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Biomedical subjects

L Dencker

Publications and source records attributed to L Dencker.

At least 73 records · Page 4Linked to original sources
PubMed1984

Placental transfer and fetal distribution of lead in mice after treatment with dithiocarbamates.

The distribution of i.v. administered lead (203Pb-acetate; 50 nmol/kg b.w.) was studied by means of autoradiography and impulse counting in pregnant C57BL mice (day 18) treated orally with dithiocarbamates. Diethyldithiocarbamate ( DEDTC ), disulfiram or thiram (2 X 1 mmol/kg b.w.) or vehicle ( gelatine ) alone, was given by gavage 2 h before and immediately after the injection of lead. All three dithiocarbamates, especially thiram, changed the distribution pattern of lead. Thiram and DEDTC had the greatest effect at 4 h after lead administration, disulfiram at 24 h. In the mother, most notably the brain concentration increased (70-fold for thiram at 4 h) while that of erythrocytes and skeleton decreased (50- and 4-fold, respectively). The total fetal concentration unexpectedly showed only a moderate increase (approximately 2-fold for thiram), which may be due partly to the low maternal plasma lead concentration. The partition within the fetal tissues was, however, changed by the dithiocarbamates in much the same way as in the mothers, e.g., the fetal brain of thiram treated animals had increased by a factor 15, while skeletal and blood concentrations were lowered compared to controls. In melanin containing structures of the maternal and fetal eyes a dramatic increase in lead concentration resulted from dithiocarbamate treatment (lead ions are known to bind to melanin in vitro). The pattern of changes in lead distribution caused by dithiocarbamates is consistent with the formation in the body of lipid soluble lead-dithiocarbamate complexes that pass biological barriers more easily than lead inorganic (to brain, fetus, melanocytes etc.), probably followed by a dissociation of the complexes in the tissues.

Animals↗
PubMed1984

Interactions between tellurium and mercury in murine lung and other organs after metallic mercury inhalation: a comparison with selenium.

Selenium is known to form complexes with heavy metals in the blood and thus increase the retention time of the metals in several organs, especially in the reticulo-endothelial system. Selenium may similarly cause retention of mercury in the lung after metallic mercury (Hg0) inhalation. This study, comparing the effects of tellurium with those of selenium (both in group '6b' of the periodical system), showed that Te(IV) was as effective as Se(IV) and Se(VI) (all given in a dose of 10 mumol/kg body wt.) in retaining inhaled 203Hg0 (1.5 mumol/kg body wt.) in the lung (presumably 203Hg2+ after oxidation). Te(VI) had to be given in a dose of 100 mumol/kg body wt to produce the same effect. As in the lung, also in other organs tellurium caused a dose-dependent increase in mercury retention. At a dose level of 10 mumol Te(IV) per kg body wt. the mercury retention ratios (treated/control) were 140 for the lung and 8.6 for the whole body. The corresponding figures for Te(VI) (10, 30 and 100 mumol/kg body wt.) were 10, 73 and 120 and 3.7, 3.9 and 4.3, respectively. Retention of i.v. injected 203HgCl2 was increased by pre-administration of tellurium, again in a dose-dependent manner and Te(IV) being 3-10 times more effective than Te(VI). The kidney and the spleen were the dominant organs, as is the case after Se pretreatment. Anions of other elements, arsenite, arsenate, chromate, molybdate and wolframate (30 mumol/kg body wt.), did not affect the retention of 203Hg in lung or any other organ, or in the whole body after inhalation of 203Hg0. It is suggested that Te(IV) may easily be reduced to Te2- (in analogy with selenium) which may complex with Hg2+. The liability for Te(VI) to be reduced to Te2- appears to be approx. 10 times lower.

Administration, Intranasal↗
PubMed1984

Teratogenicity of 2,3,7,8-tetrachlorodibenzofuran in BXD recombinant inbred strains.

A series of recombinant inbred strains called BXD [produced from a cross between C57BL/6J (B6) and DBA/2J (D2)] were given single i.p. doses of 0.6 mg/kg 2,3,7, 8-tetrachlorodibenzofuran (TCDBF) on day 12 of gestation. The uteri were examined in late gestation with respect to resorptions and fetal death, and fetal malformations. The strains of the B6-type with respect to Ah-locus (Nos. 5, 6, 8, 11, 12, 14, 16 and 29) that are Ah-responsive, exhibited cleft palates in 80-100% of all fetuses, while hydronephrosis occurred at a rate of 20-70%. These two types of malformation are well recognized from earlier experiments with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and its structural analogues, including TCDBF. In the strains of D2-type with respect to Ah-locus (Nos. 2, 15, 19, 21, 22, 24, and 31), which are Ah-nonresponsive, no cleft palates occurred. One strain (No. 2) had a few (17%) fetuses with hydronephrosis. The frequency of fetal deaths and resorptions were relatively low, but slightly higher among B6-strains than D2-strains. The results indicate an association between the genes producing malformations by TCDBF and the Ah-locus.

Abnormalities, Drug-Induced↗
PubMed1984

Teratogenicity of TCDD and the congener 3,3',4,4'-tetrachloroazoxybenzene in sensitive and nonsensitive mouse strains after reciprocal blastocyst transfer.

The teratogenic sensitivity to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and its congeners is straindependent in the mouse. Reciprocal blastocyst transfer was performed between sensitive (NMRI) and nonsensitive (DBA) strains to show if there is a direct effect on embryonic tissues or if damage is secondary to maternal effects. Treatment with TCDD (30 micrograms/kg body weight) and 3,3',4,4'-tetrachloroazoxy-benzene (TCAOB)(8 mg/kg) on day 12 caused cleft palate in 75-100% of all NMRI fetuses, irrespective of whether they had remained in their own (NMRI) dams or as aliens in DBA dams. Only 1 out of 25 alien NMRI fetuses in DBA dams did not develop cleft palate. Under the same conditions, none of the 24 DBA fetuses in NMRI dams had cleft palate, although 89% of their NMRI littermates were affected. Also, no DBA fetuses having developed in their own dams had cleft palate.

Animals↗
PubMed1984

Teratogenicity of 2,3,7,8-tetrachlorodibenzofuran in the mouse.

2,3,7,8-Tetrachlorodibenzofuran (TCDBF) was administered in single doses (0.1-0.8 mg/kg body weight) intraperitoneally to pregnant C57BL mice on d 10, 11, 12, or 13 of gestation. A dose-dependent increase was observed in the frequency of fetal resorptions and fetal death, especially in the earlier stages (d 10-11). Cleft palate and hydronephrosis as well appeared in a dose-dependent manner, with a peak in sensitivity after administration on d 11-12. TCDBF given at a dose level of 0.1 mg/kg body weight on d 12 of gestation (only dose- and stage-tested) produced a marked thymic hypoplasia as well. A few cases of general hydrops occurred. The pattern of malformations and time of sensitivity corresponded well to that observed earlier after administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; ED50 approximately equal to 25 micrograms/kg) and 3,3',4,4'-tetrachloroazoxybenzene (TCAOB; ED50 approximately equal to 6 mg/kg), two congeners of TCDBF, indicating common mechanisms of action of this family of compounds. Ornithine decarboxylase (ODC) is an important enzyme in cell proliferation and growth with a high activity in embryonic tissues. Liver ODC activity has previously been found to be stimulated by TCDD in weaning mice. However, this enzyme was not found to be stimulated in fetal and placental tissues, but slightly in maternal kidney after treatment with TCDBF in teratogenic doses. It is possible that the ODC activity increases under certain conditions only, on administration of TCDD and its congeners.

Abnormalities, Drug-Induced↗
PubMed1984

Embryotoxicity of arsenite and arsenate: distribution in pregnant mice and monkeys and effects on embryonic cells in vitro.

The distribution of 74As-labelled arsenate and arsenite in pregnant mice and a monkey has been studied by autoradiography and gamma counting of isolated tissues, and their in vitro toxicity to a chondrogenic system has been investigated. With both arsenic forms, given as single intravenous injections to the mother, the 74As-arsenic appeared to pass the mouse placenta relatively free and approximately to the same extent. The retention time in maternal tissues including the placenta was, however, around three times longer with arsenite than with arsenate. In early gestation, high activity was registered in the embryonic neuroepithelium, which correlates well with reported CNS malformations in rodents. In late gestation, the distribution pattern was more like that in the adults. Accumulation in skin and squamous epithelia of the upper gastrointestinal tract (oral cavity, oesophagus and oesophageal region of stomach) dominated the distribution picture, especially at a long survival interval. Arsenate, but not arsenite, showed affinity for the calcified areas of the skeleton. A marmoset monkey in late gestation receiving arsenite showed a somewhat lower rate of placental transfer than the mice. Skin and liver had the highest concentrations (at 8 hrs), both in mother and foetuses. This species is known not to methylate arsenic, resulting in stronger binding and longer retention times of arsenic as compared with other species. The stronger binding in maternal tissues may possibly explain the lower rate of placental transfer. Arsenite was shown to inhibit cartilage formation in a chick limb bud mesenchymal spot culture system (ED50 approximately 5-10 microM), while arsenate seemed to be without effect at concentrations up to 200 microM (highest tested). Arsenate, however, showed a potentiation of the arsenite toxicity.

Animals↗
PubMed1984

Organ and cellular distribution of inhaled metallic mercury in the rat and Marmoset monkey (Callithrix jacchus): influence of ethyl alcohol pretreatment.

Distribution of inhaled radioactive metallic mercury vapour (203Hg0) in rats and Marmoset monkeys (Callithrix jacchus), with or without pretreatment by ethyl alcohol or aminotriazole (rat), was studied by means of whole-body autoradiography, microautoradiography and scintillation counting of excised organs. Metallic mercury is oxidized by the catalase-H2O2 complex (Complex I) to the ionic form (Hg2+) and is known to be accumulated and retained in organs such as lungs, liver, myocardium, and brain, apparently after local oxidation in these organs. To this list of organs can be added the whole respiratory tract (nasal mucosa, trachea, and bronchi), a number of endocrine organs such as adrenal cortex, thyroid, corpora lutea of the ovaries, and interstitial tissues of the testes, the uvea and retina of the eye, and the salivary glands. In the liver, a regionalized pattern of distribution corresponding to the periportal hepatocytes was observed. Similarly, the subcapsular parts of the adrenal cortex (mainly the zona glomerulosa) were responsible for most of the adrenal mercury oxidation and retention. These organs (liver, adrenal) thus have a reserve capacity to oxidize Hg0. This is apparent also by the fact that ethyl alcohol and aminotriazole (known catalase inhibitors)--which depress oxidation and retention in most organs and whole body and thus increase blood concentrations of Hg0--cause an increased retention in most liver and adrenal cells.

Amitrole↗
PubMed1984

Accumulation in murine amniotic fluid of halothane and its metabolites.

The distribution of radioactivity in pregnant mice was registered at 0, 4, and 24 hrs after a 10 min. period of inhalation of 14C-halothane. Autoradiographic methods were used to allow to distinguish between the distribution of volatile (non-metabolize) halothane, water-soluble metabolites, and firmly tissue-bound metabolites. While volatile radioactivity was seen predominantly at short survival intervals, e.g. in body fat, blood, brain and liver, metabolites accumulated with time. Peak values occurred at 4 hrs in most organs (measured with liquid scintillation as well). The most remarkable findings were the high concentrations of radioactivity in amniotic fluid (and the ocular fluids of adults) with peak values at 4 hrs and rather high concentrations still prevailing at 24 hrs after inhalation. It is assumed that this activity represents only partly volaile halothane and mostly non-volatile metabolites. High activity of metabolites was seen in the neuroepithelium of the embryo in early gestation. Firmly tissue-bound metabolites, still remaining after washing the tissues with trichloroacetic acid and organic solvents, were found in the nasal mucosa, trachea and bronchial tree and in (presumably centrilobular) zones of the liver of adults after inhalation and 5-day old mice after intraperitoneal injection, indicating the formation of reactive metabolites in these organs. Firmly tissue-bound activity was not observed in the corresponding foetal organs.

Amniotic Fluid↗
PubMed1984

Lack of effect of indomethacin on mesenchymal limb-bud cells in vitro.

Stimulated by reports of an inhibitory effect of non-steroid anti-inflammatory drugs on fracture healing and heterotopic bone formation in clinical and experimental studies, this investigation was performed to study the effect of indomethacin on chondrogenesis and mineralization in vitro by chicken mesenchymal limb-bud cells. Limb-bud cell cultures were treated with indomethacin and, in order to study a possible effect of metabolites, with serum from indomethacin-treated rats. No effects of the drug on chondrogenesis, as estimated by staining with alcian blue, could be detected. This was also the case when mineralization in the cultures induced by high phosphate concentrations was studied. It is concluded that indomethacin probably exerts its effect on bone metabolism through mechanisms other than modulation of cell differentiation or cell proliferation.

Animals↗
PubMed1984

Fetotoxicity of inorganic mercury in the mouse: distribution and effects on nutrient uptake by placenta and fetus.

Different aspects on the fetotoxicity of HgCl2 have been studied in vivo and in vitro and have been compared to earlier results with CdCl2, which is known to cause placental necrosis and fetal death. Hg has to be given in higher doses (20-25 mg/kg body weight) than Cd (3-4 mg/kg body weight) to cause fetolethality in late pregnancy in the mouse. It does not cause the typical signs of placental damage (congestion and bleedings) as does Cd. At a dose level of 15 mg/kg body weight, Hg reaches more than 10 times higher concentrations (approx. 5 times higher on a molar basis) in the fetus, while Cd (4 mg/kg body weight) on the other hand appears in the placenta at a double molar concentration as compared to Hg. In a chick, limb bud mesenchyme cell culture differentiating into chondrocytes, Hg and Cd were about equally effective in inhibiting cartilage-specific staining by alcian blue (ED50 approximately 1 microM). Due to the strong accumulation of Hg and Cd in the placenta, the effects of Hg on the placental and fetal uptake of four nutrients was studied. Hg caused a dose-dependent decrease in fetal radioactivity as compared to controls 4 hours after administration of 57Co-vitamin B12 to the mother. However, this effect was not as marked as for Cd. Hg, on the other hand, decreased fetal radioactivity after 14C-alpha-aminobutyric acid more than Cd did. Both elements decreased the fetal uptake of 65Zn, probably due mainly to a concomitant decrease in maternal serum concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminobutyrates↗
PubMed1984

Effects of cadmium on the placental uptake and transport to the fetus of nutrients.

Cadmium (Cd) is known to produce malformations, growth inhibition of the fetus, and placental necrosis in rodents at higher doses (3-4 mg/kg body wt). We studied the influence of Cd in various doses (0.5-4 mg/kg body wt) and at different survival intervals on the placental uptake and transfer to the fetus of vitamin B12 (vit. B12), zinc (Zn), alpha-aminobutyric acid (AIB), and deoxyglucose (DOX). These were chosen to represent various mechanisms of membrane transport. We show that vit. B12, which is accumulated in the placenta by a presumed receptor-mediated mechanism, is most easily disturbed by Cd. Thus, a significant decrease in transfer to the fetus was seen already 1 h after a high dose (4 mg/kg body wt) of Cd, and also at longer intervals (24 h) after low doses (0.5 mg/kg body wt). The transport of Zn (chemically similar to Cd) was also disturbed, but its inhibition was probably due in part to a decreased maternal serum concentration. The transport of AIB and DOX was largely unaffected. We conclude that inhibition of nutrient transfer to the fetus may be the underlying mechanism of growth retardation and possibly of the malformations produced by Cd. Vitamin B12 may be a sensitive indicator of early and subtle disturbances of placental function, not only for Cd but also for other chemicals suspected of causing placental disturbances.

Aminobutyrates↗
PubMed1983

Interactions between selenium and mercury in mice: marked retention in the lung after inhalation of metallic mercury.

The distribution of 203Hg after inhalation of radioactive metallic mercury (4.3 mumol 203Hg0/kg body wt. for 1 h) was studied in saline (control) and selenite (10 mumol/kg body wt. intraperitoneally, i.p.) pretreated male C57BL mice by means of whole-body autoradiography and scintillation counting. Selenite pretreatment did not apparently change the immediate uptake and distribution of 203Hg (presumably inorganic Hg after oxidation in the different organs) but markedly increased the retention time in the whole body. The most marked retention was seen in the lungs where the selenite-pretreated animals had 200 times higher concentration as compared to control animals 14 days after inhalation. In other organs the corresponding value ranged between 1 (brain) and 12 (spleen). Selenite-pretreated and control animals showed the same low rate of exhalation of 203Hg after the inhalation period, while the latter animals eliminated significantly more through the urine and faeces (measured only during the first 24 h). When inversely radioactive selenite (75Se-selenite) was injected i.v. into animals 1 h earlier exposed to non-radioactive Hg0 (by inhalation), the lung concentration of 75Se after 24 h was 4 times higher than that of control animals. When radioactive mercury was injected i.v. in the form of 203HgCl2 (4.3 mumol/kg body wt.), selenite (10 mumol/kg body wt., i.p.) increased the retention time in the body, more so than after 203Hg0 inhalation. In this case the mercury was retained especially in the serum, red pulp of the spleen and liver (reticulo-endothelial system). 75Se-selenite injected i.v. after i.p. administration of non-radioactive HgCl2 in the same doses as above similarly accumulated more in serum, spleen and liver as compared to control animals. It is presumed that while injected selenite and inorganic mercury (Hg2+) interact strongly in the serum, increasing each other's uptake and retention especially in the reticulo-endothelial system, inorganic mercury retained in various organs after oxidation of Hg0 upon inhalation interacts with selenium mainly intracellularly. This occurs especially in the lungs, where initially high concentrations of mercury are found after inhalation.

Animals↗
PubMed1983

Whole body and liver distribution of inhaled mercury vapor in the mouse: influence of ethanol and aminotriazole pretreatment.

Inhalation of radioactive metallic mercury vapor (203Hg0) in the mouse resulted in an accumulation of mercury in several organs where no specific uptake was observed after i.v. injection of inorganic mercury (203Hg2+). This was true for the whole respiratory epithelium (including the lung parenchyma), myocardium, brain, retina of the eye, adrenal cortex, corpora lutea of the ovary, epididymis, brown fat and thyroid gland. It is assumed that these organs have a high capacity for oxidizing Hg0 to Hg2+, which will then be retained in the tissues. Ethanol and aminotriazole (catalase inhibitors) decreased the concentration in several of these organs, although not in an exactly similar pattern. In the livers of non-treated animals, most of the inhaled mercury accumulated in the hepatocytes in the periphery of the lobuli (periportal region), close to where the blood vessels enter the liver parenchyma. Treatment with ethanol or aminotriazole increased the liver mercury content, with more or less all the hepatocytes apparently engaged in the oxidation of Hg0.

Amitrole↗
PubMed1983

Transplacental movement of inorganic lead in early and late gestation in the mouse.

203Pb(NO3)2 was administered i.v. to pregnant C57BL mice at different stages, from day 8 to day 18 of gestation. The whole animals or excised uteri were subjected to autoradiography or were autopsied for scintillation counting of excised organs. Lead appeared in embryonic and fetal tissues at all stages of gestation. Early (approx. day 8-11) lead was restricted mainly to the embryonic blood, suggesting that free lead was essentially not transferred to the embryo but may have been incorporated in the embryonic hemoglobin when the erythrocytes were formed in the yolk sac placenta (an extraembryonic membrane). From day 12 and later, an uptake was seen in the liver and the cartilaginous skeleton, and from day 14, a strong accumulation was found in calcified bone. This means that the overall fetal concentration increased successively with gestational age of the conceptus. The uptake in fetal liver may be related to the erythropoiesis taking place in the liver in later gestation. While an accumulation of lead was observed in proximal tubuli of the maternal kidney, no corresponding uptake occurred in the fetal kidney. Although lead is teratogenic, causing among others skeletal defects, no effect of inorganic lead in mM concentration was seen on a chondrogenic cell system in vitro. Due to the predominance of lead in hemoglobin, a mechanism of teratogensis based on inhibition of fetal hemoglobin synthesis or function is discussed.

Animals↗
PubMed1983

Metabolism of arsenobetaine in mice, rats and rabbits.

The distribution, retention and biotransformation of arsenobetaine, the most common organic arsenic compound in fish and crustacea, have been studied in mice, rats and rabbits by use of synthesized 73As-labelled arsenobetaine. Orally administered arsenobetaine was almost completely absorbed from the gastro-intestinal tract in mice. The urinary excretion for 3 days following intravenous injection was about 75% of the dose in the rabbits and more than 98% in the mice and rats. The rate of excretion in mice was independent of the dose level in the range 4 to 400 mg As/kg body weight. In both animal species the tissue distribution differed widely from that observed following exposure to inorganic arsenic. The clearance of arsenobetaine from plasma and most tissues was fast (somewhat faster in mice than in rabbits) and seemed to follow first-order kinetics. The clearance from cartilage, testes, epididymis, and in the rabbits also the muscles, was slower and consisted of more than one phase. 73As-arsenobetaine was the only labelled arsenic compound detected in urine and soluble extract of tissues, indicating that no biotransformation occurred.

Animals↗
PubMed1983

Placental transfer of hexachlorophene (HCP) in the marmoset monkey (Callithrix jacchus).

Autoradiography was used to study the distribution of 2,2'-14C-methylene-bis-(3,4,6-trichlorophenol) (HCP) in pregnant marmoset monkeys in early (day 30-50) and late (around day 120) gestation and in a newborn (11 days old) pup. Radioactivity was present in the conceptus at all stages of gestation, although the foetal concentration was lower than the maternal. In the embryo an accumulation was observed in the neural tube and in the embryonic membranes. In the late foetus and newborn monkey the highest concentration of radioactivity was found in the liver and the intestinal contents. The brain of the adult and newborn animals showed low concentration. A partial blood-brain barrier was present in the late foetus but, in relation to other tissues, the foetal brain concentration was higher than that of the mother.

Animals↗