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H Tanii

Publications and source records attributed to H Tanii.

At least 55 records · Page 3Linked to original sources
PubMed1990

Effects of neurotropic agents with a selectivity for alpha-adrenoceptors on nitrile-induced dyskinetic syndrome in mice.

Allylnitrile, crotononitrile and 2-pentenenitrile induce this behavioral syndrome, which includes persistent random circling, head twitching and backward running. The effects of neurotropic agents, with a selectivity for the alpha 1 or alpha 2 adrenoceptor, were examined on the nitrile-induced behavioral abnormalities. The alpha 1 agonist phenylephrine, the alpha 2 agonist clonidine and the alpha 1 antagonist prazosin, inhibited the behavioral syndrome induced by each nitrile, while the alpha 2 antagonist yohimbine had no effect. These results suggest that the noradrenergic system may be involved in the manifestation of the syndrome. Furthermore, a tonic noradrenergic influence on subcortical systems may be required for the syndrome to occur.

Adrenergic alpha-Agonists↗
PubMed1989

Cytotoxic effects of acrylamide and its related compounds assessed by protein content, LDH activity and cumulative glucose consumption of neuron-rich cultures in a chemically defined medium.

Cytotoxicity of acrylamide on neuronal cells cultured in a chemically defined medium was studied with morphological alteration, protein content, LDH activity and cumulative glucose consumption as toxicity indicators. The cumulative glucose consumption was significantly reduced by exposure to acrylamide before the other indicators were affected, suggesting that it would be the most sensitive indicator in the present study and that inhibition of glucose utilization might be one of the mechanisms of acrylamide neurotoxicity. The cumulative glucose consumption was applied for assessing cytotoxicity of acrylamide and its related compounds in neuronal cultures. The ED50 values were 0.8, 5.8, 15.0 mM for acrylamide, N-isopropylacrylamide, and methacrylamide, respectively, which are neurotoxic in in vivo studies. N,N'-methylene-bis-acrylamide, which is not reported to be neurotoxic, however, showed the lowest ED50 value, 0.2 mM, indicating that it was most potently toxic to neuronal cells. The results suggest the necessity of a cautious approach to neurotoxicity assessment from culture studies.

Acrylamides↗
PubMed1989

Allylnitrile: a compound which induces long-term dyskinesia in mice following a single administration.

A single oral dose of allylnitrile (ALN) in mice pretreated with CCl4 induced behavioral abnormalities such as circling, hyperactivity, and head twitching, which lasted for a 4-month observation period. Histopathologically hemorrhage, demyelinated fibers and necrotic neurons were observed in the midbrain and pons 40 to 50 days after the administration of ALN. The head twitching was either reduced by treatment with serotonin and dopamine antagonists or enhanced by a serotonin releaser, suggesting that both serotonin and dopamine systems are involved in the behavioral abnormalities by ALN. These disorders by ALN may be used as an animal model of the dyskinetic syndrome.

Animals↗
PubMed1989

Nitrile-induced behavioral abnormalities in mice.

A single oral dose of crotononitrile or 2-pentenenitrile induced behavioral abnormalities such as circling, hyperactivity and head twitching. Crotononitrile induced the abnormalities in both olive oil- and CCl4 pretreated mice, whereas 2-pentenenitrile induced the abnormalities only in CCl4-pretreated mice. Seven related compounds induced no behavioral abnormality. The head twitching by crotononitrile and 2-pentenenitrile was either reduced by treatment with serotonin and dopamine antagonists, or enhanced by a serotonin releaser, suggesting that both the serotonin and dopamine systems are involved in the behavioral abnormalities induced by these two nitriles.

Animals↗
PubMed1988

The influence of neuronal cells on the development of glutamine synthetase in astrocytes in vitro.

The influence of neurons on the development of astroglial cells was examined in vitro using glutamine synthetase (GS) activity as an index of metabolic maturation. The GS activity in forebrain astrocytes was significantly increased (about 70%) when they were co-cultured with forebrain neuronal cells. A similar effect was also observed when astrocytes from the immature septum, hippocampus or cerebellum were co-cultured with neurons derived from the septal-diagonal band region. The magnitude of the effect was not uniform; the cerebellar astrocytes, with relatively low GS activity, showed a greater (about 290%) quantitative response to the subcortical nerve cells than did the septal (about 115%) or the hippocampal (about 120%) astroglial cells. The addition of conditioned medium derived from neuronal cultures or plating the cells on a substratum of heat-killed nerve cells, elevated the GS activity of astroglial cells by 33% and 39%, respectively. Our results indicate that a trophic factor secreted by neurons and direct contact with the nerve cell matrix, are both involved in the regulation of the differentiation of astrocytes.

Animals↗
PubMed1988

Neurofilament degradation in the nervous system of rats intoxicated with acrylamide, related compounds or 2,5-hexanedione.

Degradation of neurofilament (NF) proteins by Ca2+-activated neutral protease (CANP) was studied in the nervous system of rats treated with neurotoxic or non-neurotoxic compounds. In the tibial nerve, the degradation of NF 68K was depressed by five neurotoxic compounds: acrylamide, N-hydroxymetylacrylamide, N-isopropylacrylamide, methacrylamide and 2,5-hexanedione. A non-neurotoxic compound, diacetone acrylamide, did not show any effect on the degradation. An immunoblot analysis confirmed the reduction in the degradation and revealed a difference in the degradation pattern between the control and acrylamide-treated rats. In the spinal cord, the degradation of the three subunits of NF was depressed in animals treated with acrylamide. Although the exact mechanism of the reduction in the degradation of NF is not yet known, the present results suggest that an inhibitory effect on CANP activity might be relevant to the mechanism of neurotoxic action of acrylamide derivatives.

Acrylamides↗
PubMed1988

Cytotoxicity of acrylamide and related compounds to mouse neuroblastoma and rat schwannoma cells.

Cytotoxicity of acrylamide and related compounds to mouse neuroblastoma N18TG-2 and rat Schwannoma RT4 cells was studied. Of nine test chemicals, acrylamide and N-hydroxymethylacrylamide were most toxic compared with others on the basis of ED50 value. Observation under phase-contrast microscopy revealed that in N18TG-2 acrylamide produced both degeneration of the cells and inhibition of cell growth, and that in RT4 it produced only inhibition of cell growth without causing any marked morphological changes. Dibutyryl cyclic AMP (dBcAMP) reduced the cytotoxicity of acrylamide to both types of cells on the basis of the dose-effect curve. Studies on the subcellular distribution of 14C-acrylamide incorporated showed that more than 90% of the total radioactivity was incorporated in the 15,000 g supernant fraction. Kinetics of acrylamide uptake by N18TG-2 cells showed that in the cells untreated with dBcAMP there were two binding sites with high and low affinity, and that after treatment with dBcAMP the site of high affinity disappeared. The situation was true for RT4 cells, the results indicating that the immature cells are more vulnerable to acrylamide than the mature cells.

Acrylamides↗
PubMed1988

Immunochemical studies of acrylamide-associated neuropathology.

An immunohistochemical study on neurofilaments (NF) in the central and peripheral nervous systems of rats after repeated treatment with acrylamide was done by the avidin-biotin complex method using monoclonal anti-neurofilaments antibodies (68, 160 and 200 kD). Rats were given acrylamide (50 ml/kg) i.p. every day for 8 days. In the cerebrum, NF in perikarya of large nerve cells were weakly stained with all antibodies in both control and treated rats, with no differences between the 2 groups. In the cerebellum, NF of the Purkinje cells were slightly stained with all 3 antibodies. In the treated rats, a marked accumulation of NF in the distal part of the basket cell fibers was detected by 68 kD. In the molecular layer, some parallel fibers were also stained by 68 kD in the treated animals. In the spinal cord, all NF were stained, the staining being clearer in the lower part of the cord in the treated rats. In the peripheral nerve of the treated rats, many axons were segmentally swollen along the entire length of the nerve, especially, in the distal region. In muscle preparations of the treated rats, some neuro-muscular junctions stained with 68 kD were also visible.

Acrylamide↗
PubMed1986

Influence of ethanol on the in vivo and in vitro metabolism of nitriles in mice.

The effect of ethanol on metabolism of 20 nitriles was studied in vivo and in vitro in mice. The hepatic microsomal metabolizing activity for nitriles was at a maximum 13 h after ethanol dosing (4.0 g/kg). Using microsomes from mice pretreated with ethanol under the above conditions, enhancement of the in vitro metabolism of nitriles was 1.00-1.83 compared with the glucose-treated control. When mice were orally given nitriles 13 h after dosing with either ethanol (4.0 g/kg) or glucose (7.0 g/kg), the hepatic metabolizing activity of nitriles for the ethanol-treated group was always higher than that for the glucose group, although no change in the content of hepatic microsomal P-450 was observed between the two groups. However, ethanol added to the incubation mixture inhibited the in vitro metabolism of most nitriles. The results in the present study suggest that ethanol can enhance the acute toxicity of nitriles.

Acrylonitrile↗
PubMed1986

Structure-toxicity relationship of monoketones.

The structure-toxicity relationship of monoketones was examined in mice. In all test compounds, the acute oral toxicity (LD50) was determined under two conditions; control LD50 (LD50-cont.) and carbon tetrachloride (CCl4)-pretreated LD50 (LD50CCl4). LD50-cont. was larger than LD50-CCl4 in all test compounds, the difference being greater in compounds with longer carbon chains than in those with shorter chains. Both LD50-cont. and LD50-CCl4 were parabolic functions of the partition coefficient, log P, i.e., log (1/LD50-cont.) = -0.120(log P)2 + 0.417log P - 1.734 and log(1/LD50-CCl4) = -0.103(log P)2 + 0.462log P - 1.660, and both equations were statistically significant (P less than 0.01). The log Po values were 1.74 for the former and 2.24 for the latter.

Administration, Oral↗
PubMed1985

Structure-acute toxicity relationship of dinitriles in mice.

Acute toxicity and metabolism of seven dinitriles in mice was studied in relation to the chemical structures. The oral LD50 for each nitrile was determined under different conditions for mice pretreated with either carbon tetrachloride (CCl4) or olive oil. All test nitriles were metabolized into cyanide in vivo and in vitro. The cyanide level was variable among the compounds (0.35-0.74 micrograms CN/g brain) at death in the brains of mice, the level for malono- and adiponitrile being comparable to that found in mice killed by dosing with potassium cyanide. After receiving each nitrile, the mean survival time of mice pretreated with CCl4 was prolonged and their brain cyanide level decreased when compared with the corresponding control. With malononitrile, the former did not significantly change and the latter decreased slightly. Brain cyanide levels of control mice at death showed a peak at the lower log P region, while those of CCl4-pretreated animals remained lower independently of log P, with the exception of malononitrile. Microsomal metabolism of nitriles to cyanide was greatly inhibited when microsomes were prepared from livers of mice pretreated with CCl4. The relationship between log (1/LD50-CCl4), LD50 in mice pretreated with CCl4, and log P fits a parabolic plot.

Animals↗
PubMed1985

Percutaneous absorption of [14C]methacrylamide in animals.

Percutaneous absorption of [14C]methacrylamide was determined in rabbits, rats and mice. Radioactivity in blood of rabbits increased rapidly after IV injection, after topical application with a cloth and after direct topical application of a 15 or 5% test solution, suggesting high permeability of the skin for methacrylamide. Radioactivity then began to decrease exponentially within 1 h. Tissue radioactivity 24 h after IV dosing was high in blood, liver and serum, and low in brain, nerve and muscle. The radioactivity was more uniformly distributed with the exception of liver, after application with a cloth and after direct contact than after IV dosing. When the application site was washed with water after direct application, decline of radioactivity in blood was accelerated slightly and a decrease in radioactivity in some tissues was found, although the difference between non-wash and wash groups was not significant in either the declining curve or the tissue radioactivity, with the exception of serum for the latter. Between 25 and 60% of the radioactivity found in tissues was protein-bound after 24 h. Recovery of radioactivity in urine was highest after IV administration, intermediate after direct contact, and lowest after cloth application. Radioactivity in expired air and bile was small. Both radioactivity in tissues and its recovery in urine in rats, and tissue radioactivity in mice, were lower than in rabbits, when adjusted for dose per unit body weight, suggesting lower skin permeability for methacrylamide in the former species.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylamides↗
PubMed1985

Mutagenicity of acrylamide and its analogues in Salmonella typhimurium.

Acrylamide and its 15 analogues have been tested for mutagenicity in 5 TA strains of Salmonella typhimurium. Acrylamide, N-tert-butylacrylamide, crotonamide, diacetone acrylamide, N,N-diethylacrylamide, N,N-dimethylacrylamide, N-hydroxymethylacrylamide, N-methylacrylamide, N-isobutoxymethylacrylamide, N-isopropylacrylamide, methacrylamide, N,N'-methylene-bis-acrylamide and N-tert-octylacrylamide appeared not to be mutagenic in the standard Ames assay both with and without Aroclor 1254-induced S9, and in both the plate incubation and liquid preincubation procedures. Three epoxide analogues, i.e., glycidamide, N,N-diglycidyl acrylamide and glycidyl methacrylamide showed mutagenicity in one or two strains both with and without the S9.

Acrylamides↗
PubMed1985

Effect of acrylamide and related compounds on glycolytic enzymes of rat brain.

The in vitro effect of acrylamide and its analogues on rat brain glycolytic enzymes was examined to elucidate the biochemical lesions responsible for the pathogenesis of acrylamide-induced neuropathy. All test compounds inhibited glyceraldehyde-3-phosphate dehydrogenase, irrespective of their neurotoxicity, and their inhibitory potency was a linear function of the rate constant with reduced glutathione. Phosphofructokinase was also inhibited by some of the test compounds, independently of their neurotoxicity. The rate-limiting enzymes in glycolysis, hexokinase and pyruvate kinase, were not inhibited by acrylamide.

Acrylamides↗
PubMed1984

Studies on the mechanism of acute toxicity of nitriles in mice.

Acute toxicity and metabolism of 21 nitriles in mice were studied in relation to their chemical structures. All the test nitriles liberated cyanide ions both in vivo and in vitro, with the exception of benzonitrile , although the extent of liberation and the effect of carbon tetrachloride (CCl4) pretreatment on the mortality of animals differed among nitriles. From these results, test compounds were tentatively divided into three groups. In group 1 (13 compounds), acute toxicity was greatly reduced by CCl4 pretreatment, in group 2 (seven compounds), toxicity was not significantly changed or was somewhat enhanced, and in group 3, benzonitrile only, toxicity was clearly enhanced. The amount of cyanide was higher (0.68-0.80 microgram CN/g brain) at death in the brains of mice given group-1 compounds, the level being comparable to that found in mice killed by dosing with potassium cyanide. After oral doses of each nitrile, the time course for cyanide levels in the liver varied among the compounds. The difference between group-1 and -2 compounds lay in the dose-cyanide liberation relationship in liver, and in the kinetics for cyanide liberation in the hepatic microsomal enzyme system. Double-reciprocal plots of enzyme activity showed a linear relationship for nitriles of group 1 and a non-linear one for group 2. The relationship between log (1/LD50) and log P for the compounds in group 1 fitted a parabolic plot, while that for compounds in group 2 was linear.

Animals↗
PubMed1984

Structure-toxicity relationship of aliphatic nitriles.

Acute toxicity, in vitro metabolism and structure-toxicity relationship of aliphatic mononitriles were examined in mice pretreated with carbon tetrachloride (CCl4). The LD50 in mice pretreated with CCl4 (LD50-CCl4) was increased in most nitriles compared to that in untreated animals (LD50-cont.) with different degrees among compounds. Microsomal metabolism of nitriles to CN- was completely inhibited when microsomes were prepared from livers of mice pretreated with CCl4. Log (1/LD50-CCl4) was a linear function of partition coefficient, log P, i.e., log (1/LD50-CCl4) = -0.371 log P-0.152, and the equation was statistically significant (P less than 0.01), provided aceto- and 3-hydroxypropionitrile were omitted from the analysis. These two compounds seem to be different from the others in exerting the biological effect.

Animals↗
PubMed1983

Neurotoxicity of acrylamide and related compounds in rats. Effects on rotarod performance, morphology of nerves and neurotubulin.

Neurotoxic properties of acrylamide and seven related compounds in rats were studied with regard to the effects on rotarod performance, morphology of nerves and neurotubulin. Compounds used in the present study were acrylamide, N-hydroxymethylacrylamide, N-isopropylacrylamide, methacrylamide, N-methylacrylamide, crotonamide, diacetone acrylamide, and N-tert-butylacrylamide. Animals were given chemicals in their drinking water for 90 days. Deficit of rotarod performance was produced by five compounds; acrylamide, N-hydroxymethylacrylamide, N-isopropylacrylamide, methacrylamide, and N-methylacrylamide. Morphological changes in tibial and sural nerves, such as shrinkage and loss of myelinated fibres, myelin retraction, and corrugated myelin sheaths, were observed after treatment with these five compounds. Depression of the [3H]colchicine-binding to neurotubulin (the soluble protein) of sciatic nerves was detected after giving these five compounds. After acrylamide dosing, the depression progressed with time. A significant reduction of the colchicine-binding to neurotubulin was also detected in the spinal cord of both the cervical and the lumbar regions, but neither in the brain nor the cerebellum.

Acrylamides↗