Efeitos do tratamento com tamoxifeno sobre o peso e composição corporal de ratas normotensas de hipertensas

Detalhes bibliográficos
Autor(a) principal: Lopes, Andressa Bolsoni
Data de Publicação: 2009
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
Texto Completo: http://repositorio.ufes.br/handle/10/7917
Resumo: The tamoxifen, a nonsteroidal antiestrogenic agent classified like selective estrogen receptor modulator (SERM), has been widely used since the 1970s in adjuvant hormonal treatment of primary breast cancer. Paradoxically this SERM is known for produce agonistic effects against the estrogen in uterus, bone, liver and fat metabolism. The actions agonist or antagonists of the SERMs depends of its interaction with α and β estrogen receptor. Changes on the body weight and metabolism have been observed in women during the treatment of the cancer of breast. The estrogen, it is able to modulate the adipose tissue in its different stages. Studies in women and in experimental animals show that the replacement with estrogen is responsible for the reduction of the visceral adipose deposition and the stimulation of the subcutaneous adipose tissue. This evidence indicates an important paper of the estrogen in the modulation of the lipolytic and / or lipogenic effects in this adipose tissue. The objective of the present study was to investigate the causes and mechanisms responsible for the loss of body weight promoted by the chronic treatment with tamoxifen in normotensive and hypertensive, ooforectomized and non ooforectomized rats. Female normotensive (Wistar) and spontaneously hypertensive rats (SHR), 4-week-old were used in this study. Both, Wistar and SHR were classified in 8 differents groups: normotensive control (NC), normotensive treated (NT), normotensive ovariectomized control (NOC), normotensive ovarietomized treated (NOT), SHR controls (SC), SHR treated (ST), SHR ovariectomized controls (SOC) and SHR ovariectomized treated (SOT), n=10 in each group. The treatment began in the 47º day of life of the rats, seven days after gonadectomy. The Tamoxifen was administered once a day by gavage (1mg/Kg) during 90 days. In the control groups was done 0,9% of saline, as vehicle. Weekly the body weight was monitored. On the final of the treatment the animals were sacrificed by decapitation. Immediately samples were removed the blood, visceral fat, muscle Soleus and femur. The Tamoxifen promoted a minor gain of body weight specifically due to the reduction on the visceral adipose tissue. Its possible that the modifications of the adipose mass was caused directly by agonist actions on the estrogen receptors, or indirectly for increase of the metabolism because of the thyroid hormones. We did not observe alteration on the dry weight of the proteins concentration in the muscle Soleus. Also did not occurred modification in the serum total proteins or its fractions. The major weight of femur in the animals treated was consequent to estrogenic agonist effect of this drug. We did not observe modify in the serum levels of the LPL, but the levels of TG in the ooforectomized and treated animals were significantly major. It’s possible that the Tamoxifen promoves like-estrogens actions in the hepatic tissue. This explains its alterations on the lipoproteins and serum lipids. The elevated serum levels of T4 in the Tamoxifen groups could be by direct or indirect actions of tamoxifen on thyroid gland. Furthermore news studies probably will clarify the specific action of the Tamoxifen on the adipose visceral tissue demonstrated in this study
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spelling Abreu, Glaucia Rodrigues deLopes, Andressa BolsoniBotion, Leida MariaGouvea, Sonia Alves2018-08-01T22:58:30Z2018-08-012018-08-01T22:58:30Z2009-03-16The tamoxifen, a nonsteroidal antiestrogenic agent classified like selective estrogen receptor modulator (SERM), has been widely used since the 1970s in adjuvant hormonal treatment of primary breast cancer. Paradoxically this SERM is known for produce agonistic effects against the estrogen in uterus, bone, liver and fat metabolism. The actions agonist or antagonists of the SERMs depends of its interaction with α and β estrogen receptor. Changes on the body weight and metabolism have been observed in women during the treatment of the cancer of breast. The estrogen, it is able to modulate the adipose tissue in its different stages. Studies in women and in experimental animals show that the replacement with estrogen is responsible for the reduction of the visceral adipose deposition and the stimulation of the subcutaneous adipose tissue. This evidence indicates an important paper of the estrogen in the modulation of the lipolytic and / or lipogenic effects in this adipose tissue. The objective of the present study was to investigate the causes and mechanisms responsible for the loss of body weight promoted by the chronic treatment with tamoxifen in normotensive and hypertensive, ooforectomized and non ooforectomized rats. Female normotensive (Wistar) and spontaneously hypertensive rats (SHR), 4-week-old were used in this study. Both, Wistar and SHR were classified in 8 differents groups: normotensive control (NC), normotensive treated (NT), normotensive ovariectomized control (NOC), normotensive ovarietomized treated (NOT), SHR controls (SC), SHR treated (ST), SHR ovariectomized controls (SOC) and SHR ovariectomized treated (SOT), n=10 in each group. The treatment began in the 47º day of life of the rats, seven days after gonadectomy. The Tamoxifen was administered once a day by gavage (1mg/Kg) during 90 days. In the control groups was done 0,9% of saline, as vehicle. Weekly the body weight was monitored. On the final of the treatment the animals were sacrificed by decapitation. Immediately samples were removed the blood, visceral fat, muscle Soleus and femur. The Tamoxifen promoted a minor gain of body weight specifically due to the reduction on the visceral adipose tissue. Its possible that the modifications of the adipose mass was caused directly by agonist actions on the estrogen receptors, or indirectly for increase of the metabolism because of the thyroid hormones. We did not observe alteration on the dry weight of the proteins concentration in the muscle Soleus. Also did not occurred modification in the serum total proteins or its fractions. The major weight of femur in the animals treated was consequent to estrogenic agonist effect of this drug. We did not observe modify in the serum levels of the LPL, but the levels of TG in the ooforectomized and treated animals were significantly major. It’s possible that the Tamoxifen promoves like-estrogens actions in the hepatic tissue. This explains its alterations on the lipoproteins and serum lipids. The elevated serum levels of T4 in the Tamoxifen groups could be by direct or indirect actions of tamoxifen on thyroid gland. Furthermore news studies probably will clarify the specific action of the Tamoxifen on the adipose visceral tissue demonstrated in this studyO tamoxifeno, um agente antiestrogênico não esteroidal, classificado como Modulador Seletivo dos Receptores de Estrogênio (SERMs), tem sido utilizado na prática clínica desde 1970 no tratamento adjuvante para o câncer de mama. Controversamente este SERM possui ações estrogênicas agonistas em diferentes tecidos, como útero, ossos e fígado, e ainda sobre o metabolismo lipídico. As ações agonistas ou antagonistas dos SERMs dependem de sua interação com receptor de estrogênio α and β. Mudanças ponderais e metabólicas têm sido observadas em mulheres durante tratamento para o câncer de mama. O estrogênio, por sua vez, é capaz de modular o tecido adiposo em seus diferentes sítios. Estudos em humanos e em animais experimentais mostram que a reposição com estrogênio leva a redução da deposição de tecido adiposo visceral e ganho de tecido adiposo subcutâneo. Tais evidências apontam para um importante papel do estrogênio na modulação do tecido adiposo branco via lipólise e/ou lipogênese. O objetivo deste estudo foi investigar as causas e mecanismos responsáveis pela perda ponderal promovido pelo tratamento crônico com tamoxifeno em ratas normotensas e hipertensas, ooforectomizadas e não ooforectomizadas. Para este estudo utilizamos ratas Wistar e SHR, com 4 semanas de idade, divididas nos seguintes grupos: ratas normotensas controles (NC), tratadas (NT), ooforectomizadas controles (NOC) e ooforectomizadas tratadas (NOT); e ratas SHR controles (SC), tratadas (ST), ooforectomizadas controles (SOC) e ooforectomizadas tratadas (SOT). O tratamento foi iniciado no 47 º dia de vida, sete dias após cirurgia para ooforectomia. O Tamoxifeno foi administrado uma vez por dia, por via oral (gavage) (1mg/Kg), durante 90 dias consecutivos. Nos grupos controle o veículo administrado foi salina a 0,9 %. O peso corporal foi monitorado semanalmente. E ao fim do tratamento com tamoxifeno os animais foram sacrificados por decapitação e imediatamente removidos os seguintes tecidos: sangue, adiposo visceral, músculo soleus e fêmur. Nossos resultados demonstram que o tamoxifeno promoveu menor ganho de peso corporal provavelmente devido à redução tecido adiposo visceral (NC 49,39±0,9 mg/g; NT 41,5±1,77 mg/g; NOC 73,8±2,61 mg/g e NOT 28,2±1,61 mg/g). As modificações da massa adiposa possivelmente ocorrem por ações agonistas diretas nos receptores de estrogênio do tecido adiposo visceral e indiretamente por aumento do metabolismo via hormônios tireoidianos. Não observamos alterações no peso seco e a concentração protéica do músculo sóleo, bem como, nas proteínas séricas totais e frações. O peso do fêmur de animais ooforectomizados tratados foi superior ao peso do grupo ooforectomizados controles por ações agonistas nos receptores de estrogênio dos ossos. Foi observado elevação dos níveis de TG nos animais ooforectomizados e tratados. Níveis séricos elevados de T4 total por ações diretas nos receptores de estrogênio da glândula tireóide foram encontrados. Futuros estudos deverão esclarecer especificamente o sítio de ação do tamoxifeno responsável pela alterações no tecido adiposo visceral apontados nesse estudo.Texthttp://repositorio.ufes.br/handle/10/7917porUniversidade Federal do Espírito SantoMestrado em Ciências FisiológicasPrograma de Pós-Graduação em Ciências FisiológicasUFESBRCentro de Ciências da SaúdeTamoxifenEstrogenCorporal metabolismAdipose tissueTamoxifenoEstrogênioMetabolismo corporalTecido adiposoFisiologia612Efeitos do tratamento com tamoxifeno sobre o peso e composição corporal de ratas normotensas de hipertensasinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)instname:Universidade Federal do Espírito Santo (UFES)instacron:UFESORIGINALtese_3087_Dissertação Andressa Bolsoni Lopes.pdfapplication/pdf575533http://repositorio.ufes.br/bitstreams/ca89dc6b-8789-47c9-96cd-52e0fb00c773/downloadeac49416d3aa3bc9d444649166cde54cMD5110/79172024-07-16 17:09:04.374oai:repositorio.ufes.br:10/7917http://repositorio.ufes.brRepositório InstitucionalPUBhttp://repositorio.ufes.br/oai/requestopendoar:21082024-10-15T18:01:17.213159Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) - Universidade Federal do Espírito Santo (UFES)false
dc.title.none.fl_str_mv Efeitos do tratamento com tamoxifeno sobre o peso e composição corporal de ratas normotensas de hipertensas
title Efeitos do tratamento com tamoxifeno sobre o peso e composição corporal de ratas normotensas de hipertensas
spellingShingle Efeitos do tratamento com tamoxifeno sobre o peso e composição corporal de ratas normotensas de hipertensas
Lopes, Andressa Bolsoni
Tamoxifen
Estrogen
Corporal metabolism
Adipose tissue
Tamoxifeno
Estrogênio
Metabolismo corporal
Tecido adiposo
Fisiologia
612
title_short Efeitos do tratamento com tamoxifeno sobre o peso e composição corporal de ratas normotensas de hipertensas
title_full Efeitos do tratamento com tamoxifeno sobre o peso e composição corporal de ratas normotensas de hipertensas
title_fullStr Efeitos do tratamento com tamoxifeno sobre o peso e composição corporal de ratas normotensas de hipertensas
title_full_unstemmed Efeitos do tratamento com tamoxifeno sobre o peso e composição corporal de ratas normotensas de hipertensas
title_sort Efeitos do tratamento com tamoxifeno sobre o peso e composição corporal de ratas normotensas de hipertensas
author Lopes, Andressa Bolsoni
author_facet Lopes, Andressa Bolsoni
author_role author
dc.contributor.advisor1.fl_str_mv Abreu, Glaucia Rodrigues de
dc.contributor.author.fl_str_mv Lopes, Andressa Bolsoni
dc.contributor.referee1.fl_str_mv Botion, Leida Maria
dc.contributor.referee2.fl_str_mv Gouvea, Sonia Alves
contributor_str_mv Abreu, Glaucia Rodrigues de
Botion, Leida Maria
Gouvea, Sonia Alves
dc.subject.eng.fl_str_mv Tamoxifen
Estrogen
Corporal metabolism
Adipose tissue
topic Tamoxifen
Estrogen
Corporal metabolism
Adipose tissue
Tamoxifeno
Estrogênio
Metabolismo corporal
Tecido adiposo
Fisiologia
612
dc.subject.por.fl_str_mv Tamoxifeno
Estrogênio
Metabolismo corporal
Tecido adiposo
dc.subject.cnpq.fl_str_mv Fisiologia
dc.subject.udc.none.fl_str_mv 612
description The tamoxifen, a nonsteroidal antiestrogenic agent classified like selective estrogen receptor modulator (SERM), has been widely used since the 1970s in adjuvant hormonal treatment of primary breast cancer. Paradoxically this SERM is known for produce agonistic effects against the estrogen in uterus, bone, liver and fat metabolism. The actions agonist or antagonists of the SERMs depends of its interaction with α and β estrogen receptor. Changes on the body weight and metabolism have been observed in women during the treatment of the cancer of breast. The estrogen, it is able to modulate the adipose tissue in its different stages. Studies in women and in experimental animals show that the replacement with estrogen is responsible for the reduction of the visceral adipose deposition and the stimulation of the subcutaneous adipose tissue. This evidence indicates an important paper of the estrogen in the modulation of the lipolytic and / or lipogenic effects in this adipose tissue. The objective of the present study was to investigate the causes and mechanisms responsible for the loss of body weight promoted by the chronic treatment with tamoxifen in normotensive and hypertensive, ooforectomized and non ooforectomized rats. Female normotensive (Wistar) and spontaneously hypertensive rats (SHR), 4-week-old were used in this study. Both, Wistar and SHR were classified in 8 differents groups: normotensive control (NC), normotensive treated (NT), normotensive ovariectomized control (NOC), normotensive ovarietomized treated (NOT), SHR controls (SC), SHR treated (ST), SHR ovariectomized controls (SOC) and SHR ovariectomized treated (SOT), n=10 in each group. The treatment began in the 47º day of life of the rats, seven days after gonadectomy. The Tamoxifen was administered once a day by gavage (1mg/Kg) during 90 days. In the control groups was done 0,9% of saline, as vehicle. Weekly the body weight was monitored. On the final of the treatment the animals were sacrificed by decapitation. Immediately samples were removed the blood, visceral fat, muscle Soleus and femur. The Tamoxifen promoted a minor gain of body weight specifically due to the reduction on the visceral adipose tissue. Its possible that the modifications of the adipose mass was caused directly by agonist actions on the estrogen receptors, or indirectly for increase of the metabolism because of the thyroid hormones. We did not observe alteration on the dry weight of the proteins concentration in the muscle Soleus. Also did not occurred modification in the serum total proteins or its fractions. The major weight of femur in the animals treated was consequent to estrogenic agonist effect of this drug. We did not observe modify in the serum levels of the LPL, but the levels of TG in the ooforectomized and treated animals were significantly major. It’s possible that the Tamoxifen promoves like-estrogens actions in the hepatic tissue. This explains its alterations on the lipoproteins and serum lipids. The elevated serum levels of T4 in the Tamoxifen groups could be by direct or indirect actions of tamoxifen on thyroid gland. Furthermore news studies probably will clarify the specific action of the Tamoxifen on the adipose visceral tissue demonstrated in this study
publishDate 2009
dc.date.issued.fl_str_mv 2009-03-16
dc.date.accessioned.fl_str_mv 2018-08-01T22:58:30Z
dc.date.available.fl_str_mv 2018-08-01
2018-08-01T22:58:30Z
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dc.publisher.none.fl_str_mv Universidade Federal do Espírito Santo
Mestrado em Ciências Fisiológicas
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dc.publisher.department.fl_str_mv Centro de Ciências da Saúde
publisher.none.fl_str_mv Universidade Federal do Espírito Santo
Mestrado em Ciências Fisiológicas
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