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Title: Efeito do uso prolongado de tibolona no endométrio de ratas castradas: análise morfológica e imuno-histoquímica
Keywords: Terapia de Reposição hormonal;  Endométrio;  Ratos;  MEDICINA;  PATOLOGIA INVESTIGATIVA;  Ratos Wistar
Issue Date: 17-Dec-2008
Abstract: Tibolone is a synthetic steroid with selective actions, as estrogen, progestagen, and androgen. It is the first representative of the so-called regulatory activity of selective estrogen in tissues. Some studies suggest that the effect of tibolone is in the same way in both animal models and in humans. The current research is a study of long duration to evaluate the effect of high dose of tibolone in the endometrium of castrated rats. The project aims to demonstrate the effect of tibolone on the endometrium of castrated rats and detect the expression of the Ki-67 protein (cell proliferation). Fifteen castrated albino Wistar rats were used. Tibolone was administered to a group of 9 rats at a dose of 1mg/day per animal which is about 4mg per kg/bw. The drug was administered by esophagic intubation during an uninterrupted period of 20 weeks. The control group was composed of 6 rats, receiving only the vehicle carboxymethylcellulose during the same period. After the 20 weeks, the animals were euthanized and the uterus was removed and examined by histopathology (morphometry and morphology) and immunohistochemistry. The histopathological evaluation was made by the usual technique with the hematoxylin and eosin staining, and expression of Ki-67, by immunohistochemistry. Student's t test and non-parametric Mann-Whitney were used to analyze the results. It was set at 5% (P<0.05) the level of significance to reject the null hypothesis. In the tibolone group, the uterus was well developed and there was significant increase (P&#8804;0.001) of all histomorphometric parameters (thickness of the endometrial epithelium, thickness of endometrial stroma, endometrial area, number of endometrial glands, and thickness of the myometrium). The extent of the area of endometrial tibolone group being 10 times higher than in the control and the absolute number of glands only 11 about 5 times, characterized a higher density of endometrial glands than in the control group. In 8 of 9 cases, the cylindrical epithelium in the endometrial cavity was locally stratified and flattened; this squamous metaplasia covered portions of the internal glands in all cases. The rats in the control group had atrophied uterus. There were little glands of tubular pattern and little intercellular substance. These glands were coated with cubic epithelium which extended to the endometrial surface. The distribution of cells marked by anti-Ki-67 was more frequent in the glandular epithelium, followed by the superficial epithelium. In the group treated with tibolone, the increase in Ki-67 marking was significant (P<0.01). Tibolone administered to castrated rats at high dose (1mg) and by prolonged period (20 weeks) induces proliferative action on the endometrium and change of cell differentiation (squamous metaplasia), however, without showing cellular atypia, or endometrial pre-malignant or malignant lesions, in the studied animals
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