engleski

The role of 17 Beta-estradiol in the regulation of antioxidant enzymes via the nrf2-keap1 pathway in livers of CBA/H mice

We aimed to explore the impact of surgical estrogen (E2) deprivation/administration on the antioxidant enzymes expression with the emphasis on alteration of NF-E2-related factor 2/Kelchlike ECH-associated protein 1 (Nrf2/Keap1) pathway in physiological conditions in liver of CBA/H mice of both sexes. Hepatic oxidative stress markers were determined by measuring lipid peroxidation and DNA damage by comet assay method. The expression and activities of two isoforms of Superoxide dismutase (Sod-1, Sod-2) and Catalase (Cat) were studied by real-time PCR, western blot and spectrophotometrical analysis. The effect of E2 on the Nrf/Keap1 protein level and localisation was assessed using cytosolic and nuclear fractions. We showed E2-mediated repression of antioxidant enzymes Sod-1, Sod-2 and Cat in the liver of ovariectomized mice treated with E2, and its association with the decreased level of Nrf2/Keap1 proteins in the nucleus. We have observed beneficial effects of long-term E2 administration on lipid peroxidation (LPO), but not on the DNA damage in the liver of ovariectomized mice. The results from this study may additionally confirm the protective ability of E2 in prolonging the onset of age-related disease in females and finally contribute to their longer lifespan.

estrogen; sex-related; ROS; Nrf2; Keap1; Sod-1; Sod-2; Cat

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