The Experts below are selected from a list of 216 Experts worldwide ranked by ideXlab platform
Enrico Bollo - One of the best experts on this subject based on the ideXlab platform.
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Triphenyltin Acetate induced cytotoxicity and cd4 and cd8 depletion in mouse thymocyte primary cultures
Toxicology, 2001Co-Authors: Mauro Dacasto, Carlo Nebbia, Enzo Cornaglia, Enrico BolloAbstract:Organotin compounds (OTs) find application worldwide as catalysts, stabilizers and biocides. Triphenyltin derivatives (TPs), including the fungicide Triphenyltin Acetate (TPTA), are OTs mostly used in our country. Some OTs were proved to be immunotoxic and in this paper the cytotoxicity, the possible selective activity upon definite lymphocyte subsets as well as the antiproliferative effect of TPTA was investigated in vitro by using primary cultures of mouse thymocytes. TPTA (5, 10 and 25 μM) was cytotoxic to these cells, as demonstrated by the significant (P<0.05) reduction of the cell viability percentage (trypan blue dye exclusion test), the neutral red uptake and the reduction of tetrazolium salts to formazan products (MTT assay). These overt effects were already noticed after 4 h of exposure to TPTA. The fungicide otherwise significantly reduced, after 24 h of incubation, the percentage of mature single positive thymocytes, particularly the CD4+/CD8− one. Finally, a significative dose-dependent inhibition of the T-cell mitogen-induced cell proliferation was observed in thymocytes exposed to 1 and 8 μM TPTA. These results are indicative of the TPTA immunotoxic properties, according to previous published reports concerning the in vitro and in vivo toxicity of some di- and triorganotin compounds.
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in vitro effects of Triphenyltin Acetate tpta on mouse lymphocyte proliferation
Toxicology in Vitro, 2001Co-Authors: Mauro Dacasto, Carlo Nebbia, Enrico BolloAbstract:Organotin compounds (OTs) are used worldwide in industry and in agricultural practice. In Italy, the OT mostly used is the fungicide Triphenyltin Acetate (TPTA), although in past years it has been submitted to revision for occupational and environmental grounds. In the present study, the possible effect of the fungicide on cell proliferation has been investigated, using [(3)H]thymidine incorporation radiometric assay. Mouse thymocytes in primary culture were stimulated for 24 h with T- and B-cell mitogens (concanavalin A, CON A and phytohemagglutinin, PHA or pokeweed mitogen, PWM, respectively). Cultures were then exposed 24 h to 0, 1 and 8 microM TPTA. At the end of incubation, cells were pulsed with methyl-[(3)H]thymidine and harvested for total radioactivity counts after a further 24 h of incubation. An overall dose-dependent significant (P<0.05) reduction of proliferative response was observed with all mitogens tested. Interestingly, CON A proved to be more sensitive (P<0.05) to the TPTA toxic effect compared with PWM and PHA. TPTA is cytotoxic to mouse thymocytes in primary culture, particularly towards the mature lymphocytes (CD4(+) and CD8(+)). The present results support the hypothesis of a TPTA-induced decrease of lymphoproliferative response to T- and B-cell mitogens, previously observed with other OTs.
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Triphenyltin Acetate-induced cytotoxicity and CD4(+) and CD8(+) depletion in mouse thymocyte primary cultures.
Toxicology, 2001Co-Authors: Mauro Dacasto, Carlo Nebbia, Enzo Cornaglia, Enrico BolloAbstract:Organotin compounds (OTs) find application worldwide as catalysts, stabilizers and biocides. Triphenyltin derivatives (TPs), including the fungicide Triphenyltin Acetate (TPTA), are OTs mostly used in our country. Some OTs were proved to be immunotoxic and in this paper the cytotoxicity, the possible selective activity upon definite lymphocyte subsets as well as the antiproliferative effect of TPTA was investigated in vitro by using primary cultures of mouse thymocytes. TPTA (5, 10 and 25 μM) was cytotoxic to these cells, as demonstrated by the significant (P
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Triphenyltin Acetate toxicity : a biochemical and ultrastructural study on mouse thymocytes:
Human & Experimental Toxicology, 1996Co-Authors: Enrico Bollo, Carlo Nebbia, Enzo Cornaglia, L. Ceppa, Bartolomeo Biolatti, Mauro DacastoAbstract:1 Triphenyltin Acetate (TPTA) has been shown to exert in vivo a selective toxic effect on the immune system. To assess in vitro possible alterations induced by TPTA exposure, primary cultures of mouse thymocytes were incubated up to 24 h with graded amounts (1-12 μM) ofthe organotin.2 The cytotoxic activity has been evaluated with the MTT colorimetric assay, the neutral red (NR) assay and the lactic dehydrogenase (LDH) cellular release. Cell pellets were fixed with 2.5% glutaraldehyde, resin-embedded and ultrathin sections were observed through transmission electron microscopy.3 After 2 h of incubation, dose-dependent increases of cytotoxicity were observed in thymocytes submitted to MTT and NR tests (up to 41.43% and 18.9%, respectively), while 22 h later this overt effect on cell viability was noticed merely in cells exposed to 12 μM TPTA. Dose- dependent increases of LDH leakage in the culture medium were observed all throughout the study.4 Morphological investigations revealed features (chro matin con...
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Triphenyltin Acetate tpta induced cytotoxicity to mouse thymocytes
Pharmacological Research, 1994Co-Authors: Mauro Dacasto, Carlo Nebbia, Enrico BolloAbstract:To perform a better investigation of the toxic activity of Triphenyltin Acetate (TPTA) already described in vivo, primary cultures of murine thymocytes were incubated for 2 to 32 h with graded amounts (0.5–8μm) of the triorganotin compound. The cytotoxic activity has been evaluated with the Trypan blue dye exclusion test, the 3-(4,5-dimethyl-thiazol-2-yl)-2,5 diphenyl-tetrazolium bromide (MTT) assay for cell survival and the cellular release of lactate dehydrogenase. Following 2 h of incubation with TPTA, a dose-dependent reduction (P<0.05) of cellular viability occurred and marked increases (P<0.05) of the MTT cytotoxic index and of lactate dehydrogenase leakage were also observed. These findings indicate that TPTA is as cytotoxic to mice thymocytes, as other Triphenyltin derivatives are to other species.
Mauro Dacasto - One of the best experts on this subject based on the ideXlab platform.
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Triphenyltin Acetate induced cytotoxicity and cd4 and cd8 depletion in mouse thymocyte primary cultures
Toxicology, 2001Co-Authors: Mauro Dacasto, Carlo Nebbia, Enzo Cornaglia, Enrico BolloAbstract:Organotin compounds (OTs) find application worldwide as catalysts, stabilizers and biocides. Triphenyltin derivatives (TPs), including the fungicide Triphenyltin Acetate (TPTA), are OTs mostly used in our country. Some OTs were proved to be immunotoxic and in this paper the cytotoxicity, the possible selective activity upon definite lymphocyte subsets as well as the antiproliferative effect of TPTA was investigated in vitro by using primary cultures of mouse thymocytes. TPTA (5, 10 and 25 μM) was cytotoxic to these cells, as demonstrated by the significant (P<0.05) reduction of the cell viability percentage (trypan blue dye exclusion test), the neutral red uptake and the reduction of tetrazolium salts to formazan products (MTT assay). These overt effects were already noticed after 4 h of exposure to TPTA. The fungicide otherwise significantly reduced, after 24 h of incubation, the percentage of mature single positive thymocytes, particularly the CD4+/CD8− one. Finally, a significative dose-dependent inhibition of the T-cell mitogen-induced cell proliferation was observed in thymocytes exposed to 1 and 8 μM TPTA. These results are indicative of the TPTA immunotoxic properties, according to previous published reports concerning the in vitro and in vivo toxicity of some di- and triorganotin compounds.
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in vitro effects of Triphenyltin Acetate tpta on mouse lymphocyte proliferation
Toxicology in Vitro, 2001Co-Authors: Mauro Dacasto, Carlo Nebbia, Enrico BolloAbstract:Organotin compounds (OTs) are used worldwide in industry and in agricultural practice. In Italy, the OT mostly used is the fungicide Triphenyltin Acetate (TPTA), although in past years it has been submitted to revision for occupational and environmental grounds. In the present study, the possible effect of the fungicide on cell proliferation has been investigated, using [(3)H]thymidine incorporation radiometric assay. Mouse thymocytes in primary culture were stimulated for 24 h with T- and B-cell mitogens (concanavalin A, CON A and phytohemagglutinin, PHA or pokeweed mitogen, PWM, respectively). Cultures were then exposed 24 h to 0, 1 and 8 microM TPTA. At the end of incubation, cells were pulsed with methyl-[(3)H]thymidine and harvested for total radioactivity counts after a further 24 h of incubation. An overall dose-dependent significant (P<0.05) reduction of proliferative response was observed with all mitogens tested. Interestingly, CON A proved to be more sensitive (P<0.05) to the TPTA toxic effect compared with PWM and PHA. TPTA is cytotoxic to mouse thymocytes in primary culture, particularly towards the mature lymphocytes (CD4(+) and CD8(+)). The present results support the hypothesis of a TPTA-induced decrease of lymphoproliferative response to T- and B-cell mitogens, previously observed with other OTs.
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Triphenyltin Acetate-induced cytotoxicity and CD4(+) and CD8(+) depletion in mouse thymocyte primary cultures.
Toxicology, 2001Co-Authors: Mauro Dacasto, Carlo Nebbia, Enzo Cornaglia, Enrico BolloAbstract:Organotin compounds (OTs) find application worldwide as catalysts, stabilizers and biocides. Triphenyltin derivatives (TPs), including the fungicide Triphenyltin Acetate (TPTA), are OTs mostly used in our country. Some OTs were proved to be immunotoxic and in this paper the cytotoxicity, the possible selective activity upon definite lymphocyte subsets as well as the antiproliferative effect of TPTA was investigated in vitro by using primary cultures of mouse thymocytes. TPTA (5, 10 and 25 μM) was cytotoxic to these cells, as demonstrated by the significant (P
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Changes in hepatic and renal glutathione-dependent enzyme activities in rabbits and lambs subchronically treated with Triphenyltin Acetate.
Veterinary and human toxicology, 2000Co-Authors: P. Di Simplicio, Mauro Dacasto, Monica Carletti, F. Giannerini, C. NebbiaAbstract:To gain insight into the biochemical mechanisms of organotin toxicity, the effects of oral subchronic exposure (70 d) to Triphenyltin Acetate (TPTA) on hepatic and renal enzymes involved in glutathione metabolism were investigated in rabbits and lambs. Rabbits were offered a diet fortified with 15, 75 or 150 ppm TPTA, whereas lambs were daily given 1 or 7.5 mg/kg TPTA On the whole, rabbits were more susceptible than lambs and in both species hepatic enzymes were affected to a greater extent than renal enzymes. In rabbit liver, glutathione S-transferase activity toward 1,2-dichloro-4-nitrobenzene (DCNB) was enhanced at 15 ppm and depressed at 150 ppm TPTA, whereas selenium-dependent glutathione peroxidase (Se-GPX) decreased in a dose-related manner; glyoxalase II (GII) activity increased to the same extent at 15 or 75 ppm TPTA but was unaffected at 150 ppm TPTA. For renal enzyme activities in rabbits, only GPX activity was significantly inhibited at 150 ppm TPTA. The only statistically significant changes in lambs were a fall in both hepatic GST accepting DCNB as substrate at 7.5 mg/kg and Se-GPX at 1 or 7.5 mg/kg TPTA, and an increase in renal GII activity at 7.5 mg/kg TPTA. These results suggest that depression of important antioxidant enzymes such as GST and GPX are part of the complex mechanism of organotin toxicity.
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Triphenyltin Acetate-mediated in vitro inactivation of rat liver cytochrome P-450.
Journal of toxicology and environmental health. Part A, 1999Co-Authors: Carlo Nebbia, Mauro Dacasto, L. Ceppa, Monica CarlettiAbstract:The in vitro effects of the organotin (OT) compound Triphenyltin Acetate (TPTA) on cytochrome P-450 content and functions were investigated in liver microsomes from untreated, phenobarbital (PB)- or beta-naphthoflavone- (betaNAF) pretreated rats. At a concentration of 0.5 mM, TPTA caused a marked loss in the spectrally detectable content of cytochrome P-450 up to 27% of its original value, along with an increase in the inactive form cytochrome P-420. Both effects were most pronounced in betaNAF-treated microsomes, which showed a shift in the hemoprotein absorption maximum from 448 nm to 451 nm, but in all cases TPTA failed to affect either cytochrome b5 or total heme content, or to increase the production of malondialdehyde. These results suggest that lipid peroxidation of microsomal membranes or damage to the heme moiety should be excluded as contributing factors in the hemoprotein loss. TPTA also produced a concentration-related functional inactivation of cytochrome P-450 that was most pronounced in betaNAF-exposed microsomal preparations, as denoted by a striking reduction in the ethoxyresorufin O-deethylase (EROD) activity (IC50 = 0.088 mM). In contrast, the activities of cytochrome P-450-independent microsomal enzymes such as NADPH cytochrome c reductase and indophenyl Acetate esterase (IPA-EST) were not markedly affected even by 0.5 mM TPTA (-30%). As assessed by Lineweaver-Burk plots, the mechanism of inhibition appeared to be noncompetitive for IPA-EST and of mixed type (competitive-noncompetitive) for EROD. Among sulfhydryl-containing compounds, dithiothreitol was considerably more effective than albumin and reduced glutathione in preventing cytochrome P-450 inactivation and even was able to partially reverse the hemoprotein damage when added after TPTA; glycerol, which is known to protect the hydrophobic environment of cytochrome P-450, was as effective as albumin. This study indicates that TPTA behaves as an almost specific and powerful in vitro inhibitor of cytochrome P-450-dependent monooxygenases, apparently through the interaction with critical sulfhydryl groups of the hemoprotein.
Carlo Nebbia - One of the best experts on this subject based on the ideXlab platform.
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Triphenyltin Acetate induced cytotoxicity and cd4 and cd8 depletion in mouse thymocyte primary cultures
Toxicology, 2001Co-Authors: Mauro Dacasto, Carlo Nebbia, Enzo Cornaglia, Enrico BolloAbstract:Organotin compounds (OTs) find application worldwide as catalysts, stabilizers and biocides. Triphenyltin derivatives (TPs), including the fungicide Triphenyltin Acetate (TPTA), are OTs mostly used in our country. Some OTs were proved to be immunotoxic and in this paper the cytotoxicity, the possible selective activity upon definite lymphocyte subsets as well as the antiproliferative effect of TPTA was investigated in vitro by using primary cultures of mouse thymocytes. TPTA (5, 10 and 25 μM) was cytotoxic to these cells, as demonstrated by the significant (P<0.05) reduction of the cell viability percentage (trypan blue dye exclusion test), the neutral red uptake and the reduction of tetrazolium salts to formazan products (MTT assay). These overt effects were already noticed after 4 h of exposure to TPTA. The fungicide otherwise significantly reduced, after 24 h of incubation, the percentage of mature single positive thymocytes, particularly the CD4+/CD8− one. Finally, a significative dose-dependent inhibition of the T-cell mitogen-induced cell proliferation was observed in thymocytes exposed to 1 and 8 μM TPTA. These results are indicative of the TPTA immunotoxic properties, according to previous published reports concerning the in vitro and in vivo toxicity of some di- and triorganotin compounds.
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in vitro effects of Triphenyltin Acetate tpta on mouse lymphocyte proliferation
Toxicology in Vitro, 2001Co-Authors: Mauro Dacasto, Carlo Nebbia, Enrico BolloAbstract:Organotin compounds (OTs) are used worldwide in industry and in agricultural practice. In Italy, the OT mostly used is the fungicide Triphenyltin Acetate (TPTA), although in past years it has been submitted to revision for occupational and environmental grounds. In the present study, the possible effect of the fungicide on cell proliferation has been investigated, using [(3)H]thymidine incorporation radiometric assay. Mouse thymocytes in primary culture were stimulated for 24 h with T- and B-cell mitogens (concanavalin A, CON A and phytohemagglutinin, PHA or pokeweed mitogen, PWM, respectively). Cultures were then exposed 24 h to 0, 1 and 8 microM TPTA. At the end of incubation, cells were pulsed with methyl-[(3)H]thymidine and harvested for total radioactivity counts after a further 24 h of incubation. An overall dose-dependent significant (P<0.05) reduction of proliferative response was observed with all mitogens tested. Interestingly, CON A proved to be more sensitive (P<0.05) to the TPTA toxic effect compared with PWM and PHA. TPTA is cytotoxic to mouse thymocytes in primary culture, particularly towards the mature lymphocytes (CD4(+) and CD8(+)). The present results support the hypothesis of a TPTA-induced decrease of lymphoproliferative response to T- and B-cell mitogens, previously observed with other OTs.
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Triphenyltin Acetate-induced cytotoxicity and CD4(+) and CD8(+) depletion in mouse thymocyte primary cultures.
Toxicology, 2001Co-Authors: Mauro Dacasto, Carlo Nebbia, Enzo Cornaglia, Enrico BolloAbstract:Organotin compounds (OTs) find application worldwide as catalysts, stabilizers and biocides. Triphenyltin derivatives (TPs), including the fungicide Triphenyltin Acetate (TPTA), are OTs mostly used in our country. Some OTs were proved to be immunotoxic and in this paper the cytotoxicity, the possible selective activity upon definite lymphocyte subsets as well as the antiproliferative effect of TPTA was investigated in vitro by using primary cultures of mouse thymocytes. TPTA (5, 10 and 25 μM) was cytotoxic to these cells, as demonstrated by the significant (P
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Triphenyltin Acetate-mediated in vitro inactivation of rat liver cytochrome P-450.
Journal of toxicology and environmental health. Part A, 1999Co-Authors: Carlo Nebbia, Mauro Dacasto, L. Ceppa, Monica CarlettiAbstract:The in vitro effects of the organotin (OT) compound Triphenyltin Acetate (TPTA) on cytochrome P-450 content and functions were investigated in liver microsomes from untreated, phenobarbital (PB)- or beta-naphthoflavone- (betaNAF) pretreated rats. At a concentration of 0.5 mM, TPTA caused a marked loss in the spectrally detectable content of cytochrome P-450 up to 27% of its original value, along with an increase in the inactive form cytochrome P-420. Both effects were most pronounced in betaNAF-treated microsomes, which showed a shift in the hemoprotein absorption maximum from 448 nm to 451 nm, but in all cases TPTA failed to affect either cytochrome b5 or total heme content, or to increase the production of malondialdehyde. These results suggest that lipid peroxidation of microsomal membranes or damage to the heme moiety should be excluded as contributing factors in the hemoprotein loss. TPTA also produced a concentration-related functional inactivation of cytochrome P-450 that was most pronounced in betaNAF-exposed microsomal preparations, as denoted by a striking reduction in the ethoxyresorufin O-deethylase (EROD) activity (IC50 = 0.088 mM). In contrast, the activities of cytochrome P-450-independent microsomal enzymes such as NADPH cytochrome c reductase and indophenyl Acetate esterase (IPA-EST) were not markedly affected even by 0.5 mM TPTA (-30%). As assessed by Lineweaver-Burk plots, the mechanism of inhibition appeared to be noncompetitive for IPA-EST and of mixed type (competitive-noncompetitive) for EROD. Among sulfhydryl-containing compounds, dithiothreitol was considerably more effective than albumin and reduced glutathione in preventing cytochrome P-450 inactivation and even was able to partially reverse the hemoprotein damage when added after TPTA; glycerol, which is known to protect the hydrophobic environment of cytochrome P-450, was as effective as albumin. This study indicates that TPTA behaves as an almost specific and powerful in vitro inhibitor of cytochrome P-450-dependent monooxygenases, apparently through the interaction with critical sulfhydryl groups of the hemoprotein.
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Triphenyltin Acetate toxicity : a biochemical and ultrastructural study on mouse thymocytes:
Human & Experimental Toxicology, 1996Co-Authors: Enrico Bollo, Carlo Nebbia, Enzo Cornaglia, L. Ceppa, Bartolomeo Biolatti, Mauro DacastoAbstract:1 Triphenyltin Acetate (TPTA) has been shown to exert in vivo a selective toxic effect on the immune system. To assess in vitro possible alterations induced by TPTA exposure, primary cultures of mouse thymocytes were incubated up to 24 h with graded amounts (1-12 μM) ofthe organotin.2 The cytotoxic activity has been evaluated with the MTT colorimetric assay, the neutral red (NR) assay and the lactic dehydrogenase (LDH) cellular release. Cell pellets were fixed with 2.5% glutaraldehyde, resin-embedded and ultrathin sections were observed through transmission electron microscopy.3 After 2 h of incubation, dose-dependent increases of cytotoxicity were observed in thymocytes submitted to MTT and NR tests (up to 41.43% and 18.9%, respectively), while 22 h later this overt effect on cell viability was noticed merely in cells exposed to 12 μM TPTA. Dose- dependent increases of LDH leakage in the culture medium were observed all throughout the study.4 Morphological investigations revealed features (chro matin con...
M Dacasto - One of the best experts on this subject based on the ideXlab platform.
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Biochemical, ultrastructural and molecular characterization of the Triphenyltin Acetate (TPTA)-induced apoptosis in primary cultures of mouse thymocytes
Cell Biology and Toxicology, 2006Co-Authors: E. Bollo, C. Nebbia, E. Cornaglia, R. Guglielmino, S. Sant, P. Pregel, F. Riondato, B. Miniscalco, M DacastoAbstract:Triphenyltin Acetate (TPTA), a triorganotin compound used in agriculture as a biocide, is immunotoxic in vivo and in vitro . The present study was undertaken to ascertain whether apoptosis might play a role in the TPTA toxicity in vitro . Mouse thymocyte primary cultures were exposed to 0, 4 and 8 μmol/L TPTA; methyl prednisolone (1 μmol/L) was used as a positive control. Cell aliquots were harvested after 0, 1, 2, 4, and 8 h and the presence of early or late apoptotic phenomena was checked by (a) morphological investigations; (b) spectrophotometric quantification of fragmented DNA and agarose gel electrophoresis; (c) cell flow cytofluorometry, using an annexin V-FITC kit; and (d) detection of in situ apoptosis by a colorimetric detection kit (Titer-Tacs). TPTA cytotoxicity was also evaluated using the trypan blue dye exclusion test. Morphological investigation indicated apoptosis and/or necrosis. After 8 h of incubation, cells exposed to 4 μmol/L TPTA showed an increase in DNA fragmentation (on electrophoresis), which was confirmed by spectrophotometry ( p < 0.05). Flow cytofluorometry pointed out an early ( p < 0.05) increase of annexin V-positive (apoptotic) cells in TPTA-exposed flasks, whereas at least partly contradictory, results were obtained with the Titer-Tacs kit. Overall, these results provide evidence that TPTA, at low concentrations (4 μmol/L) induces early and late apoptotic phenomena, whereas cells exposed to the highest concentrations (8 μmol/L) are likely to undergo necrosis rather than apoptosis.
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In vitro effects of Triphenyltin Acetate (TPTA) on mouse lymphocyte proliferation.
Toxicology in Vitro, 2001Co-Authors: M Dacasto, C. Nebbia, E. BolloAbstract:Organotin compounds (OTs) are used worldwide in industry and in agricultural practice. In Italy, the OT mostly used is the fungicide Triphenyltin Acetate (TPTA), although in past years it has been submitted to revision for occupational and environmental grounds. In the present study, the possible effect of the fungicide on cell proliferation has been investigated, using [(3)H]thymidine incorporation radiometric assay. Mouse thymocytes in primary culture were stimulated for 24 h with T- and B-cell mitogens (concanavalin A, CON A and phytohemagglutinin, PHA or pokeweed mitogen, PWM, respectively). Cultures were then exposed 24 h to 0, 1 and 8 microM TPTA. At the end of incubation, cells were pulsed with methyl-[(3)H]thymidine and harvested for total radioactivity counts after a further 24 h of incubation. An overall dose-dependent significant (P
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The Comparative Effects of Subchronic Administration of Triphenyltin Acetate (TPTA) on the Hepatic and Renal Drug-Metabolizing Enzymes in Rabbits and Lambs
Veterinary Research Communications, 1997Co-Authors: C. Nebbia, M Dacasto, L. Ceppa, M. Gennaro Soffietti, P. Spinelli, V. Bergo, P. Di SimplicioAbstract:Nebbia, C., Dacasto, M., Ceppa, L., Gennaro Soffietti, M., Spinelli, P., Bergo, V. and Di Simplicio, P., 1997. The comparative effects of subchronic administration of Triphenyltin Acetate (TPTA) on the hepatic and renal drug-metabolizing enzymes in rabbits and lambs. Veterinary Research Communications, 21 (2), 117-125 The purpose of this study was to determine whether subchronic (70 days) oral exposure to moderate to high levels of Triphenyltin Acetate (TPTA), an organotin derivative used worldwide, would affect the microsomal hepatic and renal drug-metabolizing enzymes in rabbits and lambs. Rabbits were offered a diet containing 0, 15, 75 or 150 ppm TPTA, while lambs were daily given 0, 1.5 or 7.5 mg TPTA per kg bw. The tin content in the liver and kidneys was measured by atomic absorption spectrophotometry. In the rabbits' livers, TPTA failed to affect the cytochrome P450 content, or the oxidative, hydrolytic (carboxylesterase) or conjugative (UDPG-transferase) enzyme activities studied. In contrast, a striking dose-related increase in both P450 content and carboxylesterase activity (up to 280%) was detected in the rabbits' kidneys, but the ECOD and EROD activities were respectively unchanged or moderately depressed. None of the enzymes studied showed statistically significant changes in the ovine hepatic or renal subfractions. The results suggest that repeated exposure to TPTA could lead to the induction of a particular P450-isoenzyme in rabbit kidneys which is concerned with the metabolism of endogenous compounds (e.g. steroids, prostaglandins, thromboxanes). The lack of significant tissue- and species-related differences in the concentration of tin supports the hypothesis that the changes observed in the rabbits' kidneys may not have been caused solely by the accumulation of the metal in the tissues.
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The comparative effects of subchronic administration of triphnyltin Acetate (TPTA) on the hepatic and renal drug-metabolizing enzymes in rabbits and lambs.
'Springer Science and Business Media LLC', 1997Co-Authors: C. Nebbia, M Dacasto, L. Ceppa, P. Spinelli, Gennaro M. Soffietti, Bergo And V. P. Di SimplicioAbstract:The purpose of this study was to determine whether subchronic (70 days) oral exposure to moderate to high levels of Triphenyltin Acetate (TPTA), an organotin derivative used worldwide, would affect the microsomal hepatic and renal drug-metabolizing enzymes in rabbits and lambs. Rabbits were offered a diet containing 0, 15, 75 or 150 ppm TPTA, while lambs were daily given 0, 1.5 or 7.5 mg TPTA per kg bw. The tin content in the liver and kidneys was measured by atomic absorption spectrophotometry. In the rabbits' livers, TPTA failed to affect the cytochrome P450 content, or the oxidative, hydrolytic (carboxylesterase) or conjugative (UDPG-transferase) enzyme activities studied. In contrast, a striking dose-related increase in both P450 content and carboxylesterase activity (up to 280%) was detected in the rabbits' kidneys, but the ECOD and EROD activities were respectively unchanged or moderately depressed. None of the enzymes studied showed statistically significant changes in the ovine hepatic or renal subfractions. The results suggest that repeated exposure to TPTA could lead to the induction of a particular P450-isoenzyme in rabbit kidneys which is concerned with the metabolism of endogenous compounds (e.g. steroids, prostaglandins, thromboxanes). The lack of significant tissue- and species-related differences in the concentration of tin supports the hypothesis that the changes observed in the rabbits' kidneys may not have been caused solely by the accumulation of the metal in the tissues
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Triphenyltin Acetate toxicity: a biochemical and ultrastructural study on mouse thymocytes.
Macmillan Magazines Limited:Porters South Crinian Street London N1 9XW United Kingdom:011 44 207 8334000 011 44 171 8434982 Fax: 011 44 207 812358, 1996Co-Authors: E. Bollo, C. Nebbia, L. Ceppa, Bartolomeo Biolatti, E. Cornaglia, M DacastoAbstract:Triphenyltin Acetate (TPTA) has been shown to exert in vivo a selective toxic effect on the immune system. To assess in vitro possible alterations induced by TPTA exposure, primary cultures of mouse thymocytes were incubated up to 24 h with graded amounts (1-12 microM) of the organotin. 2. The cytotoxic activity has been evaluated with the MTT colorimetric assay, the neutral red (NR) assay and the lactic dehydrogenase (LDH) cellular release. Cell pellets were fixed with 2.5% glutaraldehyde, resin-embedded and ultrathin sections were observed through transmission electron microscopy. 3. After 2 h of incubation, dose-dependent increases of cytotoxicity were observed in thymocytes submitted to MTT and NR tests (up to 41.43% and 18.9%, respectively), while 22 h later this overt effect on cell viability was noticed merely in cells exposed to 12 microM TPTA. Dose-dependent increases of LDH leakage in the culture medium were observed all throughout the study. 4. Morphological investigations revealed features (chromatin condensation, cell membranes fragmentation and formation of membrane bound apoptotic bodies) suggestive of apoptosis. 5. This study indicates that TPTA is cytotoxic to mouse thymocytes: morphologically, the rising of apoptosis is likely to be recognized, as previously reported in different in vitro studies with other immunosuppressive agents as dioxin and corticosteroids
E. Bollo - One of the best experts on this subject based on the ideXlab platform.
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Biochemical, ultrastructural and molecular characterization of the Triphenyltin Acetate (TPTA)-induced apoptosis in primary cultures of mouse thymocytes
Cell Biology and Toxicology, 2006Co-Authors: E. Bollo, C. Nebbia, E. Cornaglia, R. Guglielmino, S. Sant, P. Pregel, F. Riondato, B. Miniscalco, M DacastoAbstract:Triphenyltin Acetate (TPTA), a triorganotin compound used in agriculture as a biocide, is immunotoxic in vivo and in vitro . The present study was undertaken to ascertain whether apoptosis might play a role in the TPTA toxicity in vitro . Mouse thymocyte primary cultures were exposed to 0, 4 and 8 μmol/L TPTA; methyl prednisolone (1 μmol/L) was used as a positive control. Cell aliquots were harvested after 0, 1, 2, 4, and 8 h and the presence of early or late apoptotic phenomena was checked by (a) morphological investigations; (b) spectrophotometric quantification of fragmented DNA and agarose gel electrophoresis; (c) cell flow cytofluorometry, using an annexin V-FITC kit; and (d) detection of in situ apoptosis by a colorimetric detection kit (Titer-Tacs). TPTA cytotoxicity was also evaluated using the trypan blue dye exclusion test. Morphological investigation indicated apoptosis and/or necrosis. After 8 h of incubation, cells exposed to 4 μmol/L TPTA showed an increase in DNA fragmentation (on electrophoresis), which was confirmed by spectrophotometry ( p < 0.05). Flow cytofluorometry pointed out an early ( p < 0.05) increase of annexin V-positive (apoptotic) cells in TPTA-exposed flasks, whereas at least partly contradictory, results were obtained with the Titer-Tacs kit. Overall, these results provide evidence that TPTA, at low concentrations (4 μmol/L) induces early and late apoptotic phenomena, whereas cells exposed to the highest concentrations (8 μmol/L) are likely to undergo necrosis rather than apoptosis.
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Triphenyltin Acetate-induced cytotoxicity and CD4+ and CD8+ depletion in mouse thymocyte primary cultures
'Elsevier BV', 2001Co-Authors: Dacasto M., Enzo Cornaglia, C. Nebbia, E. BolloAbstract:Organotin compounds (OTs) find application worldwide as catalysts, stabilizers and biocides. Triphenyltin derivatives (TPs), including the fungicide Triphenyltin Acetate (TPTA), are OTs mostly used in our country. Some OTs were proved to be immunotoxic and in this paper the cytotoxicity, the possible selective activity upon definite lymphocyte subsets as well as the antiproliferative effect of TPTA was investigated in vitro by using primary cultures of mouse thymocytes. TPTA (5, 10 and 25 microM) was cytotoxic to these cells, as demonstrated by the significant (P
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In vitro effects of Triphenyltin Acetate (TPTA) on mouse lymphocyte proliferation.
Toxicology in Vitro, 2001Co-Authors: M Dacasto, C. Nebbia, E. BolloAbstract:Organotin compounds (OTs) are used worldwide in industry and in agricultural practice. In Italy, the OT mostly used is the fungicide Triphenyltin Acetate (TPTA), although in past years it has been submitted to revision for occupational and environmental grounds. In the present study, the possible effect of the fungicide on cell proliferation has been investigated, using [(3)H]thymidine incorporation radiometric assay. Mouse thymocytes in primary culture were stimulated for 24 h with T- and B-cell mitogens (concanavalin A, CON A and phytohemagglutinin, PHA or pokeweed mitogen, PWM, respectively). Cultures were then exposed 24 h to 0, 1 and 8 microM TPTA. At the end of incubation, cells were pulsed with methyl-[(3)H]thymidine and harvested for total radioactivity counts after a further 24 h of incubation. An overall dose-dependent significant (P
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Triphenyltin Acetate toxicity: a biochemical and ultrastructural study on mouse thymocytes.
Macmillan Magazines Limited:Porters South Crinian Street London N1 9XW United Kingdom:011 44 207 8334000 011 44 171 8434982 Fax: 011 44 207 812358, 1996Co-Authors: E. Bollo, C. Nebbia, L. Ceppa, Bartolomeo Biolatti, E. Cornaglia, M DacastoAbstract:Triphenyltin Acetate (TPTA) has been shown to exert in vivo a selective toxic effect on the immune system. To assess in vitro possible alterations induced by TPTA exposure, primary cultures of mouse thymocytes were incubated up to 24 h with graded amounts (1-12 microM) of the organotin. 2. The cytotoxic activity has been evaluated with the MTT colorimetric assay, the neutral red (NR) assay and the lactic dehydrogenase (LDH) cellular release. Cell pellets were fixed with 2.5% glutaraldehyde, resin-embedded and ultrathin sections were observed through transmission electron microscopy. 3. After 2 h of incubation, dose-dependent increases of cytotoxicity were observed in thymocytes submitted to MTT and NR tests (up to 41.43% and 18.9%, respectively), while 22 h later this overt effect on cell viability was noticed merely in cells exposed to 12 microM TPTA. Dose-dependent increases of LDH leakage in the culture medium were observed all throughout the study. 4. Morphological investigations revealed features (chromatin condensation, cell membranes fragmentation and formation of membrane bound apoptotic bodies) suggestive of apoptosis. 5. This study indicates that TPTA is cytotoxic to mouse thymocytes: morphologically, the rising of apoptosis is likely to be recognized, as previously reported in different in vitro studies with other immunosuppressive agents as dioxin and corticosteroids
