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The effects of spironolactone in preventing bile duct ligation-induced hepatitis in a rat model

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dc.contributor.authorVELİOĞLU ÖĞÜNÇ, AYLİZ
dc.contributor.authorsÖzer Şehirli A., Kökeş A., Velioğlu-öğünç A., Tetik Ş., Özkan N., Çetinel Ş., Sayıner S., Dülger G.
dc.date.accessioned2022-03-15T02:17:13Z
dc.date.available2022-03-15T02:17:13Z
dc.date.issued2021
dc.description.abstractCholestasis is associated with the accumulation of bile acids and bilirubin in the hepatocytes and leads to liver injury. Pregnane X Receptor (PXR) coordinates protective hepatic responses to toxic stimuli, and this receptor was reported to stimulate bile secretion by increasing MRP2 expression. Since PXR activators were reported to be anti-inflammatory in the liver, PXR was proposed as a drug target for the treatment of chronic inflammatory liver diseases. We investigated the potential protective effect of spironolactone (SPL), an enzyme inducer, in hepatotoxicity induced by bile duct ligation in rats. Wistar Albino (250-300 g) rats were divided into the control group and the bile duct ligated (BDL) group. BDL group was divided into three subgroups; following BDL, for 3 days, the first group received propylene glycol (vehicle of SPL) (blinded), the second subgroup received spironolactone (SPL) (200 mg/kg oral), and the third subgroup received SPL for 3 days, starting 3 days after the bile duct ligation, in order to investigate if it has a healing effect after hepatitis had developed. The control group was sham-operated and received saline. At the end of the experiment, blood and tissue samples were collected. Serum TNF-α, NF-ĸB, bilirubin, IL-6 levels, ALT, AST, ALP activities and tissue MPO activity and oxidant damage increased after the bile duct ligation was significantly decreased following SPL administration. PXR and MRP2 activity showed an increase in the hepatocytes as a result of the treatment. In conclusion, it was observed that SPL administration significantly decreases liver inflammation and damage related to BDL. © 2021, Iranian Journal of Pharmaceutical Research. All rights reserved.
dc.identifier.doi10.22037/ijpr.2020.112488.13786
dc.identifier.issn17350328
dc.identifier.urihttps://hdl.handle.net/11424/248291
dc.language.isoeng
dc.publisherIranian Journal of Pharmaceutical Research
dc.relation.ispartofIranian Journal of Pharmaceutical Research
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectCholestasis
dc.subjectInflammation
dc.subjectMultidrug resistance-associated protein 2
dc.subjectNF-ĸB
dc.subjectPregnanX receptor
dc.subjectSpironolactone
dc.titleThe effects of spironolactone in preventing bile duct ligation-induced hepatitis in a rat model
dc.typearticle
dspace.entity.typePublication
local.avesis.id74239745-bca2-48c9-be67-45b4299929aa
local.import.packageSS21
local.import.sourceScopus
local.indexed.atSCOPUS
local.indexed.atPUBMED
oaire.citation.endPage44
oaire.citation.issue2
oaire.citation.startPage35
oaire.citation.titleIranian Journal of Pharmaceutical Research
oaire.citation.volume20
relation.isAuthorOfPublication13300bf6-ba96-4f87-9868-b0d2c86f572a
relation.isAuthorOfPublication.latestForDiscovery13300bf6-ba96-4f87-9868-b0d2c86f572a

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