Efeitos de compostos orgânicos de selênio sobre o desenvolvimento intra-uterino da prole de ratas wistar

Detalhes bibliográficos
Ano de defesa: 2007
Autor(a) principal: Weis, Simone Nardin lattes
Orientador(a): Zeni, Gilson Rogério lattes
Banca de defesa: Barreto, Katia Padilha lattes, Royes, Luiz Fernando Freire lattes
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de Santa Maria
Programa de Pós-Graduação: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
Departamento: Bioquímica
País: BR
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: http://repositorio.ufsm.br/handle/1/11081
Resumo: Selenium (Se) is an essential trace element for man and is known for its role in regulating growth and development of the fetus and newborn. It is well known that Se deficiency is related to miscarriages and pre-term deliveries. However, it is established that Se compounds, depending of dose, can be highly toxic to several species of animals. The organoselenium compounds, diphenyl diselenide [(PhSe)2] and 3 3- ditrifluoromethyldiphenyl diselenide [(F3CPhSe)2] were the target of this study since they present important pharmacological properties. Therefore, it is necessary to dtudy the effects of these compounds on the embryofetal development. The purpose of the present study was to evaluate the effects of (PhSe)2 and (F3CPhSe)2 administration during the organogenesis period of intrauterine development of Wistar rats. Dams were subcutaneously exposed to (PhSe)2 (1.5, 3.0 or 6.0 mg/kg) or only vehicle (canola oil), from days 6 to 15 of gestation (Article). External and internal fetal examination was performed at gestational day 20. No mortality was observed in fetuses or dams at any (PhSe)2 treatment. A decrease in maternal body weight gain (corrected) was found in all (PhSe)2 groups and also an increase in the liver relative weight were observed in these dams, indicating maternal toxicity. Exposure to (PhSe)2 produced significant changes in fetal body weight and biometry. Furthermore, we verify an increase in the incidence of skeletal alterations of fetuses of all (PhSe)2 doses tested, however, these alterations were considered variations that are generally reversible and is unlikely to adversely affect survival or health. (PhSe)2 was capable to cause some morphological modifications on placentas such as vascular congestion, an increase in leucocyte infiltration and phagocytosis. These effects might have contributed with adverse reproductive outcomes observed in the progeny. In the second work presented in this dissertation (Manuscript), pregnant rats were given, via intragastric intubation, 1, 5 or 10 mg/kg of (F3CPhSe)2 or vehicle (canola oil), from days 6 to 15 of gestation. The parameters evaluated were the same of the first study. Administration of 5 and 10 mg/kg of (F3CPhSe)2 decreased maternal weight gain during pregnancy and this was accompanied by a reduced food consumption in the higher dose. Furthermore, there was an increase in liver absolute and relative weight of dams given the higher dose. These data confirm the liver as the primary target organ for Se compounds exposition. Differently from (PhSe)2 exposure, (F3CPhSe)2 administration did not alter fetal body weight and biometry. However, the compound caused embryolethality in the higher dose tested. This effect seems to be all or none since it led to totally resorption of some litters and the others were not affected by the compound. In this dose level, it was also observed a number of skeletal variations that, equally to (PhSe)2 study, seems unlikely represent survival risks. The placentas morphological analysis revealed that exposure to (F3CPhSe)2 was able to alter placental morphology. On the basis of results mentioned above, we conclude that maternal exposure to (PhSe)2 and (F3CPhSe)2 did not cause externally visible malformations but they were able to increase fetuses skeletal alterations incidence, without affecting fetuses survival. Organoselenium compounds also alter placental morphology that could contribute with adverse reproductive outcomes observed on the progeny.
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spelling 2017-05-022017-05-022007-12-03WEIS, Simone Nardin. Effects of organoselenium compounds on the intrauterine development of wistar rats progeny. 2007. 76 f. Dissertação (Mestrado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2007.http://repositorio.ufsm.br/handle/1/11081Selenium (Se) is an essential trace element for man and is known for its role in regulating growth and development of the fetus and newborn. It is well known that Se deficiency is related to miscarriages and pre-term deliveries. However, it is established that Se compounds, depending of dose, can be highly toxic to several species of animals. The organoselenium compounds, diphenyl diselenide [(PhSe)2] and 3 3- ditrifluoromethyldiphenyl diselenide [(F3CPhSe)2] were the target of this study since they present important pharmacological properties. Therefore, it is necessary to dtudy the effects of these compounds on the embryofetal development. The purpose of the present study was to evaluate the effects of (PhSe)2 and (F3CPhSe)2 administration during the organogenesis period of intrauterine development of Wistar rats. Dams were subcutaneously exposed to (PhSe)2 (1.5, 3.0 or 6.0 mg/kg) or only vehicle (canola oil), from days 6 to 15 of gestation (Article). External and internal fetal examination was performed at gestational day 20. No mortality was observed in fetuses or dams at any (PhSe)2 treatment. A decrease in maternal body weight gain (corrected) was found in all (PhSe)2 groups and also an increase in the liver relative weight were observed in these dams, indicating maternal toxicity. Exposure to (PhSe)2 produced significant changes in fetal body weight and biometry. Furthermore, we verify an increase in the incidence of skeletal alterations of fetuses of all (PhSe)2 doses tested, however, these alterations were considered variations that are generally reversible and is unlikely to adversely affect survival or health. (PhSe)2 was capable to cause some morphological modifications on placentas such as vascular congestion, an increase in leucocyte infiltration and phagocytosis. These effects might have contributed with adverse reproductive outcomes observed in the progeny. In the second work presented in this dissertation (Manuscript), pregnant rats were given, via intragastric intubation, 1, 5 or 10 mg/kg of (F3CPhSe)2 or vehicle (canola oil), from days 6 to 15 of gestation. The parameters evaluated were the same of the first study. Administration of 5 and 10 mg/kg of (F3CPhSe)2 decreased maternal weight gain during pregnancy and this was accompanied by a reduced food consumption in the higher dose. Furthermore, there was an increase in liver absolute and relative weight of dams given the higher dose. These data confirm the liver as the primary target organ for Se compounds exposition. Differently from (PhSe)2 exposure, (F3CPhSe)2 administration did not alter fetal body weight and biometry. However, the compound caused embryolethality in the higher dose tested. This effect seems to be all or none since it led to totally resorption of some litters and the others were not affected by the compound. In this dose level, it was also observed a number of skeletal variations that, equally to (PhSe)2 study, seems unlikely represent survival risks. The placentas morphological analysis revealed that exposure to (F3CPhSe)2 was able to alter placental morphology. On the basis of results mentioned above, we conclude that maternal exposure to (PhSe)2 and (F3CPhSe)2 did not cause externally visible malformations but they were able to increase fetuses skeletal alterations incidence, without affecting fetuses survival. Organoselenium compounds also alter placental morphology that could contribute with adverse reproductive outcomes observed on the progeny.O selênio (Se) é um elemento traço essencial para humanos e desempenha importante função no crescimento e desenvolvimento de fetos e recém-nascidos. Sabese que a deficiência desse elemento pode ocasionar abortos e nascimentos prematuros. Entretanto, os compostos de Se, dependendo da dose, podem ser tóxicos para diversas espécies de animais. Os compostos orgânicos de selênio, disseleneto de difenila [(ØSe)2] e disseleneto de 3'3-ditrifluormetildifenila [(F3CØSe)2], foram os alvos deste estudo, visto que possuem importantes propriedades farmacológicas. Com isso, faz-se necessário o estudo dos efeitos destes compostos sobre o desenvolvimento embriofetal. O objetivo deste estudo foi avaliar os efeitos da administração de (ØSe)2 e (F3CØSe)2 durante o período da organogênese do desenvolvimento intra-uterino de ratas Wistar. No primeiro trabalho, as ratas prenhas foram expostas ao (ØSe)2 (1,5; 3,0 ou 6,0 mg/kg) ou ao seu veículo (óleo de canola) via injeção subcutânea, do 6º ao 15º dia de gestação (Artigo). No 20° dia de gestação foi realizada uma laparotomia para a retirada dos fetos e a observação do aparecimento de malformações morfológicas externas e esqueléticas. Não foram observadas mortes maternas e fetais nos grupos expostos ao (ØSe)2. A exposição causou uma diminuição do ganho de peso corporal materno (corrigido) nas duas maiores doses testadas, além de um aumento no peso relativo do fígado destas ratas, indicando que o composto causou toxicidade materna. A exposição ao ( Se)2 alterou significativamente os parâmetros de desenvolvimento avaliados (peso e medidas corporais fetais). Além disso, verificou-se um aumentou de incidência de alterações na ossificação do esqueleto desses fetos, em todas as doses avaliadas, porém, estas alterações são consideradas variações que são geralmente reversíveis e parecem não apresentar riscos à vida. Observou-se também que as placentas das ratas que foram expostas ao (ØSe)2 apresentavam alterações na morfologia, tais como, congestão vascular, aumento da infiltração leucocitária e uma intensa atividade fagocítica. Estes efeitos parecem ter contribuído para os efeitos adversos encontrados nas proles analisadas. No segundo trabalho apresentado nesta dissertação, as ratas prenhas foram expostas ao (F3CØSe)2 (1; 5 ou 10 mg/kg) ou ao seu veículo (óleo de canola) através de entubação gástrica, do 6º ao 15º dia de gestação (Manuscrito). Foram avaliados os mesmos parâmetros do primeiro trabalho. A administração das doses de 5 e 10 mg/kg de (F3CØSe)2 causou uma diminuição de ganho de peso corporal materno, acompanhada de uma diminuição de consumo de alimento na maior dose administrada. Além disso, as ratas que receberam a maior dose do composto tiveram um aumento do peso do fígado (absoluto e relativo). Estes dados confirmam que o fígado é o órgão alvo da exposição a compostos de Se. Diferentemente da exposição ao (ØSe)2, a administração de (F3CØSe)2 não alterou o peso e as medidas corporais fetais. Entretanto, o composto causou embrioletalidade na maior dose testada. Este efeito parece ser do tipo tudo-ounada, uma vez que levou à reabsorção total de metade das ninhadas estudadas, sendo que a outra metade não foi afetada pelo composto. Nesta dose também foram observadas variações esqueléticas, que igualmente ao estudo com (ØSe)2 parecem não apresentar riscos à vida. A análise morfológica das placentas também revelou que a exposição ao (F3CØSe)2 foi capaz de alterar de forma significativa a morfologia da placenta. Portanto, com base nos resultados encontrados, concluímos que a exposição materna ao (ØSe)2 e ao (F3CØSe)2 não provocou o aparecimento de malformações externas visíveis, porém, aumentou a incidência de alterações esqueléticas nos fetos, alterações essas que não afetam a sobrevivência dos mesmos. A exposição aos organocalcogênios também modificou a morfologia das placentas o que pode ter contribuído para o atraso no desenvolvimento intra-uterino observado nas proles.Conselho Nacional de Desenvolvimento Científico e Tecnológicoapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBRBioquímicaSelênioToxicidadeExposição intra-uterinaPlacenta e ratosSeleniumToxicityIntrauterine exposurePlacenta and ratsCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAEfeitos de compostos orgânicos de selênio sobre o desenvolvimento intra-uterino da prole de ratas wistarEffects of organoselenium compounds on the intrauterine development of wistar rats progenyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisZeni, Gilson Rogériohttp://lattes.cnpq.br/2355575631197937Nogueira, Cristina Waynehttp://lattes.cnpq.br/2877042401245169Barreto, Katia Padilhahttp://lattes.cnpq.br/9635724660722753Royes, Luiz Fernando Freirehttp://lattes.cnpq.br/0543081555633400http://lattes.cnpq.br/7075027666937795Weis, Simone Nardin200800000002400500300500500500b21a898a-0ab0-4f33-b980-2b55ef590b94c7ff2a80-5f6d-426e-a6a1-47db808a3c6cc2b1a64f-5f22-4779-9732-0c543f42b42d75e93ed0-dd8e-4526-a6ea-9b1154752ca33844a51f-1f7f-46ca-93b7-18d1a9c07d2binfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALSIMONE WEIS.pdfapplication/pdf2542763http://repositorio.ufsm.br/bitstream/1/11081/1/SIMONE%20WEIS.pdf86037152d8135fc0263a2bef894a435aMD51TEXTSIMONE WEIS.pdf.txtSIMONE WEIS.pdf.txtExtracted texttext/plain101016http://repositorio.ufsm.br/bitstream/1/11081/2/SIMONE%20WEIS.pdf.txtb7623101f3ffec4fe803d8f46caac9f4MD52THUMBNAILSIMONE WEIS.pdf.jpgSIMONE WEIS.pdf.jpgIM Thumbnailimage/jpeg5578http://repositorio.ufsm.br/bitstream/1/11081/3/SIMONE%20WEIS.pdf.jpg3c2b1097c3ac7f5839af5ee358a04a36MD531/110812023-03-03 12:20:27.022oai:repositorio.ufsm.br:1/11081Repositório Institucionalhttp://repositorio.ufsm.br/PUBhttp://repositorio.ufsm.br/oai/requestopendoar:39132023-03-03T15:20:27Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false
dc.title.por.fl_str_mv Efeitos de compostos orgânicos de selênio sobre o desenvolvimento intra-uterino da prole de ratas wistar
dc.title.alternative.eng.fl_str_mv Effects of organoselenium compounds on the intrauterine development of wistar rats progeny
title Efeitos de compostos orgânicos de selênio sobre o desenvolvimento intra-uterino da prole de ratas wistar
spellingShingle Efeitos de compostos orgânicos de selênio sobre o desenvolvimento intra-uterino da prole de ratas wistar
Weis, Simone Nardin
Selênio
Toxicidade
Exposição intra-uterina
Placenta e ratos
Selenium
Toxicity
Intrauterine exposure
Placenta and rats
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
title_short Efeitos de compostos orgânicos de selênio sobre o desenvolvimento intra-uterino da prole de ratas wistar
title_full Efeitos de compostos orgânicos de selênio sobre o desenvolvimento intra-uterino da prole de ratas wistar
title_fullStr Efeitos de compostos orgânicos de selênio sobre o desenvolvimento intra-uterino da prole de ratas wistar
title_full_unstemmed Efeitos de compostos orgânicos de selênio sobre o desenvolvimento intra-uterino da prole de ratas wistar
title_sort Efeitos de compostos orgânicos de selênio sobre o desenvolvimento intra-uterino da prole de ratas wistar
author Weis, Simone Nardin
author_facet Weis, Simone Nardin
author_role author
dc.contributor.advisor1.fl_str_mv Zeni, Gilson Rogério
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/2355575631197937
dc.contributor.advisor-co1.fl_str_mv Nogueira, Cristina Wayne
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/2877042401245169
dc.contributor.referee1.fl_str_mv Barreto, Katia Padilha
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/9635724660722753
dc.contributor.referee2.fl_str_mv Royes, Luiz Fernando Freire
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/0543081555633400
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/7075027666937795
dc.contributor.author.fl_str_mv Weis, Simone Nardin
contributor_str_mv Zeni, Gilson Rogério
Nogueira, Cristina Wayne
Barreto, Katia Padilha
Royes, Luiz Fernando Freire
dc.subject.por.fl_str_mv Selênio
Toxicidade
Exposição intra-uterina
Placenta e ratos
topic Selênio
Toxicidade
Exposição intra-uterina
Placenta e ratos
Selenium
Toxicity
Intrauterine exposure
Placenta and rats
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
dc.subject.eng.fl_str_mv Selenium
Toxicity
Intrauterine exposure
Placenta and rats
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
description Selenium (Se) is an essential trace element for man and is known for its role in regulating growth and development of the fetus and newborn. It is well known that Se deficiency is related to miscarriages and pre-term deliveries. However, it is established that Se compounds, depending of dose, can be highly toxic to several species of animals. The organoselenium compounds, diphenyl diselenide [(PhSe)2] and 3 3- ditrifluoromethyldiphenyl diselenide [(F3CPhSe)2] were the target of this study since they present important pharmacological properties. Therefore, it is necessary to dtudy the effects of these compounds on the embryofetal development. The purpose of the present study was to evaluate the effects of (PhSe)2 and (F3CPhSe)2 administration during the organogenesis period of intrauterine development of Wistar rats. Dams were subcutaneously exposed to (PhSe)2 (1.5, 3.0 or 6.0 mg/kg) or only vehicle (canola oil), from days 6 to 15 of gestation (Article). External and internal fetal examination was performed at gestational day 20. No mortality was observed in fetuses or dams at any (PhSe)2 treatment. A decrease in maternal body weight gain (corrected) was found in all (PhSe)2 groups and also an increase in the liver relative weight were observed in these dams, indicating maternal toxicity. Exposure to (PhSe)2 produced significant changes in fetal body weight and biometry. Furthermore, we verify an increase in the incidence of skeletal alterations of fetuses of all (PhSe)2 doses tested, however, these alterations were considered variations that are generally reversible and is unlikely to adversely affect survival or health. (PhSe)2 was capable to cause some morphological modifications on placentas such as vascular congestion, an increase in leucocyte infiltration and phagocytosis. These effects might have contributed with adverse reproductive outcomes observed in the progeny. In the second work presented in this dissertation (Manuscript), pregnant rats were given, via intragastric intubation, 1, 5 or 10 mg/kg of (F3CPhSe)2 or vehicle (canola oil), from days 6 to 15 of gestation. The parameters evaluated were the same of the first study. Administration of 5 and 10 mg/kg of (F3CPhSe)2 decreased maternal weight gain during pregnancy and this was accompanied by a reduced food consumption in the higher dose. Furthermore, there was an increase in liver absolute and relative weight of dams given the higher dose. These data confirm the liver as the primary target organ for Se compounds exposition. Differently from (PhSe)2 exposure, (F3CPhSe)2 administration did not alter fetal body weight and biometry. However, the compound caused embryolethality in the higher dose tested. This effect seems to be all or none since it led to totally resorption of some litters and the others were not affected by the compound. In this dose level, it was also observed a number of skeletal variations that, equally to (PhSe)2 study, seems unlikely represent survival risks. The placentas morphological analysis revealed that exposure to (F3CPhSe)2 was able to alter placental morphology. On the basis of results mentioned above, we conclude that maternal exposure to (PhSe)2 and (F3CPhSe)2 did not cause externally visible malformations but they were able to increase fetuses skeletal alterations incidence, without affecting fetuses survival. Organoselenium compounds also alter placental morphology that could contribute with adverse reproductive outcomes observed on the progeny.
publishDate 2007
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dc.identifier.citation.fl_str_mv WEIS, Simone Nardin. Effects of organoselenium compounds on the intrauterine development of wistar rats progeny. 2007. 76 f. Dissertação (Mestrado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2007.
dc.identifier.uri.fl_str_mv http://repositorio.ufsm.br/handle/1/11081
identifier_str_mv WEIS, Simone Nardin. Effects of organoselenium compounds on the intrauterine development of wistar rats progeny. 2007. 76 f. Dissertação (Mestrado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2007.
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