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THE LIVER REDOX STATUS IN AN ANIMAL MODEL OF ESTROGEN DEFICIENCY ASSOCIATED WITH RENOVASCULAR HYPERTENSION AND THE BENEFICIAL EFFECTS OF TIBOLONE
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Speaker:
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Clairce Salgueiro-Pagadigorria
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Author:
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E.H. Gilglioni1, L.B. Campos1, C.R. Ambiel1, M.N. Brito1, R.F. Garcia1, E.L. Ishii-Iwamoto2, C.L. Salgueiro-Pagadigorria1*
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Affiliation:
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1Physiological Sciences, 2Biochemistry, University of Maringa, Maringa, Brazil. *clspagadigorria@uem.br
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Aims and background: Hypertension is a frequent condition in post-menopausal women. This work was planned to evaluate the liver redox status in an animal model of oestrogen deficiency associated with renovascular hypertension (two-kidneys, one clip, 2K1C), and the possibility of beneficial effects of tibolone, a drug that has been suggested to be effective in treating many menopause symptoms.
Methods: Ovariectomized hypertensive (OVX + 2K1C) Wistar rats were used in this study. The results were compared to those obtained with ovariectomized (OVX) and control (sham-operated) rats. Three weeks after the surgical procedures, rats of OVX + 2K1C group received daily doses of tibolone (0.04 mg/kg - OVX + 2K1CT rats) or vehicle (OVX + 2K1C), over a period of 15 days. Thereafter, the rats were anaesthetized for direct blood pressure measurements and liver removal. The liver redox status was evaluated through measurements of reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS) contents, as well as the activities of five antioxidants enzymes and the mitochondrial reactive oxygen species (ROS) generation were evaluated.
Results: OVX + 2K1C rats presented mean blood pressure significantly higher (+28%), as compared to control and OVX rats. The treatment with tibolone (OVX + 2K1CT) reduced the blood pressures to values close to ones found in control and OVX rats. The livers content of GSH was increased and of TBARS was decreased in the same group of animals (OVX + 2K1CT) as compared with all other groups. The rates of mitochondrial ROS generation, which were increased in OVX + 2K1C rats (+52%), decreased in OVX + 2K1CT rats to values similar to those found in control and OVX rats. Among the antioxidant enzymes studied, stand out the beneficial effect of tibolone on the glucose-6-phosphate dehydrogenase activity, which was significantly reduced in OVX and OVX + 2K1C rats, and was reestablished in OVX + 2K1CT to values similar to control rats.
Conclusion: Tibolone was effective in reducing the mean blood pressure in OVX + 2K1CT rats and this effect was accompanied of beneficial effects on liver redox status.
Acknowledgements: This work was supported by Fundação Araucária and grants from CNPq.
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