Effect of oophorectomy and exogenous estrogen replacement on liver injury in experimental obstructive jaundice

Uçan, Hamdi Bülent; Kaplan, Mehmet; Salman, Bülent; Yılmaz, Utku; Menteş, B. Bülent; Aybay, Cemalettin

doi:10.3748/wjg.14.2818

Cited by 6 publications

(6 citation statements)

References 45 publications

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“…In the HepG2 cells, FXR expression level was not altered by high concentration IL-6 treatment for 24 h, though that was decreased by low concentration of IL-6 treatment for 24 h. These results also suggested that the maintenances mechanism of FXR protein expression level and activity worked as cellular protection when sever inflammation occurred. This suggestion is also confirmed by the fact that intestinal I/R injury was recovered at 24 h (24,27). The PXR protein expression level was recovered at 24 h after intestinal I/R, though PXR mRNA level was still decreased.…”

Section: Discussionsupporting

confidence: 55%

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The Decrease in Farnesoid X Receptor, Pregnane X Receptor and Constitutive Androstane Receptor in the Liver after Intestinal Ischemia-Reperfusion

Ogura¹,

Terada²,

Tsujimoto³

et al. 2012

J Pharm Pharm Sci

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Purpose. Intestinal ischemia-reperfusion (I/R) damages remote organs, including the liver, and promotes multi-organ failure (MOF). However, the molecular mechanisms underlying acute liver injury after intestinal I/R have not been completely elucidated. Farnesoid X receptor (FXR), pregnane X receptor (PXR) and constitutive androstane receptor (CAR) regulate metabolizing enzymes and transporters, and coordinately prevent hepatotoxicity reflecting an inability of appropriate excretion of endogenous toxic compounds. In this study, we assessed FXR, PXR and CAR expression levels and their localization levels in nuclei in the liver after intestinal I/R. We also investigated the effect of IL-6 on FXR, PXR and CAR expression levels and their localization levels in nuclei in in vitro experiments. Methods. We used intestinal I/R model rats. Moreover, HepG2 cells were used in in vitro study. Real-time PCR and Western blotting were used to assess mRNA and protein expression levels. Nuclear receptor localization in nuclei was analyzed by Western blotting using nuclear extracts. Results. FXR and PXR expression levels began to be decreased at 3 h, and FXR, PXR and CAR expression levels were decreased at 6 h after intestinal I/R. The localization levels of FXR, PXR and CAR in nuclei began to be decreased at 3 h, and all of them were decreased at 6 h after intestinal I/R. In HepG2 cells, FXR, PXR and CAR expression levels were decreased by 0.5-1 ng/mL, 0.5-100 ng/mL and 100 ng/mL IL-6 treatment for 24 h, respectively. FXR, PXR and CAR localization levels in nuclei were suppressed by 0.5-10 ng/mL, 10-100 ng/mL and 10-100 ng/mL IL-6 treatment for 24 h, respectively. Conclusions. FXR, PXR and CAR expression levels are decreased in the liver after intestinal I/R. IL-6 is one of main causes the decreases in expressions of these receptors. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Section: Discussionsupporting

confidence: 55%

“…Measurement of IL-6 level in the liver was carried out as described in a previous report with some modification (27). For the measurement, the liver tissue was homogenized in PBS containing 2 mM PMSF, 5 µg/mL pepstatin and 5 µg/mL leupeptin.…”

Section: Measurement Of Il-6 Level In the Livermentioning

confidence: 99%

The Decrease in Farnesoid X Receptor, Pregnane X Receptor and Constitutive Androstane Receptor in the Liver after Intestinal Ischemia-Reperfusion

Ogura¹,

Terada²,

Tsujimoto³

et al. 2012

J Pharm Pharm Sci

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“…In the present study, oral ET tended to increase IL-6 level, but IL-6 in the transdermal ET group did not change. It has been reported that IL-6 is synthesized by Kupffer cells in the liver (28). Therefore, increase in IL-6 by oral ET might be due to first-pass hepatic metabolism.…”

Section: Discussionmentioning

confidence: 99%

Effects of oral and transdermal estrogen therapies on circulating cytokines and chemokines in postmenopausal women with hysterectomy

Saijo¹,

Uemura²,

Matsuzaki³

et al. 2009

European Journal of Endocrinology

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Objective: The aim of the present study was to determine the different effects of oral estrogen therapy (ET) and transdermal ET on changes in circulating levels of cytokines and chemokines in relationship to changes in markers of inflammation in postmenopausal women with hysterectomy. Methods: Fifty-five postmenopausal women with hysterectomy were randomly assigned in open, parallel-group fashion to an oral ET group and a transdermal ET group. Serum levels of cytokines and chemokines were simultaneously measured using a multiplexed human cytokine assay. Serum concentrations of high-sensitive C-reactive protein, soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, and E-selectin were measured as vascular inflammation markers. Results: Both oral ET and transdermal ET significantly decreased serum interleukin (IL)-7 concentrations at 12 months (PZ0.020 and PZ0.015 respectively). Transdermal ET decreased serum concentrations of IL-8, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-1b (PZ0.05, PZ0.019, and PZ0.029), but oral ET increased IL-8 level (PZ0.025). There were significant differences in percentage changes in IL-8 and MIP-1b between the oral and transdermal ET groups. Oral ET significantly decreased E-selectin level after 12 months. Conclusion: Transdermal ET reduces circulating levels of IL-8, MCP-1, and MIP-1b, while both oral ET and transdermal ET reduce circulating level of IL-7.

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“…Therefore, sex hormones are immunomodulatory steroids since they regulate the levels of both pro-inflammatory and anti-inflammatory cytokines, mediating the immune response in several reproductive processes and diverse diseases [10,85,87,90,91,92]. There are some reports dealing with the immunomodulatory effects of OC in liver damage or chronic diseases [93,94]. For instance, OC elicited effects on plasma and hepatic cytokines in rats, emulating the possible events in normal or cholestatic premenopausal women who are administered OC chronically [12].…”

Section: Female Sex Hormones Oral Contraceptives and Phytoestrogensmentioning

confidence: 99%

“…Also, the effects of estrogens on chronic biliary damage and regeneration have been studied in rats. They were associated with the cytokine production of hepatic IFN-γ and IL-6, which are simulated postmenopausal or oophorectomized women with or without estrogen replacement therapy [93]. Herein, E2 impaired liver functions, in a dual way accelerated both liver damage and healing, as well as significantly changed the cytokine milieu in the cholestatic liver.…”

Section: Female Sex Hormones Oral Contraceptives and Phytoestrogensmentioning

confidence: 99%

Beneficial and Deleterious Effects of Female Sex Hormones, Oral Contraceptives, and Phytoestrogens by Immunomodulation on the Liver

Soria-Jasso

Cariño-Cortés

Muñoz-Pérez

et al. 2019

IJMS

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The liver is considered the laboratory of the human body because of its many metabolic processes. It accomplishes diverse activities as a mixed gland and is in continuous cross-talk with the endocrine system. Not only do hormones from the gastrointestinal tract that participate in digestion regulate the liver functions, but the sex hormones also exert a strong influence on this sexually dimorphic organ, via their receptors expressed in liver, in both health and disease. Besides, the liver modifies the actions of sex hormones through their metabolism and transport proteins. Given the anatomical position and physiological importance of liver, this organ is evidenced as an immune vigilante that mediates the systemic immune response, and, in turn, the immune system regulates the hepatic functions. Such feedback is performed by cytokines. Pro-inflammatory and anti-inflammatory cytokines are strongly involved in hepatic homeostasis and in pathological states; indeed, female sex hormones, oral contraceptives, and phytoestrogens have immunomodulatory effects in the liver and the whole organism. To analyze the complex and interesting beneficial or deleterious effects of these drugs by their immunomodulatory actions in the liver can provide the basis for either their pharmacological use in therapeutic treatments or to avoid their intake in some diseases.

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Effect of oophorectomy and exogenous estrogen replacement on liver injury in experimental obstructive jaundice

Abstract: Our study indicates that E2 impaired liver functions, accelerated both the liver damage and healing. In the conditions of bile duct obstruction, estrogen significantly changed the cytokine milieu in the liver.

Cited by 6 publications

References 45 publications

The Decrease in Farnesoid X Receptor, Pregnane X Receptor and Constitutive Androstane Receptor in the Liver after Intestinal Ischemia-Reperfusion

The Decrease in Farnesoid X Receptor, Pregnane X Receptor and Constitutive Androstane Receptor in the Liver after Intestinal Ischemia-Reperfusion

Effects of oral and transdermal estrogen therapies on circulating cytokines and chemokines in postmenopausal women with hysterectomy

Beneficial and Deleterious Effects of Female Sex Hormones, Oral Contraceptives, and Phytoestrogens by Immunomodulation on the Liver

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