH3(203)HgCl which is useful in methylmercury toxicology.

Isotope Labeling↗