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1. |
In vitroeffects of organophosphorus compounds on calmodulin activity |
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Journal of Applied Toxicology,
Volume 11,
Issue 6,
1991,
Page 391-395
I. Pala,
P. J. S. Vig,
D. Desaiah,
A. Srinivasan,
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摘要:
AbstractIn vitroeffects of organophosphorus compounds (OP), such as malathion (M), methyl parathion (MP) and ethyl parathion (EP), on calmodulin (CaM) activity and its active conformation were studied to understand the mechanism(s) of neurotoxicity, since CaM is known to regulate Ca2+transport and the enzymes involved in signal transduction and nucleotide metabolism. The biological activity of CaM was assessed as a measure of phosphodiesterase (PDE) stimulation. The effect of OP compounds on the active conformation of CaM was determined by studying the binding of fluorescence probes, namelyN‐phenyl‐1‐naphthylamine (NPN), and changes in dansyl‐calmodulin fluorescence. Dansylated calmodulin was also used to study the effect of OP compounds on complex formation between CaM and PDE. All three OP compounds inhibited the CaM activity and its active conformation in a concentration‐dependent manner. Malathion was less effective in comparison to EP and MP, with IC50values of 37 μM, 34.5 μM and 32 μM, respectively, for CaM activity. EP and MP significantly altered NPN and dansyl‐calmodulin fluorescence (50 μM concentrations of OP compounds), whereas M did not show any significant effect on NPN fluorescence. All these compounds significantly affected complex formation between the dansylated CaM and PDE. These results suggest that OP compounds may be interacting with CaM, altering its active conformation, and thus may be inhibiting its biol
ISSN:0260-437X
DOI:10.1002/jat.2550110603
出版商:John Wiley&Sons, Ltd.
年代:1991
数据来源: WILEY
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2. |
Immunotoxicity of tri‐n‐butyltin oxide (TBTO) and tri‐n‐butyltin chloride (TBTC) in the rat |
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Journal of Applied Toxicology,
Volume 11,
Issue 6,
1991,
Page 397-402
G. Bressa,
R. H. Hinton,
S. C. Price,
M. Isbir,
R. S. Ahmed,
P. Grasso,
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摘要:
AbstractIn a 1‐month feeding trial, pure and commercial tri‐n‐butyltin oxide (TBTO) and tri‐n‐butyltin chloride (TBTC) were fed to rats at concentrations of 5 ppm and 25 ppm. At all times, the mean body weight gain and the food consumption was significantly less in rats treated with 25 ppm pure TBTO or pure TBTC as compared to control rats or rats receiving commerical TBTO. Histological examination of the thymus of rats treated for 7 days with TBTO showed atrophy with severe lymphocytic depletion in the cortex. After 28 days of exposure, most of the lesions reversed and the thymus became markedly smaller than in control rats, both in absolute terms and in relation to body weight. Seven days of exposure to TBTO increased liver weight but this change was reversed during a further 3‐week exposure. Tin concentrations were the highest in livers and kidneys. Concentrations in the thymus were less than one‐fifth of hepatic values. Changes in the rats treated with the commercial TBTO were very similar. Rats treated with TBTC showed lower tin levels and less immunotoxicity as compared to those trea
ISSN:0260-437X
DOI:10.1002/jat.2550110604
出版商:John Wiley&Sons, Ltd.
年代:1991
数据来源: WILEY
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3. |
Triorganotin inhibition of rat cardiac adenosine triphosphatases and catecholamine binding |
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Journal of Applied Toxicology,
Volume 11,
Issue 6,
1991,
Page 403-409
Joseph A. Cameron,
Prasada Rao S. Kodavanti,
Srinivas N. Pentyala,
Durisala Desaiah,
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摘要:
AbstractTriorganotins have been reported to affect heme metabolism as well as the cardiovascular system. Our recent studies indicated that these organotins inhibit cardiac sarcoplasmic reticulum Ca2+‐transport and cAMP‐stimulated phosphorylation of specific proteins involved in Ca2+transport, suggesting their interference with cardiac adrenergic function. The present study determines the effect of three organotins–tributyltin bromide (TBT), triethyltin bromide (TET) and trimethyltin chloride (TMT)–on rat cardiac ATPases and catecholamine binding, since these phenomena are involved in cardiac function. Cardiac membrane fraction was prepared from heart ventricles of male Sprague‐Dawley rats. All three organotins inhibited cardiac Na+,K+‐ATPase, [3H]ouabain binding, K+‐activatedp‐nitrophenyl phosphatase (K+‐PNPPase) and oligomycin‐sensitive (OS) and oligomycin‐insensitive (OI) Mg2+‐ATPase in a concentration‐dependent manner. K+‐PNPPase was less sensitive to these triorganotins when compared to Na+K+‐ATPase, suggesting that triorganotins affect the Na+‐pump activity by acting on the Na+‐dependent phosphorylation process. OS Mg2+‐ATPase was more sensitive to these organotins when compared to OI Mg2+‐ATPase, confirming their potent effect on the enzymes of oxidative phosphorylation. The order of potency is TBT>TET>TMT. TET and TMT, but not TBT, inhibited [3H]norepinephrine and [3H]dopamine binding to cardiac membranes in a concentration‐dependent manner, the effect being more with TET. These results suggest that triorganotins inhibit sodium pump activity as well as ATP synthesis. Since Na+,K+‐ATPase is involved in the active transport of catecholamines, triorganotins not only inhibited the catecholamine transport but also to some extent affected catecholamine bindin
ISSN:0260-437X
DOI:10.1002/jat.2550110605
出版商:John Wiley&Sons, Ltd.
年代:1991
数据来源: WILEY
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4. |
Effects of some organophosphorus compounds on the binding of a radioligand (8‐cyclopentyl 1, 3‐[3H]dipropylxanthine) to adenosine receptors in ovine cardiac membranes |
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Journal of Applied Toxicology,
Volume 11,
Issue 6,
1991,
Page 411-414
Wai‐Man Lau,
Maria Szilagyi,
Shirley E. Freeman,
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摘要:
Abstract8‐Cyclopentyl‐1,3‐[3H] dipropylxanthine ([3H]CPX) is a potent radioligand that specifically binds to the A1adenosine receptors. Its high specificity makes it a suitable ligand for the characterization of A1adenosine receptors in tissues with low receptor densities. We have demonstrated that the organophosphorus compounds soman, tabun and sarin, at relatively high concentrations, all bind to the A1adenosine receptors in ovine cardiac membranes withKivalues of 36.7, 328 and 175 μM, respectively. The binding of soman to the receptor site was found to be totally reversible. We suggested that these organophosphorus compounds affect the mechanical responses of the heart through interaction with a potassium channel that does not seem to be closely linked to the A1adenosine rec
ISSN:0260-437X
DOI:10.1002/jat.2550110606
出版商:John Wiley&Sons, Ltd.
年代:1991
数据来源: WILEY
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5. |
Joint toxic action of binary mixtures of osteolathyrogens at malformation‐inducing concentrations forXenopusEmbryos |
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Journal of Applied Toxicology,
Volume 11,
Issue 6,
1991,
Page 415-421
Douglas A. Dawson,
Teresa S. Wilke,
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摘要:
AbstractThe joint action of binary mixtures of the osteolathyrogens semicarbazide (SC), β‐aminopropionitrile (βAPN) and penicillamine (PNC) were determined at malformation‐inducing concentrations forXenopusembryos. Tests were static with renewal every 24 h for the 96‐h test period. Simultaneous tests on each individual component of the binary mixtures alone gave baseline malformation data (EC50) for joint action analyses. Toxic unit analysis and isobole diagrams were used to determine the type of joint action for 3:1, 1:1 and 1:3 mixtures of each combination. The joint action was concentration additive (strictly additive) for SC with βAPN and response additive (less‐than‐additive) for SC with PNC and βAPN with PNC. The joint actions were not changed when only osteolathyrogenic lesions, rather than all types of malformations, were considered. The different specific location and character of PNC lesions, as opposed to those for SC and βAPN, may signify a different type of osteolathyrogenic effect for PNC. The mixture testing approach has potential value in determining compounds that
ISSN:0260-437X
DOI:10.1002/jat.2550110607
出版商:John Wiley&Sons, Ltd.
年代:1991
数据来源: WILEY
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6. |
Validation of a non‐invasive technique to assess immediate or delayed onset of airway hypersensitivity in guinea‐pigs |
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Journal of Applied Toxicology,
Volume 11,
Issue 6,
1991,
Page 423-431
J. Pauluhn,
A. Eben,
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摘要:
AbstractConscious Hartley guinea‐pigs were sensitized with trimellitic anhydride (TMA) or trimeric hexamethylene diisocyanate biuret (Des‐N) by repeated intradermal injections or by inhalation exposure. Immediate‐ and delayed‐onset pulmonary reactions were recorded during/after challenges with the hapten or protein conjugate of the hapten, respectively. The positive control was sensitized and challenged with ovalbumin (OA) by inhalation. Homocytotropic antibodies of the IgGI type were determined to correlate antibody titres and pulmonary responses. Immediate‐onset pulmonary reactions were apparent in guinea‐pigs sensitized by inhalation of TMA and OA. Animals sensitized intradermally with TMA demonstrated more vigorous immediate‐onset reactions than animals sensitized by inhalation. The measurement of breathing parameters demonstrated that the ability to detect immediate‐onset airway hyperreactivity was best when the breathing rate and tidal and minute volumes were measured. None of the measurements for delayed‐onset reactions presented conclusive results, since sensitized as well as naive guinea‐pigs demonstrated a delayed increase of breathing frequency. Antigen‐specific IgG1 antibodies were several orders of magnitude higher in intradermally sensitized animals compared with animals sensitized by inhalation. Although Des‐N‐sensitized guinea‐pigs experienced high IgG1‐antibody titres, no response of pulmonary hypersensitivity could be elicited after hapten or conjugate challenge. In summary, it would appear that pulmonary hypersensitivity depends on factors other than IgGl antibody titres. For the screening of chemicals, the dermal induction and inhalation challenge protocol was revealed to be more sensitive than the inhalation induction and
ISSN:0260-437X
DOI:10.1002/jat.2550110608
出版商:John Wiley&Sons, Ltd.
年代:1991
数据来源: WILEY
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7. |
Difference in liver and serum malathion carboxylesterase and glucose‐6‐phosphatase in detecting carbon tetrachloride‐induced liver damage in rats |
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Journal of Applied Toxicology,
Volume 11,
Issue 6,
1991,
Page 433-435
M. T. Brondeau,
C. Coulais,
J. de Ceaurriz,
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摘要:
AbstractMicrosome, cytosol and serum malathion carboxylesterase (MaCEst) activity was assessed in rats after single i.p. administration of carbon tetrachloride (CCl4) in doses ranging from 0.05 to 1 ml kg−1. MaCEst activities were compared with those of glucose‐6‐phosphatase (G6‐Pase) as an indicator of endoplasmic reticulum damage and serum glutamate dehydrogenase (GLDH) and sorbitol dehydrogenase (SHD) as indicators of liver cytolysis. The data showed a dose‐dependent increase in GLDH and SDH serum activities (175% and 68%) from 0.05 ml kg−1; an increase in serum G6‐Pase (31%) and a decrease in microsomal G6‐Pase (38%) was apparent only after 0.5 or 1.0 ml kg−1doses. MaCEst activity was unaffected. The results demonstrate that, under these experimental conditions, serum and subcellular measurements of MaCEst activity failed to reveal the liver
ISSN:0260-437X
DOI:10.1002/jat.2550110609
出版商:John Wiley&Sons, Ltd.
年代:1991
数据来源: WILEY
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8. |
Biliary excretion of hexachloro‐1,3‐butadiene and its relevance to tissue uptake and renal excretion in male rats |
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Journal of Applied Toxicology,
Volume 11,
Issue 6,
1991,
Page 437-442
J. P. Payan,
J. P. Fabry,
D. Beydon,
J. de Ceaurriz,
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摘要:
AbstractRenal, biliary, pulmonary and faecal excretion experiments were carried out with labelled hexachloro‐1,3‐butadiene ([14C]HCBD) in male Sprague‐Dawley rats, given orally (p.o.) and intravenously (i.v.) in doses of 1 and 100 mg kg−1as a solution in polyethylene glycol. The radioactivity excreted over 72 h was determined in rats fitted with exteriorized biliary cannulae and in rats whose bile ducts remained fully functional, respectively. In addition, bile duct–duodenum cannula‐linked rats, of which the donor was given 100 mg kg−1[14C]HCBD orally and the recipient had also a bile fistula, were examined within 30 h for radioactivity in the excreta, the kidney, the liver and the plasma. In non‐cannulated rats, fractional urinary excretion decreased when the dosage increased and amounted to 23% and 8.6% after i.v. injection or 18.5% and 8.9% after p.o. administration of 1 and 100 mg kg−1, respectively. Pulmonary excretion of radioactivity was<9% and was not affected by the increase in dosage. In bile duct‐cannulated rats, fractional urinary excretions were similar irrespective of the dose and the route of administration and amounted to ca. 7.5% of the dose. Decrease in fractional biliary excretion occurred with increase in dosage (88.7% vs 72%) after i.v. injection and (66.8% vs 58%) after gavage. In cannulated rats, faecal excretion was<0.5% after i.v. injection and accounted for 3% and 16% of the dose after p.o. administration of 1 and 100 mg kg−1, respectively. In rats linked in a cascade fashion, the donors excreted 3%, 45% and 19.5% of the dose in the urine, the bile and the faeces versus 2%, 16.8% and 8.4% for the recipients, respectively. Renal, hepatic and plasma radioactivity concentrations represented 0.26, 0.11 and 0.013% g−1of the dose in the donors versus 0.15, 0.07 and 0.009% g−1of the dose in the recipients. Biliary decline may result from a saturation of the hepatobiliary mechanism after i.v. injection and/or a saturation of gastrointestinal HCBD absorption after p.o. administration. The results indicate that at least 80% of the biliary metabolites of HCBD undergo biliary recycling and constitutes about 40% of renal excretion and tissue uptake of [14C]HCBD at the high dose level. They also support the assumption that decline in fractional urinary excretion with increase in HCBD dosage was unlikely to be due to renal saturation but was probably the result of hepatobiliary saturation and/or defective enterohepatic circul
ISSN:0260-437X
DOI:10.1002/jat.2550110610
出版商:John Wiley&Sons, Ltd.
年代:1991
数据来源: WILEY
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9. |
Depression of iron uptake into erythrocytes in mice by treatment with the combined benzene metabolitesp‐benzoquinone, muconaldehyde and hydroquinone |
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Journal of Applied Toxicology,
Volume 11,
Issue 6,
1991,
Page 443-446
Robert L. Guy,
Peidi Hu,
Gisela Witz,
Bernard D. Goldstein,
Robert Snydert,
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摘要:
AbstractUsing radio‐iron uptake into erythrocytes as a measure of hematopoiesis, it was demonstrated thatp‐benzoquinone (BQ) and muconaldehyde (MUC) are potent inhibitors of bone marrow function in female mice. These two benzene metabolites reduced iron uptake at dosages of<5–6 mg kg−1. The combination of MUC and hydroquinone (HQ) (100 mg kg−1) was additive, reducing iron incorporation to an extent that was the sum of the effect of each chemical given alone. The combined effect of MUC and BQ was significantly less than additive, demonstrating antagonism in the response. Multiple regression was used to study the contributions of the components of binary mixtures of the benzene metabolites (METAB). Data obtained from standard curves of METAB and their mixtures are separable in regression analysis. Thus, for zero interaction of METAB, the responses would be simply additive, while positive and negative interaction would indicate synergy and antagonism, respectively. T‐testing of the data resulted in non‐significant values for the mixture MUC+HQ, indicating zero interaction and an additive response. The negativet‐values obtained for the mixture MUC + BQ, however, indicate negative interaction or an antagonistic response. Since mutually exclusive agents share the same binding sites and occupation of a site by one agent excludes its occupation by another, they cannot interact in producing the effect; combinations of these agents show zero interaction and are simply additive. This suggests that HQ and MUC are mutually exclusive and share the same binding site. Conversely, MUC and BQ are mutually non‐exclusive and this requires the presence of at least two binding sites. These results support the hypothesis that the toxic effects of benzene are produced by several metabolites act
ISSN:0260-437X
DOI:10.1002/jat.2550110611
出版商:John Wiley&Sons, Ltd.
年代:1991
数据来源: WILEY
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10. |
Hydrazine |
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Journal of Applied Toxicology,
Volume 11,
Issue 6,
1991,
Page 447-450
R. von Burg,
T. Stout,
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ISSN:0260-437X
DOI:10.1002/jat.2550110612
出版商:John Wiley&Sons, Ltd.
年代:1991
数据来源: WILEY
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