Efeitos do tratamento com tamoxifeno sobre o peso e composição corporal de ratas normotensas de hipertensas
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Data
2009-03-16
Autores
Lopes, Andressa Bolsoni
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Universidade Federal do Espírito Santo
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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Palavras-chave
Tamoxifen , Estrogen , Corporal metabolism , Adipose tissue , Tamoxifeno , Estrogênio , Metabolismo corporal , Tecido adiposo