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1. |
Effects of Dithiocarbamates on Intestinal Absorption and Organ Distribution of Cadmium Chloride in Mice |
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Pharmacology&Toxicology,
Volume 64,
Issue 3,
1989,
Page 239-243
Ole Andersen,
Jesper B. Nielsen,
Mark M. Jones,
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摘要:
Abstract:Earlier publications have demonstrated that diethyldithiocarbamate (DDC) antagonizes the acute toxicity of injected CdCl2but enhances the acute toxicity of orally administered CdCl2, most likely due to the high lipophilicity of DDC and the complex formed with the Cd++ion. This study demonstrates that the hydrophilic dithiocarbamates dihydroxyethyldithiocarbamate (DHE‐DTC) and N‐methyl‐N‐glucamyl dithiocarbamate (NMG‐DTC) also enhance the intestinal absorption of orally administered CdCl2in mice, although less efficiently than DDC. After oral as well as intraperitoneal administration 15 min. after a single oral dose of CdCl2the dithiocarbamates tested enhanced the intestinal cadmium uptake with a relative efficiency, DDC>DHE‐DTC>NMG‐DTC, which correlated to the lipophilicity of both the dithiocarbamates and the complexes formed with the Cd++ion. Intraperitoneal administration of DDC induced extensive changes in the relative organ distribution of absorbed cadmium, compared to the distribution of CdCl2administered alone. However, the only noticeable effect of administration of DHE‐DTC and NMG‐DTC was decreased gastrointestinal deposition of cadmium, irrespective of the administration route of the dithiocarbamates. Earlier studies have demonstrated that DDC and various other dithiocarbamates are capable of mobilizing intracellular cadmium deposits, presumably due to some lipophilicity. This study demonstrates that these dithiocarbamates may also enhance the intestinal abso
ISSN:0901-9928
DOI:10.1111/j.1600-0773.1989.tb00638.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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2. |
Effect of Short‐Term Ammonia Inhalation on Selected Amino Acids in Rat Brain |
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Pharmacology&Toxicology,
Volume 64,
Issue 3,
1989,
Page 244-246
Alli T. A. Manninen,
H. Savolainen,
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摘要:
Abstract:Increased brain and plasma glutamine after ammonia inhalation had an effect on the concentrations of selected amino acids in rats. Rats inhaled ammonia vapour of 25 and 300 p.p.m. for 5 days 6 hr daily. Brain glutamine increased from the control level, 10.9±2.6 (S.D.) μmol/g to 15.5±5.2 (S.D.) μmol/g (P<0.05) in 25 p.p.m. NH3and to 15.3±1.1 (S.D.) μmol/g (P<0.01) in 300 p.p.m. NH3. The blood glutamine was also increased so that the brain/plasma ratio was not changed. A slight elevation in the brain threonine was found, from 0.6±0.1 (S.D.) μmol/g (controls) to 0.8±0.2 (S.D.) μmol/g in 25 p.p.m. and to 0.8±0.1 (S.D.) μmol/g in 300 p.p.m. NH3. The brain/plasma ratio of threonine was increased at the 300 p.p.m. level. The increasing brain threonine linearly correlated to the increased plasma glutamine the general correlation co‐efficient being 0.59 according to a linear regression analysis. The effects on other amino acids, e.g., glycine, alanine, serine, aspartate, glutamate, were less clear. It seems that the elevated blood glutamine impaired the threonine export or augmented its uptake from the blood stream. Exposure to NH3vapour by inhalation proved to be an alternative model to portocaval shunting or urease injections in the study of hyperammonemia
ISSN:0901-9928
DOI:10.1111/j.1600-0773.1989.tb00639.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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3. |
Treatment of Experimental Acute Uranium Poisoning by Chelating Agents |
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Pharmacology&Toxicology,
Volume 64,
Issue 3,
1989,
Page 247-251
Arturo Ortega,
José L. Domingo,
Mercedes Gómez,
Jacinto Corbella,
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摘要:
Abstract:Sixteen chelating agents were examined to determine their relative efficacy as antidotes in acute uranyl acetate intoxication in mice after subcutaneous administration. Chelators were administered intraperitoneally to male Swiss mice at a dose equal to one‐fourth of their respective LD50 and the therapeutic effectiveness was calculated. Eight compounds resulted in a significant enhancement of the survival rate: Tiron, gallic acid, DTP A, p‐aminosalicylic acid, sodium citrate, EDTA, 5‐aminosalicylic acid and EGTA. Therapeutic indices (TI) were then determined for these chelating agents. Tiron (TI: 158), gallic acid (TI: 116) and DTPA (TI: 44.9) were the most effective antidotes. In subsequent experiments, uranyl acetate dihydrate was administered subcutaneously (10 mg/kg) in a 24 hr excretion and distribution study. The previous eight chelators were given intraperitoneally ten min. after the uranium administration. 5‐Aminosalicylic acid and tiron were consistently the most effective in increasing the urinary and faecal excretion of uranium respectively. A decrease of the uranium concentration in kidneys and bone was also noted with tiron. Tiron appears to be the most effective agent of those tested in the prevention of acute uranium intox
ISSN:0901-9928
DOI:10.1111/j.1600-0773.1989.tb00640.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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4. |
Increased Thermal Stability of Collagen after 2,5‐Hexanedione Intoxication in Rats |
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Pharmacology&Toxicology,
Volume 64,
Issue 3,
1989,
Page 252-256
Hans Brændgaard,
Troels T. Andreassen,
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摘要:
Abstract:The present study examined the ability of 2,5‐hexanedione (2,5‐HD) to cross‐link the fibrillary protein, collagen,in vivo.The thermal stability of collagen measured as the isometric contraction‐relaxation force was studied in tail tendons from rats, recieving 2,5‐HD intraperitoneally for 2 or 6 weeks (1 g/kg/week, divided into 3 doses). The maximum contraction force was significantly increased after 6 weeks of intoxication as compared to controls, indicating an increase in covalent cross‐linking between collagen molecules. Likewise,in vitroincubation of rat tail tendons in 2,5‐HD for 24 hr induced an increase in thermal isometric cont
ISSN:0901-9928
DOI:10.1111/j.1600-0773.1989.tb00641.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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5. |
Extracorporeal Complexation and Haemodialysis for the Treatment of Cadmium Poisoning. I. Effects of Four Chelators on thein VitroElimination of Cadmium from Human Blood |
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Pharmacology&Toxicology,
Volume 64,
Issue 3,
1989,
Page 257-261
Fayad Z. Sheabar,
S. Yannai,
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摘要:
Abstract:The effect of ethylenediamine tetraacetic acid (EDTA), glutathione (GSH), citrate and 2, 3‐dimercaptosuccinic acid (DMSA) on the elimination of cadmium (Cd) from human blood, by complexing haemodialysis, was investigatedin vitro.A significant increase in elimination rate was observed with all four chelators compared to that observed without chelators. EDTA was found to be the most effective agent, which at a level of 0.01M in the dialysate facilitated elimination of 80% of the blood Cd originally presen
ISSN:0901-9928
DOI:10.1111/j.1600-0773.1989.tb00642.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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6. |
The Absorption and Distribution of14C‐Bacitracin in Rainbow Trout (Salmo gairdneri) after a Single Oral Dose, as Observed by Whole Body Autoradiography |
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Pharmacology&Toxicology,
Volume 64,
Issue 3,
1989,
Page 262-265
T. Høy,
T. E. Horsberg,
I. Nafstad,
G. N. Berge,
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摘要:
Abstract:This study was performed to investigate the absorption, distribution and elimination of orally given radiolabelled bacitracin methylene disalicylate (BMD) in rainbow trout kept in salt water. The level of radioactivity in skeletal muscle tissue remained low, but stable throughout the experiment, while radioactivity in bile and liver tissue increased for about 48 hr, before decreasing. There was a trapping of BMD and/or its metabolites in excretory kidney tissue, where the amount of radioactivity continued to increase when radioactive material was being removed from other tissues. The maximum concentration found in excretory kidney tissue was about 7 times as high as the maximum concentration found in the liver. Even though there is no appreciable absorption of BMD from the gastrointestinal tract in homoiotherms, we found the absorption in rainbow trout to be significant.
ISSN:0901-9928
DOI:10.1111/j.1600-0773.1989.tb00643.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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7. |
The Levels of Somatostatin in the Brain and CSF of Rat after Carbamazepine Administration |
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Pharmacology&Toxicology,
Volume 64,
Issue 3,
1989,
Page 266-271
Asia Pitkänen,
Juha‐Matti Hyttinen,
Jouni Sirviö,
Jukka Jolkkonen,
Helena Sarlund,
Paavo Riekkinen,
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摘要:
Abstract:Previous studies have suggested that carbamazepine (CBZ), a potent antiepileptic drug, affects the somatostati‐nergic system in humans and animals; but the results have been contradictory. In the present study we further evaluated the effect of CBZ administration on somatostatin‐like immunoreactivity (SLI) in cisternal cerebrospinal fluid (CSF) and in different areas of the rat brain. Somatostatin receptor binding in the cortex of CBZ‐treated rats was also studied. Two hours after administration of CBZ at a dose of 30 mg/kg intraperitoneally, which resulted in a serum CBZ concentration of 64 μM, the SLI in CSF was lower than in vehichle‐injected controls (P = 0.024, MANOVA). In the hippocampus SLI was elevated to 132% that of vehicle‐injected controls (P = 0.016, Mann‐Whitney U‐test). At a dose of 15 mg/kg a slight decrease in SLI was seen in CSF compared to vehicle‐injected controls (P = 0.034, MANOVA) but no change was observed in the hippocampus. After administration of CBZ for 7 days (30 mg/kg intraperitoneally twice a day) we were not able to demonstrate any definitive change in SLI of rat CSF (MANOVA). In these rats the SLI in the hypothalamus was elevated compared to vehicle‐injected controls (132%, P = 0.016, Mann‐Whitney U‐test). In experiments with both acute and chronic administration of CBZ, the somatostatin receptor binding was unchanged. The present study suggests that administration of CBZ only slightly affects the somatostatinergic s
ISSN:0901-9928
DOI:10.1111/j.1600-0773.1989.tb00644.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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8. |
Effect of Repeated Administration of Berenil on Urinary Enzyme Excretion with Corresponding Tissue Pattern in Rats |
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Pharmacology&Toxicology,
Volume 64,
Issue 3,
1989,
Page 272-275
Musbau A. Akanji,
Edwin O. Ngaha,
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摘要:
Abstract:The effect of repeated administration of berenil, a trypanocide, on urinary excretion of some enzyme activities in rat and their corresponding levels in the kidney and serum was investigated. Daily administration of this drug to rats resulted in increased urinary volume, excretion of protein, alkaline phosphatase and lactate dehydrogenase activities. However, the level of acid phosphatase activity was not significantly increased while muramidase activity disappeared completely during the period of drug administration. In the kidney tissue, there was a significant loss of lactate dehydrogenase activity immediately after the first dose and this trend continued until the end of drug administration. In the same tissue, there was an increase in alkaline phosphatase activity while the lysosomal enzymes were not significantly affected. In the serum, except for the increase in alkaline phosphatase activity, all other enzymes were not significantly affected. All these results indicate that there is cellular damage to rat kidney as a result of repeated berenil administration, and that the plasma membrane and the soluble portion of the cytoplasm are the primary site of injury to the cells. They also suggest that urinary enzyme excretion could be useful in determining the site of cellular damage by chemical agents in kidneys.
ISSN:0901-9928
DOI:10.1111/j.1600-0773.1989.tb00645.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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9. |
Comparison of Intra‐ and Extrasynaptosomal Monoamine Oxidase‐A and ‐B Activities in the Striatum and Frontal Cortex of Two Mice Strains with Different Sensitivities to the Neurotoxic Actions of 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine |
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Pharmacology&Toxicology,
Volume 64,
Issue 3,
1989,
Page 276-281
Anders Stenström,
Erik Sundström,
Christopher J. Fowler,
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摘要:
Abstract:Conditions for the assay of the intra‐ and extrasynaptosomal rates of deamination of dopamine and noradrenaline by the two forms of monoamine oxidase (MAO) have been determined in striatal and frontal cortical homogenates, respectively, from C57 BL/6 mice. The activities obtained were compared with the corresponding activities found for NMRI mice, a strain less sensitive to the neurotoxic effects of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) than the C57 BL/6 strain. In both strains, the intra‐ and extrasynaptosomal deamination of dopamine in the striatal homogenates was brought about predominantly by MAO‐A. No significant differences between the two strains were found for the intra‐ or extrasynaptosomal MAO‐A or ‐B activities towards dopamine in striatal homogenates. On the other hand, the striatal dopamine concentrations were higher in the C57 BL/6 mice than in the NMRI mice. The concentrations of the dopamine metabolites DOPAC and HVA were similarly higher, suggesting that the rate of turnover of dopamine is the same for the two strains. In frontal cortical homogenates, MAO‐A predominated in the deamination of noradrenaline both intra‐ and extrasynaptosomally. The extrasynaptosomal rates of deamination of noradrenaline were similar in the two mice strains, whereas the intrasynaptosomal MAO‐A activity was significantly higher for the C57 BL/6 mice. These results concur with and extend to the noradrenergic system the conclusion previously made by Jossanet al.(1987) for the dopaminergic system that although MAO‐B activity is necessary for expression of MPTP neurotoxicity, it is not the rate‐limiting step for the develo
ISSN:0901-9928
DOI:10.1111/j.1600-0773.1989.tb00646.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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10. |
Investigation of Lipid Peroxidation Induced by Hydrazine Compoundsin Vivoin the Rat |
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Pharmacology&Toxicology,
Volume 64,
Issue 3,
1989,
Page 282-285
Nicholas E. Preece,
John A. Timbrell,
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摘要:
Abstract:Phenylhydrazine caused lipid peroxidation in ratsin vivoas detected by expiration of ethane but this was not due to lipid peroxidation in liver, as there was no associated MDA production in this tissue. Hydrazine did not cause either ethane expiration or MDA formation. Both hydrazine and phenylhydrazine caused a significant increase in propane expiration. Phenylhydrazine significantly decreased packed cell volume and haemoglobin levels but hydrazine had no effect on these parameters. These data indicate that the early toxicity of hydrazine does not involve peroxidation of lipids whereas phenylhydrazine causes lipid peroxidation possibly within the erythrocyte, perhaps by interaction with red cell haemoglobin.
ISSN:0901-9928
DOI:10.1111/j.1600-0773.1989.tb00647.x
出版商:Blackwell Publishing Ltd
年代:1989
数据来源: WILEY
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