2024
PPAR-Mediated Bile Acid Glucuronidation: Therapeutic Targets for the Treatment of Cholestatic Liver Diseases
Gallucci G, Hayes C, Boyer J, Barbier O, Assis D, Ghonem N. PPAR-Mediated Bile Acid Glucuronidation: Therapeutic Targets for the Treatment of Cholestatic Liver Diseases. Cells 2024, 13: 1296. PMID: 39120326, PMCID: PMC11312002, DOI: 10.3390/cells13151296.Peer-Reviewed Original ResearchPrimary biliary cholangitisPrimary sclerosing cholangitisPeroxisome proliferator-activated receptorCholestatic liver diseaseUrsodeoxycholic acidUridine 5'-diphospho-glucuronosyltransferaseObeticholic acidBile acid metabolismAdjunctive therapyIncomplete response to UDCAProgression of primary biliary cholangitisResponse to UDCALiver diseasePeroxisome proliferator-activated receptor agonistsSecond-line treatmentMarkers of cholestasisImpairment of bile flowTherapeutic targetTreatment of cholestatic liver diseasesRetention of bile acidsAlternative treatment strategiesProgression to fibrosisProliferator-activated receptorsAcid metabolismBiliary cholangitis
2017
Combination Therapy of All-Trans Retinoic Acid With Ursodeoxycholic Acid in Patients With Primary Sclerosing Cholangitis
Assis DN, Abdelghany O, Cai SY, Gossard AA, Eaton JE, Keach JC, Deng Y, Setchell KD, Ciarleglio M, Lindor KD, Boyer JL. Combination Therapy of All-Trans Retinoic Acid With Ursodeoxycholic Acid in Patients With Primary Sclerosing Cholangitis. Journal Of Clinical Gastroenterology 2017, 51: e11-e16. PMID: 27428727, PMCID: PMC5218875, DOI: 10.1097/mcg.0000000000000591.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAlanine TransaminaseAlkaline PhosphataseBile Acids and SaltsCholagogues and CholereticsCholangitis, SclerosingCholestenonesDrug Therapy, CombinationFemaleHumansLiverLiver Function TestsMaleMiddle AgedPilot ProjectsTreatment OutcomeTretinoinUrsodeoxycholic AcidYoung AdultConceptsPrimary sclerosing cholangitisUrsodeoxycholic acidAlanine aminotransferaseUDCA monotherapyPrimary endpointSclerosing cholangitisMedian serum alanine aminotransferasePilot studyWeeks of therapyMarkers of inflammationSerum alanine aminotransferaseRetinoic acidAlkaline phosphataseAll-Trans Retinoic AcidSerum ALP levelsHuman pilot studyCombination of ATRAAddition of ATRABile acid synthesisTrans retinoic acidExploratory pilot studyALT levelsAccepted therapyWeek 12C4 levels
2015
Fibrates and cholestasis
Ghonem NS, Assis DN, Boyer JL. Fibrates and cholestasis. Hepatology 2015, 62: 635-643. PMID: 25678132, PMCID: PMC4515188, DOI: 10.1002/hep.27744.BooksConceptsPrimary sclerosing cholangitisPrimary biliary cirrhosisCholestatic liver diseaseUDCA therapyLiver diseaseUrsodeoxycholic acidNuclear receptorsProgression of PBCHepatic transportersPeroxisome proliferator-activated receptor alphaProliferator-activated receptor alphaToxic bile constituentsApical sodium-dependent bile salt transporterOnly therapeutic optionCholestatic liver disordersBile acid homeostasisBile acid synthesisBile salt transportersMultidrug resistance protein 3Cytochrome P450PPARα effectLiver transplantationSclerosing cholangitisBiliary cirrhosisLiver failure
2010
Combination of retinoic acid and ursodeoxycholic acid attenuates liver injury in bile duct–ligated rats and human hepatic cells
He H, Mennone A, Boyer JL, Cai S. Combination of retinoic acid and ursodeoxycholic acid attenuates liver injury in bile duct–ligated rats and human hepatic cells. Hepatology 2010, 53: 548-557. PMID: 21274875, PMCID: PMC3069505, DOI: 10.1002/hep.24047.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile Acids and SaltsBile DuctsCell ProliferationCells, CulturedCholestasis, IntrahepaticCholesterol 7-alpha-HydroxylaseCollagen Type ICollagen Type I, alpha 1 ChainDisease Models, AnimalHepatocytesHumansLigationLiverMaleMatrix Metalloproteinase 2RatsRats, Sprague-DawleySmad2 ProteinTretinoinUrsodeoxycholic AcidConceptsBile duct ligationBile salt pool sizeLX-2 cellsUrsodeoxycholic acidHepatic stellate cellsRetinoic acidLiver fibrosisStellate cellsPhosphate-buffered salineCommon bile duct ligationMale Sprague-Dawley ratsPrimary human hepatic stellate cellsTumor necrosis factor αBile duct-ligated ratsHuman hepatic stellate cellsBile duct proliferationHuman hepatocytesLiver hydroxyproline contentNecrosis factor αSprague-Dawley ratsAcute promyelocytic leukemiaΑ-SMA expressionDuct-ligated ratsSmooth muscle actinMatrix metalloproteinase-2
2007
Clinical trial: modulation of human placental multidrug resistance proteins in cholestasis of pregnancy by ursodeoxycholic acid
AZZAROLI F, MENNONE A, FELETTI V, SIMONI P, BAGLIVO E, MONTAGNANI M, RIZZO N, PELUSI G, DE ALOYSIO D, LODATO F, FESTI D, COLECCHIA A, RODA E, BOYER J, MAZZELLA G. Clinical trial: modulation of human placental multidrug resistance proteins in cholestasis of pregnancy by ursodeoxycholic acid. Alimentary Pharmacology & Therapeutics 2007, 26: 1139-1146. PMID: 17894656, DOI: 10.1111/j.1365-2036.2007.03462.x.Peer-Reviewed Original ResearchConceptsUrsodeoxycholic acid administrationBile acid levelsUrsodeoxycholic acidBile acidsAcid administrationIntrahepatic cholestasisCord bloodMaternal serum bile acidsCord blood bilirubinAcid levelsRNA expressionCholestasis of pregnancySerum bile acidsTotal bile acidsMRP3 protein expressionPregnancy patientsPhysiological pregnancyPregnant womenMultidrug resistance proteinBlood bilirubinMRP2 expressionMRP4 expressionCholestasisMultidrug resistancePregnancy
1999
The effect of ursodeoxycholic acid on the florid duct lesion of primary biliary cirrhosis
Combes B, Markin R, Wheeler D, Rubin R, West A, Mills A, Eigenbrodt E, Maddrey W, Munoz S, Garcia‐Tsao G, Bonner G, Boyer J, Luketic V, Shiffman M, Peters M, White H, Zetterman R, Carithers R. The effect of ursodeoxycholic acid on the florid duct lesion of primary biliary cirrhosis. Hepatology 1999, 30: 602-605. PMID: 10462363, PMCID: PMC3935822, DOI: 10.1002/hep.510300315.Peer-Reviewed Original ResearchConceptsFlorid duct lesionsPrimary biliary cirrhosisBile duct destructionDuct lesionsUrsodeoxycholic acidDuct destructionBiliary cirrhosisPlacebo-controlled trialNeedle biopsy specimensUDCA patientsAdvanced diseasePlacebo medicationEarly diseaseBiopsy specimensPatientsLesionsBeneficial effectsPathology literaturePrevalenceCirrhosisPlaceboMedicationsDiseaseYearsHepatopathologistBiliary bile acids in primary biliary cirrhosis: Effect of ursodeoxycholic acid
Combes B, Carithers R, Maddrey W, Munoz S, Garcia‐Tsao G, Bonner G, Boyer J, Luketic V, Shiffman M, Peters M, White H, Zetterman R, Risser R, Rossi S, Hofmann A. Biliary bile acids in primary biliary cirrhosis: Effect of ursodeoxycholic acid. Hepatology 1999, 29: 1649-1654. PMID: 10347103, PMCID: PMC4004074, DOI: 10.1002/hep.510290618.Peer-Reviewed Original ResearchMeSH KeywordsBileBile Acids and SaltsChenodeoxycholic AcidCholic AcidChromatography, GasChromatography, High Pressure LiquidDeoxycholic AcidDouble-Blind MethodDrug Administration ScheduleFemaleHumansLithocholic AcidLiver Cirrhosis, BiliaryMaleMiddle AgedPlacebosRegression AnalysisReproducibility of ResultsTime FactorsUrsodeoxycholic AcidConceptsPrimary biliary cirrhosisBile acid compositionUrsodeoxycholic acidBile acidsBiliary cirrhosisSeverity of PBCSingle bedtime dosePlacebo-controlled trialBiliary bile acidsEndogenous bile acidsMajor bile acidsBedtime dosePlacebo medicationDuodenal bileHigh-pressure liquid chromatography methodPatientsNormal personsBileSignificant decreaseCirrhosisAcid compositionCDCATaurineLiquid chromatography methodYears
1995
A randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid in primary biliary cirrhosis
Combes B, Carithers R, Maddrey W, Lin D, Mcdonald M, Wheeler D, Eigenbrodt E, Muñoz S, Rubin R, Garcia-tsao G, Bonner G, West A, Boyer J, Luketic V, Shiffman M, Mills A, Peters M, White H, Zetterman R, Rossi S, Hofmann A, Markin R. A randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology 1995, 22: 759-766. DOI: 10.1016/0270-9139(95)90294-5.Peer-Reviewed Original ResearchPrimary biliary cirrhosisSerum bilirubinBiliary cirrhosisMajor complicationsStratum 1Liver diseaseTreatment failureAdvanced primary biliary cirrhosisPlacebo-treated patientsPlacebo-controlled trialBile acid poolStratum 3Advanced diseaseLiver histologyPrognostic factorsMilder diseaseSingle doseUrsodeoxycholic acidUrsodiolSevere symptomsPatientsPlaceboLaboratory testsComplicationsBilirubinA randomized, double‐blind, placebo‐controlled trial of ursodeoxycholic acid in primary biliary cirrhosis
Combes B, Carithers R, Maddrey W, Lin D, McDonald M, Wheeler D, Eigenbrodt E, Muñoz S, Rubin R, Garcia‐Tsao G, Bonner G, West A, Boyer J, Luketic V, Shiffman M, Mills A, Peters M, White H, Zetterman R, Rossi S, Hofmann A, Markin R. A randomized, double‐blind, placebo‐controlled trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology 1995, 22: 759-766. PMID: 7657280, DOI: 10.1002/hep.1840220311.Peer-Reviewed Original ResearchConceptsPrimary biliary cirrhosisSerum bilirubinBiliary cirrhosisStratum 1Advanced primary biliary cirrhosisPlacebo-controlled trialBile acid poolLiver histologyPrognostic factorsTreatment failureSingle doseUrsodeoxycholic acidSevere symptomsPatientsUrsodiolLaboratory testsPlaceboHistologyBilirubinCirrhosisBiochemical testsGood responseStratum 3Acid poolLess effect
1994
Expression and characterization of a functional rat liver Na+ bile acid cotransport system in COS-7 cells
Boyer J, Ng O, Ananthanarayanan M, Hofmann A, Schteingart C, Hagenbuch B, Stieger B, Meier P. Expression and characterization of a functional rat liver Na+ bile acid cotransport system in COS-7 cells. American Journal Of Physiology 1994, 266: g382-g387. PMID: 8166278, DOI: 10.1152/ajpgi.1994.266.3.g382.Peer-Reviewed Original ResearchConceptsCOS-7 cellsCotransport systemBile acid transporterUrsodeoxycholic acidTaurochenodeoxycholic acidAcid cotransport systemTauroursodeoxycholic acidBile acidsRat hepatocytesAbsence of sodiumChenodeoxycholic acidCOS cellsEmpty plasmidPMAMneo vectorCholic acidBile acid cotransporterMicroM bilirubinRat liverEvidence of expressionCell linesAcid transportersPosttranslational factorsProgressive uptakeCotransporterAcid cotransporter
1993
Effect of ursodeoxycholic acid on intracellular pH regulation in isolated rat bile duct epithelial cells
Alvaro D, Mennone A, Boyer J. Effect of ursodeoxycholic acid on intracellular pH regulation in isolated rat bile duct epithelial cells. American Journal Of Physiology 1993, 265: g783-g791. PMID: 8238362, DOI: 10.1152/ajpgi.1993.265.4.g783.Peer-Reviewed Original ResearchConceptsBile duct epithelial cellsUrsodeoxycholic acidDuct epithelial cellsBDE cellsHCO3- excretionEffect of UDCAEpithelial cellsHCO3- exchangeCholic acidKrebs-Ringer bicarbonateUDCA infusionUDCA withdrawalRat bile duct epithelial cellsKRB mediumHCO3- symportNormal rat liverIntracellular pH regulationHCO3- secretionSodium tauroursodeoxycholateSecondary activationBasal levelsPresence of HCO3TauroursodeoxycholateRat liverHypercholeresis
1991
Effect of UDCA on intracellular and biliary pH in isolated rat hepatocyte couplets and perfused livers
Strazzabosco M, Sakisaka S, Hayakawa T, Boyer J. Effect of UDCA on intracellular and biliary pH in isolated rat hepatocyte couplets and perfused livers. American Journal Of Physiology 1991, 260: g58-g69. PMID: 1987808, DOI: 10.1152/ajpgi.1991.260.1.g58.Peer-Reviewed Original ResearchConceptsBiliary HCO3- concentrationUrsodeoxycholic acidRat hepatocyte coupletsBiliary pHAcid loadEffect of UDCABile duct lumenHepatocyte coupletsIsolated rat hepatocyte coupletsBiliary epitheliumHCO3- concentrationDuct lumenRemoval of ClHCO3- exchangeRat liverLiverIPRLHepatocytesHypercholeresisPerfusateBileExcretionEpitheliumAmiloride