ArticleIndian journal of gastroenterology : official journal of the Indian Society of Gastroenterology2022
Effect of combined farnesoid X receptor agonist and angiotensin II type 1 receptor blocker on ongoing hepatic fibrosis.
Article in Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 10 citations in OpenAlex.
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- Review
- Angelica dahurica extract and its effective component bergapten alleviated hepatic fibrosis by activating FXR signaling pathway.Journal of natural medicines · 2024Article
- Spontaneous Epiretinal Membrane Resolution and Angiotensin Receptor Blockers: Case Observation, Literature Review and Perspectives.Biomedicines · 2023Article
- Editorial commentary on the Indian Journal of Gastroenterology-March-April 2022.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2022Article
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Authors and funding
22 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
objectiveNonalcoholic steatohepatitis (NASH) is difficult to diagnose in patients with no symptoms. We aimed to investigate the combined effect of farnesoid X receptor (FXR) agonist, obeticholic acid (OCA), and angiotensin II type 1 receptor blocker (ARB: losartan) on an ongoing hepatic fibrosis in a NASH rat model.
methodsFischer 344 rats were fed with choline-deficient L-amino-acid-defined (CDAA) diet for 16 weeks. After 8-week administration of CDAA diet, OCA, losartan, or a combination of these drugs was administered at a dose of 30 mg/kg/day for 8 weeks by oral gavage. The in vivo and in vitro effects of OCA + losartan and liver fibrosis progression, lipopolysaccharide (LPS), Toll-like receptor 4 (TLR4) regulatory cascade, and gut barrier function were evaluated.
resultsOCA + losartan alleviated hepatic fibrosis progression by suppressing α-SMA expression. It inhibited the proliferation of activated hepatic stellate cell (Ac-HSC) and mRNA expression of hepatic transforming growth factor-β1 (TGF-β1), TLR4, and tissue inhibitor of metalloproteinase-1 (TIMP-1) and decreased the hydroxyproline levels. OCA increased the hepatic matrix metalloproteinase-2 (MMP-2) mRNA expression. OCA decreased the mRNA expression of hepatic LPS-binding protein and intestinal permeability by ameliorating the disruption of CDAA diet-induced zonula occludens-1. Losartan directly inhibited the proliferation of Ac-HSC. The in vitro suppressive effects of OCA + losartan on the mRNA expressions of TGF-β1 and α1(I)-procollagen, TLR4, and TIMP-1 in Ac-HSCs were almost in parallel.
conclusionsOCA + losartan suppressed the ongoing hepatic fibrosis by attenuating gut barrier dysfunction and suppressing Ac-HSC proliferation. Combined therapy may be a promising novel approach for NASH with fibrosis.
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