Efeitos cardiovasculares e renais promovidos pelo tratamento crônico com tamoxifeno em ratas ooforectomizadas, normotensas e espontanemente hipertensas
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Data
2007-08-22
Autores
Sipolatti, Walckiria Garcia Romero
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Universidade Federal do Espírito Santo
Resumo
Cardiovascular diseases and breast cancer strike a large proportion of Brazilian women, especially at the post-menopause period. As both conditions afflict the same age group with corresponding health risks, there is a need for testing women with breast cancer for potential heart problems. Although estrogen is associated with a decrease in cardiovascular risks, it has also been identified as a contributor to the development of breast cancer in women. Tamoxifen was approved in 1998 for the treatment of breast cancer and is used for women at high risk of contralateral breast cancer. The drug acts as an estrogen receptor agonist in some tissues and as an antagonist in others and is part of a class of medication known as SERMs - selective estrogen receptor modulators. This study aimed at evaluating the effects of tamoxifen on body metabolism, renal function, cardiovascular system and hepatic function. The experiment was done with 36 female rats, surgically castrated, dived into 4 groups (n=9): Wistar control (WC), Wistar treated with tamoxifen (WT); spontaneous hypertensive rats – SHR control (SC), SHR treated with tamoxifen (ST). Rats were kept in metabolic cages for 90 days with free access to water and chow. Tamoxifen was administered at a concentration of 0.1 mg/day/100 g the rats’ body weight. Ingestion of water, dieresis and chow consumption were monitored and recorded on a daily basis, while body weight was weekly checked to adjust the drug regimen. Following treatment, rats were anesthetized with ketamin, (10 mg/kg) and xylozine (50 mg/kg) and catheterization of both the femoral artery and carotid artery (with the cannula until to the left ventricle) was performed an 24 hours later, with rats awake, mean arterial pressure (MAP) and myocardial contractility index were measured in maximum developed pressure during the isovolumetric phase (dP/dtmax). Our findings suggest that the body weight gain in tamoxifen-treated rats was significantly lower than in the control group, despite the fact that there was no difference in chow consumption. There was also no difference in the relation between liquid intake and urinary excretion in the groups. As to renal weight, the ST group showed a marked loss. Serum levels of sodium, potassium and creatinine remained unaltered after treatment. Histopathological analysis of the renal blade revealed no differences between hypertensive and normotensive groups. Heart rate (HR) and MAP decreased significantly in the ST group, followed by a decrease in dP/dtmax. The humid weight of the left ventricle was also significantly lower in the ST group as compared to the control group, but there were no alterations in the Wistar group. Treatment with tamofixen increased HDL cholesterol in the ST group when compared to the SC group, but again there were no alterations in the Wistar group. LDL cholesterol and total cholesterol were significantly reduced in the animals treated, both in the normotensive and the hypertensive. High levels of glutamic-pyruvic transaminase and liver humid weight were found in the WT and the ST groups, when compared to their control groups. The findings in our study show that tamoxifentreated female rats presented a lower risk of cardiovascular diseases for the duration of the treatment. Further research might confirm the cardiovascular and renal benefits of tamoxifen therapy in the treatment of breast cancer.