ArticleBritish journal of pharmacology2018
The selective mineralocorticoid receptor antagonist eplerenone prevents decompensation of the liver in cirrhosis.
Article in British journal of pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Unveiling the role of aldosterone in metabolic dysfunction-associated steatotic liver disease.Reviews in endocrine & metabolic disorders · 2026Review
- Mineralocorticoid Receptor Antagonists for Liver Fibrosis: Potential Mechanisms and Research Progress.Journal of clinical and translational hepatology · 2026Review
- Therapeutic Targets for Hepatic Fibrosis Driven by Hypoxia-Mediated Hepatic Stellate Cell Activation.Biomolecules · 2026Review
- Eplerenone, a mineralocorticoid receptor inhibitor, reduces cirrhosis associated changes of hepatocyte glucose and lipid metabolism.Cell communication and signaling : CCS · 2024Article
- Autophagic degradation of MVBs in LSECs promotes Aldosterone induced-HSCs activation.Hepatology international · 2024Article
- Development of novel liver-targeting glucocorticoid prodrugs.Medicine in drug discovery · 2024Article
- Maternal hepatic immunology during pregnancy.Frontiers in immunology · 2023Review
- Narrative Review: Glucocorticoids in Alcoholic Hepatitis-Benefits, Side Effects, and Mechanisms.Journal of xenobiotics · 2022Review
- Review
- Identification of a Potential miRNA-mRNA Regulatory Network Associated With the Prognosis of HBV-ACLF.Frontiers in molecular biosciences · 2021Article
- The selective mineralocorticoid receptor antagonist eplerenone prevents decompensation of the liver in cirrhosis.British journal of pharmacology · 2018Article
- The expanding class of mineralocorticoid receptor modulators: New ligands for kidney, cardiac, vascular, systemic and behavioral selective actions.Acta endocrinologica (Bucharest, Romania : 2005)Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe mineralocorticoid receptor (MR) contributes to fibrosis in various tissues, and MR antagonists, like eplerenone, are used to prevent fibrosis. The role of MR antagonists in hepatic fibrosis and cirrhosis is unknown. Here, we investigated the role of MRs and eplerenone in cirrhosis development. EXPERIMENTAL APPROACH: Liver fibrosis (5 weeks) and cirrhosis, without (8 weeks) and with ascites (12 weeks), were induced by CCl KEY
resultsIn cirrhosis with ascites, MR mRNA and protein expressions were reduced in hepatocytes of hypoxic areas. While in normoxic areas MRs were mainly cytosolic, the remaining MRs in hypoxic areas were mainly localized in the nuclei, indicating activation followed by translocation and degradation. Accordingly, eplerenone treatment prevented nuclear MR translocation and the worsening of cirrhosis. Exposing hepatocytes ex vivo to hypoxia induced nuclear MR translocation and enhanced transcriptional MR activity at response elements of the NF-κB pathway. CONCLUSIONS AND IMPLICATIONS: We showed for the first time that hypoxia leads to a pathogenetic ligand-independent activation of hepatic MRs during cirrhosis resulting in their nuclear translocation and transcriptional activation of the NF-κB pathway. Treatment with eplerenone prevented the worsening of cirrhosis by blocking this ligand-independent activation of the MR.
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