Abstract : We previously reported that acetaminophen (APAP)-induced liver injury (AILI) in mice is associated
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Abstract : We previously reported that acetaminophen (APAP)-induced liver injury (AILI) in mice is associated with a rise in serum levels of the glucocorticoid (GC) corticosterone. In the current study we provide evidence that endogenous GC play a pathologic role in AILI. Specifically pretreatment of mice with the GC receptor (GCR) inhibitor RU486 (mifepristrone) protected normal but not adrenalectomized mice from AILI while pretreatment with dexamethasone a synthetic GC exacerbated AILI. RU486 did not affect the depletion of whole liver reduced GSH or the formation of APAP-protein adducts. It also had no effects on the formation of reactive oxygen species or the depletion of mitochondrial GSH or ATP. While RU486 pretreatment also protected against halothane-induced liver injury it exacerbated concanavalin A (ConA)- and carbon tetrachloride (CCl(4))-induced liver injury demonstrating the complexity of GC effects in different types of liver injury. Conclusion These results suggest that under certain conditions elevated levels of GC might represent a previously unappreciated risk factor for liver injury caused by APAP and other drugs through the diverse biological processes regulated by GCR.Published by Elsevier Inc.PMID 20510877 PubMed - indexed for MEDLINEPMCID PMC2897926 Available on 2011/7/1Publication Types MeSH Terms SubstancesPublication Types Research Support N.I.H. ExtramuralResearch Support N.I.H. IntramuralMeSH TermsAcetaminophen/toxicityAnimalsCorticosterone/metabolismDexamethasone/metabolismDrug-Induced Liver Injury/metabolism*Drug-Induced Liver Injury/pathologyFemaleGlucocorticoids/metabolism*Liver/drug effectsLiver/metabolismLiver/pathologyMaleMiceMice Inbred C57BLMifepristone/pharmacologyReceptors Glucocorticoid/antagonists amp inhibitorsStress PhysiologicalSubstancesGlucocorticoidsReceptors GlucocorticoidAcetaminophenDexamethasoneCorticosteroneMifepristoneLinkOut - more resourcesFull Text SourcesElsevier ScienceEBSCOSwets Information ServicesOther Literature SourcesCOS Scholar UniverseMedicalSteroids - MedlinePlus Health InformationMolecular Biology DatabasesRU-486 - HSDBDEXAMETHASONE - HSDBACETAMINOPHEN - HSDB Supplemental Content Related citations Hepatoprotective role of endogenous interleukin-13 in a murine model of acetaminophen-induced liver disease. 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Related articles are displayed in ranked order from most to least relevant with the “linked from” citation displayed first. Compound (MeSH Keyword) PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles. Substance (MeSH Keyword) PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles. Recent activity Clear Turn Off Turn On Pathologic role of stressed-induced glucocorticoids in drug-induced liver injury... Pathologic role of stressed-induced glucocorticoids in drug-induced liver injury in mice.Biochem Biophys Res Commun. 2010 Jul 2 397(3)453-8. Epub 2010 May 27 . PubMed Your browsing activity is empty. Activity recording is turned off. Turn recording back on See more... 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