Avaliação toxicológica de compostos orgânicos de telúrio sobre o desenvolvimento pré-natal em camundongos
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/4425 |
Resumo: | It is known that most chemical agents readily cross the placenta and thus may be considered that maternal exposure to external agents can result in toxic effects on embryo-fetal organism. Considering the chemical characteristics of organotellurium compounds, such as lipid solubility and molecular weight that facilitate the cross placental barrier, toxicological studies should be conducted to verify the effects of these compounds on intrauterine development in experimental models. Furthermore, organotellurium compounds have been reported as a promising alternative in health by showing pharmacological properties in different models in which oxidative stress plays a role. Based on these considerations, this thesis investigated the toxic effects of organotellurium compounds, with emphasis on embryonic and fetal development in mice. Article 1, the maternal exposure to diphenyl ditelluride (PhTe)2 at single dose of 60 mg/kg, s.c on GD 4 or GD 14 was embryotoxic in the absence of maternal toxicity but different from the results in rats, which was toxic to the dams and teratogenic to fetus at dose extremely lower than that of mice. These findings showed that pharmacokinetic factors may be involved in susceptibility to teratogenesis differences between rats and mice as well as the period of gestation. In the first manuscript, mice orally exposed to a single dose of 32.8 mg/kg of 1-butyltellurenyl-2-methyl thioheptene (BTMT) at GD 8, one day of the organogenesis period, did not altered the parameters of maternal and fetal oxidative stress, but was embryolethal in the absence of maternal toxicity. These results indicate embryolethality caused by BTMT in mice. In the second manuscript, the exposure to 2-phenylethynyl-butyl tellurium (PEB) in mice at single dose of 10 mg/kg did not induce maternal toxicity, but affect the reproductive sucess at GD 14. In mice, the acute exposure to different organotellurium compounds at doses considerably high showed adverse effects on intrauterine development ranging from discrete embryotoxic insult to embryolethality. We assume that the main reason for the different effects found for PEB and BTMT when compared to (PhTe)2 is that the molecular structures of these organotellurium are very different. Ditellurides are more reactive than tellurides because of the weak Te-Te bond when compared to the Te-carbon bond, since biotransformation process has been seem to be important for the actions of these compounds in vivo. Together, these data suggest that acute exposure to different organic compounds of tellurium induced adverse effects on intrauterine development dependent on the route of administration, the chemical structure of compounds, dose, animal species and period of gestation, therefore making it difficult to compare effects seen in the article with the results of manuscripts 1 and 2, but that does not impossible or discarded the importance of continuity and further research into the pharmacological and toxicological properties of these compounds. |
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Avaliação toxicológica de compostos orgânicos de telúrio sobre o desenvolvimento pré-natal em camundongosToxicological evaluation of organotellurium compounds on prenatal development in micOrganotelúrioGestaçãoDesenvolvimentoToxicidadeCamundongoOrganotelluriumGestationDevelopmentToxicityMiceCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAIt is known that most chemical agents readily cross the placenta and thus may be considered that maternal exposure to external agents can result in toxic effects on embryo-fetal organism. Considering the chemical characteristics of organotellurium compounds, such as lipid solubility and molecular weight that facilitate the cross placental barrier, toxicological studies should be conducted to verify the effects of these compounds on intrauterine development in experimental models. Furthermore, organotellurium compounds have been reported as a promising alternative in health by showing pharmacological properties in different models in which oxidative stress plays a role. Based on these considerations, this thesis investigated the toxic effects of organotellurium compounds, with emphasis on embryonic and fetal development in mice. Article 1, the maternal exposure to diphenyl ditelluride (PhTe)2 at single dose of 60 mg/kg, s.c on GD 4 or GD 14 was embryotoxic in the absence of maternal toxicity but different from the results in rats, which was toxic to the dams and teratogenic to fetus at dose extremely lower than that of mice. These findings showed that pharmacokinetic factors may be involved in susceptibility to teratogenesis differences between rats and mice as well as the period of gestation. In the first manuscript, mice orally exposed to a single dose of 32.8 mg/kg of 1-butyltellurenyl-2-methyl thioheptene (BTMT) at GD 8, one day of the organogenesis period, did not altered the parameters of maternal and fetal oxidative stress, but was embryolethal in the absence of maternal toxicity. These results indicate embryolethality caused by BTMT in mice. In the second manuscript, the exposure to 2-phenylethynyl-butyl tellurium (PEB) in mice at single dose of 10 mg/kg did not induce maternal toxicity, but affect the reproductive sucess at GD 14. In mice, the acute exposure to different organotellurium compounds at doses considerably high showed adverse effects on intrauterine development ranging from discrete embryotoxic insult to embryolethality. We assume that the main reason for the different effects found for PEB and BTMT when compared to (PhTe)2 is that the molecular structures of these organotellurium are very different. Ditellurides are more reactive than tellurides because of the weak Te-Te bond when compared to the Te-carbon bond, since biotransformation process has been seem to be important for the actions of these compounds in vivo. Together, these data suggest that acute exposure to different organic compounds of tellurium induced adverse effects on intrauterine development dependent on the route of administration, the chemical structure of compounds, dose, animal species and period of gestation, therefore making it difficult to compare effects seen in the article with the results of manuscripts 1 and 2, but that does not impossible or discarded the importance of continuity and further research into the pharmacological and toxicological properties of these compounds.É sabido que a maioria dos agentes químicos atravessam facilmente a placenta e, dessa maneira, pode-se considerar que a exposição materna a agentes externos pode resultar em efeitos tóxicos sobre o organismo embrio-fetal. Considerando as características químicas dos compostos orgânicos de telúrio, tais como a solubilidade lipídica e o peso molecular o que possibilitaria a passagem pela barreira placentária, estudos toxicológicos devem ser conduzidos a fim de verificar os efeitos desses compostos sobre o desenvolvimento intrauterino em modelos experimentais. Além do mais, compostos orgânicos de telúrio têm sido vistos como uma alternativa promissora na área da saúde por apresentarem propriedades farmacológicas em diferentes modelos em que o estresse oxidativo está envolvido. Baseado nisso, esta tese propôs verficar o efeito toxicológico de compostos orgânicos de telúrio com ênfase sobre o desenvolvimento embrionário e fetal em camundongos. No artigo 1, a exposição materna ao ditelureto de difenila (PhTe)2 na dose aguda de 60 mg/kg, via subcutânea, foi embriotóxico no 4º e 14º dia de gestação e na ausência de toxicidade materna, mas diferente dos resultados obtidos em ratos (em nosso laboratório), que foi tóxico para as mães e teratogênico para os fetos, com dose extremamente inferiores a de camundongos. Esses achados mostram que fatores farmacocinéticos podem estar envolvidos na diferença de suscetibilidade a teratogênese entre ratos e camundongos, como também o período da gestação. No manuscrito 1, a administração aguda de 1-butiltelurenil-2-metil tiohepteno (BTMT) na dose de 32,8 mg/kg, via oral, no 8º dia de gestação, um dos dias do período da organogênese em camundongos, não alterou os parâmetros de estresse oxidativo materno e fetal, porém foi embrioletal na ausência de toxicidade materna. Esses resultados indicaram a embrioletalidade causada pelo BTMT. No manuscrito 2, a administração de 2-feniletinil-butil telúrio (PEB) na dose aguda por via oral de 10 mg/kg não induz a toxicidade materna, mas afeta o sucesso reprodutivo no 14º dia de gestação. Pode-se supor que a principal razão para os efeitos diferentes encontrados para o PEB e ao BTMT quando comparados com o (PhTe)2, é que a estrutura química dos diteluretos e dos monoteluretos, já estudadas e relatadas na literatura é muito diferente. Isso porque os diteluretos são mais reativos que teluretos por causa da fraca ligação Te-Te quando comparado com a ligação Te-carbono, uma vez que o processo de biotransformação parece ser importante para as ações desses compostos in vivo. Juntos, estes dados sugerem que a exposição aguda aos diferentes compostos orgânicos de telúrio induziu a efeitos adversos sobre o desenvolvimento intrauterino dependentes da via de administração, estrutura química dos compostos, dose, espécie animal e período da gestação, portanto, tornando difícil a comparaçao dos efeitos observados no artigo com os resultados dos manuscritos 1 e 2, mas que não impossibilitam ou descartam a continuidade e a importância de pesquisas adicionais sobre as propriedades farmacológicas e toxicológicas destes compostos.Universidade Federal de Santa MariaBRBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaNogueira, Cristina Waynehttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4728219Y9Puntel, Robson Luizhttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4771515A8Posser, Thaishttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705814H1Mazzanti, Cinthia Melazzo Andradehttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4776635P4Burger, Marilise Escobarhttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4709238P6Roman, Silvane Souza2017-05-022017-05-022011-03-25info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfapplication/pdfROMAN, Silvane Souza. Toxicological evaluation of organotellurium compounds on prenatal development in mic. 2011. 119 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2011.http://repositorio.ufsm.br/handle/1/4425porinfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2017-07-25T14:06:36Zoai:repositorio.ufsm.br:1/4425Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2017-07-25T14:06:36Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Avaliação toxicológica de compostos orgânicos de telúrio sobre o desenvolvimento pré-natal em camundongos Toxicological evaluation of organotellurium compounds on prenatal development in mic |
title |
Avaliação toxicológica de compostos orgânicos de telúrio sobre o desenvolvimento pré-natal em camundongos |
spellingShingle |
Avaliação toxicológica de compostos orgânicos de telúrio sobre o desenvolvimento pré-natal em camundongos Roman, Silvane Souza Organotelúrio Gestação Desenvolvimento Toxicidade Camundongo Organotellurium Gestation Development Toxicity Mice CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Avaliação toxicológica de compostos orgânicos de telúrio sobre o desenvolvimento pré-natal em camundongos |
title_full |
Avaliação toxicológica de compostos orgânicos de telúrio sobre o desenvolvimento pré-natal em camundongos |
title_fullStr |
Avaliação toxicológica de compostos orgânicos de telúrio sobre o desenvolvimento pré-natal em camundongos |
title_full_unstemmed |
Avaliação toxicológica de compostos orgânicos de telúrio sobre o desenvolvimento pré-natal em camundongos |
title_sort |
Avaliação toxicológica de compostos orgânicos de telúrio sobre o desenvolvimento pré-natal em camundongos |
author |
Roman, Silvane Souza |
author_facet |
Roman, Silvane Souza |
author_role |
author |
dc.contributor.none.fl_str_mv |
Nogueira, Cristina Wayne http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4728219Y9 Puntel, Robson Luiz http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4771515A8 Posser, Thais http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705814H1 Mazzanti, Cinthia Melazzo Andrade http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4776635P4 Burger, Marilise Escobar http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4709238P6 |
dc.contributor.author.fl_str_mv |
Roman, Silvane Souza |
dc.subject.por.fl_str_mv |
Organotelúrio Gestação Desenvolvimento Toxicidade Camundongo Organotellurium Gestation Development Toxicity Mice CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
topic |
Organotelúrio Gestação Desenvolvimento Toxicidade Camundongo Organotellurium Gestation Development Toxicity Mice CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
It is known that most chemical agents readily cross the placenta and thus may be considered that maternal exposure to external agents can result in toxic effects on embryo-fetal organism. Considering the chemical characteristics of organotellurium compounds, such as lipid solubility and molecular weight that facilitate the cross placental barrier, toxicological studies should be conducted to verify the effects of these compounds on intrauterine development in experimental models. Furthermore, organotellurium compounds have been reported as a promising alternative in health by showing pharmacological properties in different models in which oxidative stress plays a role. Based on these considerations, this thesis investigated the toxic effects of organotellurium compounds, with emphasis on embryonic and fetal development in mice. Article 1, the maternal exposure to diphenyl ditelluride (PhTe)2 at single dose of 60 mg/kg, s.c on GD 4 or GD 14 was embryotoxic in the absence of maternal toxicity but different from the results in rats, which was toxic to the dams and teratogenic to fetus at dose extremely lower than that of mice. These findings showed that pharmacokinetic factors may be involved in susceptibility to teratogenesis differences between rats and mice as well as the period of gestation. In the first manuscript, mice orally exposed to a single dose of 32.8 mg/kg of 1-butyltellurenyl-2-methyl thioheptene (BTMT) at GD 8, one day of the organogenesis period, did not altered the parameters of maternal and fetal oxidative stress, but was embryolethal in the absence of maternal toxicity. These results indicate embryolethality caused by BTMT in mice. In the second manuscript, the exposure to 2-phenylethynyl-butyl tellurium (PEB) in mice at single dose of 10 mg/kg did not induce maternal toxicity, but affect the reproductive sucess at GD 14. In mice, the acute exposure to different organotellurium compounds at doses considerably high showed adverse effects on intrauterine development ranging from discrete embryotoxic insult to embryolethality. We assume that the main reason for the different effects found for PEB and BTMT when compared to (PhTe)2 is that the molecular structures of these organotellurium are very different. Ditellurides are more reactive than tellurides because of the weak Te-Te bond when compared to the Te-carbon bond, since biotransformation process has been seem to be important for the actions of these compounds in vivo. Together, these data suggest that acute exposure to different organic compounds of tellurium induced adverse effects on intrauterine development dependent on the route of administration, the chemical structure of compounds, dose, animal species and period of gestation, therefore making it difficult to compare effects seen in the article with the results of manuscripts 1 and 2, but that does not impossible or discarded the importance of continuity and further research into the pharmacological and toxicological properties of these compounds. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011-03-25 2017-05-02 2017-05-02 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
ROMAN, Silvane Souza. Toxicological evaluation of organotellurium compounds on prenatal development in mic. 2011. 119 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2011. http://repositorio.ufsm.br/handle/1/4425 |
identifier_str_mv |
ROMAN, Silvane Souza. Toxicological evaluation of organotellurium compounds on prenatal development in mic. 2011. 119 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2011. |
url |
http://repositorio.ufsm.br/handle/1/4425 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria BR Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria BR Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
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UFSM |
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UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
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Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
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1805922144161366016 |