β-Naphthoflavone protects mice from aristolochic acid-l-induced acute kidney injury in a CYPIA dependent mechanism.pdf

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β-Naphthoflavone protects mice from aristolochic acid-l-induced acute kidney injury in a CYPIA dependent mechanism.pdf

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ActaPharmacologicaSinica (2009)30：1559—1565 ~2009CPSandSIMM Allrightsreserved1671-4083／09 $32．00 @ www．nature．com／aps OriginalArticle 13-Naphth0fIaV0neprotectsmicefromaristolochic acid--I--inducedacutekidneyinjuryinaCYPIA dependentmechanism YingXIAO，，XiangXUE，，，Yuan-fengWU_，Guo—zhengXINr，YongQIAN。，Tian—peiXIE。，Li—kunGONG ·，JinREN， CentreforDrugSafetyandEvaluationResearch StateKeyLaboratoryofNewDrugResearchShanghaiInstituteofMateriaMedica ChineseAcademyofSciences，Shanghai201203,China；GraduateSchooloftheChineseAcademyofSciences,Shanghai201203, China；。ShanghaiTenGenBiomedicalCoLtd,China Aim：TheroleofCYP1AintheprotectionofaristoIochicacid(AA)t—inducednephrotoxicityhasbeensuggested．Inthepresentstudywe investigatedtheeffectsofp—naphthoflavone(BNF)，anon—carcinogenCYPIAinducer，onAAI—inducedkidneyinjury． Methods：Micewerepretreatedwith8Om kgBNFbydailyintraperitonealinjection(ip)for3daysfollowedbyasingleipof1Om kg AAI．AAIanditsmajormetabolitesinblood，liverandkidney．theexpressionofCYP1A1andCYP1A2inmicrosomesofIiverandkidney aswellasthenephrotoxicitywereevaluated． Results：BNFpretreatmentpreventedAAI—inducedrenaIdamagebyfacilitatingthedisposaIofAAlinIiver．BNFpretreatmentinduced theexpressionofCYP1A1inbothliverandkidney；buttheinductionofCYP1A2wasonlyobservedinIiver． Conclusion：BNFpreventsAAI—inducedkidneytoxicityprimarilythroughCYPIAinduction． Keywords：aristolochicacid；kidneyinjury；beta—naphth0fIavone：biotransformation；CYPIA ActaPharmacologicaSinica(2009)30：1559-1565；doi：10．1038／aps．2009．156 IntrOduCtiOn tion／detoxificationofavarietyofprocarcinogenssuchas Aristolochicacid fAA)isam ixtureofstructurallyrelated 3-methylcholanthrener3-MC)[I．Ithasbeenreportedthatin nitrophenanthrenecarboxylicacidsanditsma