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Protective effect of 17β-estradiol on oxidative stress and liver dysfunction in aged male rats

Efecto protector del 17β-estradiol sobre el estrés oxidativo y la disfunción hepática en ratas viejas macho

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Abstract

In aging liver oxidative stress increases due to the decrease in antioxidant bio-molecules such as estrogens which can be modified by hormonal replacement therapy (HRT). With this in mind, we hypothesized that age-related decline in steroidogenesis may be associated with the impairment of the antioxidant defense cells in liver, the increase in lipid peroxidation, hepatic dysfunction and histological changes; estrogens prevent all these changes induced by aging. 17β-estradiol treatment was initiated in 12 month-old Wistar rats, and continued until 18 months of age. Our results showed that 17β-estradiol (E2) level in the serum of the aged untreated rats was reduced by −32% in 18 month-old rats compared to the young animals (4-month-old). The superoxide dismutase (SOD), catalase (CAT), and gluthatione peroxidase (GPX) activities were reduced by −47, −46, and −29% respectively in old rat liver. In addition, the TBARs in liver and hepatic dysfunction parameters in plasma such as gamma-glutamyl transferase (GGT), phosphatase alkalin (PAL) as well as bilirubin level increased significantly in old rats, and histological changes were investigated. In E2-treated rats, protective effects were observed. Indeed, 17β-estradiol attenuates all changes induced by aging. The 17β-estradiol level was higher in old E2-treated rats compared to the control rats. Moreover, the SOD, CAT and GPX activities were higher by +28, +15, and +11% respectively. This anti-aging effect of estrogens was clarified by a lower level of lipid peroxidation and liver dysfunction parameters as well as by histological observation.

Resumen

El estrés oxidativo hepático aumenta con el envejecimiento debido a la disminución de moléculas antioxidantes como los estrógenos, lo que puede ser modificado mediante tratamiento hormonal sustitutorio. Se estudia en este trabajo el efecto del tratamiento a largo plazo con 17β-estradiol (E2) sobre los cambios asociados al envejecimiento hepático. El tratamiento con E2 se inició en ratas de 12 meses y continuó hasta los 18 meses. Los resultados mostraron un descenso del 32% del nivel sérico de E2 en ratas no tratadas respecto de los animales jóvenes (4 meses). La actividad superóxido dismutasa (SOD), catalasa (CAT) y glutatión peroxidasa (GPX) se redujo el 47, 46 y 29% respectivamente en hígado de ratas viejas. En elmismo sentido, aumentaron significativamente parámetros séricos indicativos de disfunción hepática, como la actividad gammaglutamil transferasa, fosfatasa alcalina y el nivel de bilirrubina. El tratamiento con estradiol incrementa la actividad SOD, CAT y GPX y disminuye el nivel de peroxidación lipídica y los parámetros indicativos de disfunción hepática. Los resultados indican que el E2 puede mejorar la disfunción hepática asociada al envejecimiento en ratas macho viejas.

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Correspondence to K. Hamden.

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Hamden, K., Carreau, S., Ellouz, F. et al. Protective effect of 17β-estradiol on oxidative stress and liver dysfunction in aged male rats. J. Physiol. Biochem. 63, 195–201 (2007). https://doi.org/10.1007/BF03165782

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  • DOI: https://doi.org/10.1007/BF03165782

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