Estradiol affects liver mitochondrial function in ovariectomized and tamoxifen-treated ovariectomized female rats

Moreira, Paula I.; Custódio, José B.A.; Nunes, Elsa; Moreno, António J.; Seiça, Raquel; Oliveira, Catarina R.; Santos, Maria S.

doi:10.1016/j.taap.2007.02.006

Cited by 21 publications

(24 citation statements)

References 56 publications

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“…Although accumulating evidence indicates that 17 β estradiol can modulate the mitochondrial function in different cell lines [28], the direct evaluation of changes of membrane potential in Huh7.5 has not yet been fully examined. Furthermore, in vivo studies have shown negative effects of exogenous 17 β estradiol on mitochondria of ovariectomized rats [29]. Also the results obtained with genistein are quite new and in disagreement with previous ones.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Oxidative Stress by 17 β-Estradiol and Genistein in Human Hepatic Cell Lines In Vitro

Surico¹,

Ercoli²,

Farruggio

et al. 2017

Cell Physiol Biochem

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Background/Aims: estrogens and phytoestrogens exert hepatoprotection through mechanisms not clearly examined yet. Here, we investigated the protective effects exerted by 17β-estradiol and genistein against oxidative stress in hepatocytes and hepatic stellate cells (HSCs) and the involvement of specific receptors and the intracellular signalling. Methods: Huh7.5 and LX-2, alone or in co-culture with Huh7.5, were treated with 17β-estradiol and genistein alone or in the presence of menadione and of estrogen receptors (ERs) and G protein-coupled-estrogenic-receptors (GPER) blockers. Cell viability, mitochondrial membrane potential and oxidant/antioxidant system were measured by specific kits. Western Blot was used for the analysis of Akt and p38-mitogen-activated-protein kinases (MAPK) activation and α-smooth-muscle actin expression. Results: In Huh7.5, 17β-estradiol and genistein prevented the effects of peroxidation by modulating Akt and p38MAPK activation. Similar antioxidant and protective findings were obtained in LX-2 of co-culture experiments, only. ERs and GPER blockers were able to prevent the effects of 17β-estradiol and genistein. Conclusion: In Huh7.5 and LX-2, 17β-estradiol and genistein counteract the effects of peroxidation through the involvement of ERs and GPER and by an intracellular signalling related to Akt and p38MAPK. As concerning LX-2, paracrine factors released by Huh7.5 play a key role in protection against oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Modulation of Oxidative Stress by 17 β-Estradiol and Genistein in Human Hepatic Cell Lines In Vitro

Surico¹,

Ercoli²,

Farruggio

et al. 2017

Cell Physiol Biochem

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“…It is well established that tamoxifen competitively binds to ERs on tumors and other tissue targets, producing a nuclear complex that inhibits estrogen effects. Specifically, the ER/tamoxifen complex recruits corepressors to stop genes being switched on by estrogens (43,46), a fact that may explain, at least in part, the suppressive effect of tamoxifen on Cyp2e1 regulation. The tamoxifeninduced repression in Cyp2e1 may also be attributed to the lower serum progesterone levels detected in drug-treated mice compared with controls.…”

Section: Discussionmentioning

confidence: 99%

“…The role of estrogens was also evaluated in intact cyclic females treated with tamoxifen, a drug with antiestrogenic effects in the breast tissue that is used as standard endocrine treatment in women with hormone receptorpositive breast cancer. Tamoxifen, though, under certain circumstances, can also exert estrogenic agonist properties depending on the tissue (46). In addition, the hepatic Cyp2e1 expression pattern was assessed at the four distinct phases of the estrous cycle of intact cyclic female mice and compared with the male Cyp2e1 expression profile.…”

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confidence: 99%

Sex steroid hormones regulate constitutive expression ofCyp2e1in female mouse liver

Konstandi

Cheng

Gonzalez

2013

American Journal of Physiology-Endocrinology and Metabolism

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Konstandi M, Cheng J, Gonzalez FJ. Sex steroid hormones regulate constitutive expression of Cyp2e1 in female mouse liver. Am J Physiol Endocrinol Metab 304: E1118 -E1128, 2013. First published April 2, 2013; doi:10.1152/ajpendo.00585.2012.-CYP2E1 is of paramount toxicological significance because it metabolically activates a large number of low-molecular-weight toxicants and carcinogens. In this context, factors that interfere with Cyp2e1 regulation may critically affect xenobiotic toxicity and carcinogenicity. The aim of this study was to investigate the role of female steroid hormones in the regulation of CYP2E1, as estrogens and progesterone are the bases of contraceptives and hormonal replacement therapy in menopausal women. Interestingly, a fluctuation in the hepatic expression pattern of Cyp2e1 was revealed in the different phases of the estrous cycle of female mice, with higher Cyp2e1 expression at estrus (E) and lower at methestrus (ME), highly correlated with that in plasma gonadal hormone levels. Depletion of sex steroids by ovariectomy repressed Cyp2e1 expression to levels similar to those detected in males and cyclic females at ME. Hormonal supplementation brought Cyp2e1 expression back to levels detected at E. The role of progesterone appeared to be more prominent than that of 17␤-estradiol. Progesterone-induced Cyp2e1 upregulation could be attributed to inactivation of the insulin/PI3K/Akt/FOXO1 signaling pathway. Tamoxifen, an anti-estrogen, repressed Cyp2e1 expression potentially via activation of the PI3K/Akt/FOXO1 and GH/STAT5b-linked pathways. The sex steroid hormone-related changes in hepatic Cyp2e1 expression were highly correlated with those observed in Hnf-1␣, ␤-catenin, and Srebp-1c. In conclusion, female steroid hormones are clearly involved in the regulation of CYP2E1, thus affecting the metabolism of a plethora of toxicants and carcinogenic agents, conditions that may trigger several pathologies or exacerbate the outcomes of various pathophysiological states.Cyp2e1; 17␤-estradiol; progesterone; estrous cycle; mice PITUITARY HORMONES, in particular, growth hormone (GH), are considered critical in Cyp2e1 regulation. Previous studies revealed that pituitary hormone depletion by hypophysectomy resulted in Cyp2e1 upregulation in the liver of rats and GH supplementation normalized Cyp2e1 expression to constitutive levels by suppressing Cyp2e1 transcription (11,28,70,71,80). It is of interest to note that sex steroid hormones target complex regulatory dynamics including GH secretion. On the one hand, they augment GH-secretory burst by amplifying feedforward [via both GH-releasing hormone, GH-releasing peptide(s)] and on the other hand they attenuate feedback (imposed by somatostatin and GH). The role of testosterone is less clear (49,67). Previous studies in humans and experimental animals presented contradictory findings regarding sex differentiation in CYP2E1 constitutive expression and the role of sex steroid hormones in this regulation (5,11,29,33,34,59). This contradiction is probably du...

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“…Postmenopausal depletion of endogenous estrogens may contribute to tissue injury and apoptosis via induced oxidative stress (Dilek et al 2010;Lamas et al 2015). It has been shown that a reduction in 17β-estradiol (E2) leads to an increase in oxidative stress in the body, which is dependent on the concentration and chemical structure of this hormone (Moreira et al 2007;Dilek et al 2010;Moreira et al 2011). Furthermore, it has been shown that postmenopausal women, compared with premenopausal women, have higher serum concentrations of oxidative stress markers including oxidized GSH and lipid peroxidation (Doshi and Agarwal 2013).…”

Section: Introductionmentioning

confidence: 99%

Raloxifene and Tamoxifen Reduce PARP Activity, Cytokine and Oxidative Stress Levels in the Brain and Blood of Ovariectomized Rats

Yazğan

Nazıroğlu

2016

J Mol Neurosci

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It is well known that 17β-estradiol (E2) has an antioxidant role on neurological systems in the brain. Raloxifene (RLX) and tamoxifen (TMX) are selective estrogen receptor modulators. An E2 deficiency stimulates mitochondrial functions for promoting apoptosis and increasing reactive oxygen species (ROS) production. However, RLX and TMX may reduce the mitochondrial ROS production via their antioxidant properties in the brain and erythrocytes of ovariectomized (OVX) rats. We aimed to investigate the effects of E2, RLX, and TMX on oxidative stress, apoptosis, and cytokine production in the brain and erythrocytes of OVX rats.Forty female rats were divided into five groups. The first group was used as a control group. The second group was the OVX group. The third, fourth, and fifth groups were OVX + E2, OVX + TMX, and OVX + RLX groups, respectively. E2, TMX, and RLX were given subcutaneously to the OVX + E2 and OVX + TMX, OVX + RLX groups for 14 days after the ovariectomy respectively.While brain and erythrocyte lipid peroxidation levels were high in the OVX group, they were low in the OVX + E2, OVX + RLX, and OVX + TMX groups. OVX + E2, OVX + RLX, and OVX + TMX treatments increased the lowered glutathione peroxidase activity in erythrocytes and the brain and reduced glutathione and vitamin E concentrations in the brain. β-carotene and vitamin A concentrations in the brain and TNF-α and interleukin (IL)-1β levels in the plasma of the five groups were not significantly changed by the treatments. However, increased plasma IL-4 levels and Western blot results for brain poly (ADP-ribose) polymerase (PARP) in the OVX groups were decreased by E2, TMX, and RLX treatments, although proapoptotic procaspase 3 and 9 activities were increased by the treatments.In conclusion, we observed that E2, RLX, and TMX administrations were beneficial on oxidative stress, inflammation, and PARP levels in the serum and brain of OVX rats by modulating antioxidant systems, DNA damage, and cytokine production.

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Estradiol affects liver mitochondrial function in ovariectomized and tamoxifen-treated ovariectomized female rats

Cited by 21 publications

References 56 publications

Modulation of Oxidative Stress by 17 β-Estradiol and Genistein in Human Hepatic Cell Lines In Vitro

Modulation of Oxidative Stress by 17 β-Estradiol and Genistein in Human Hepatic Cell Lines In Vitro

Sex steroid hormones regulate constitutive expression ofCyp2e1in female mouse liver

Raloxifene and Tamoxifen Reduce PARP Activity, Cytokine and Oxidative Stress Levels in the Brain and Blood of Ovariectomized Rats

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