Quercetin Prevents Methotrexate-induced Hepatotoxicity without Interfering Methotrexate Metabolizing Enzymes in Liver of Mice

Journal of Applied Biological Sciences

Birsen AYDIN¹ 

关键词: Methotrexate;    quercetin;    drug metabolizing enzymes;    herb-drug interactions;    oxidative stress;   

DOI  :  

学科分类：生物科学（综合）

来源: Nobel Bilim ve Arasirma Merkezi/Nobel Science and Research Cente

【 摘 要 】

Drug-herbinteractionsareofgreatconcernthatmayleadtoincreasedsideeffectsanddecreasedefficacyofthedrugs.Thisstudyexaminedtheeffectofquercetin(QE)onthemicrosomaldrugmetabolizingandantioxidantsystemsinmethotrexate(MX)treatedmice,andalsodeterminedwhetherthesesubstanceaffectthetoxicityordetoxificationofMX.AdministrationofMXat10mg/kg/day,i.m.forconsecutive3days(on7,8and9.daysofexperiment)impairedantioxidantmechanismsandcausedsubstantialincreasesinthelevelsliverinjurymarkersinserum.PretreatmentwithQE(50mg/kg/day,p.o.for10days)inhibitedMX-inducedliverinjuryandoxidativestressbydecreasingmicrosomallipidperoxidation,increasingcellularglutathionecontentandmaintainingthelevelsofantioxidantenzymesclosetocontrolvalues.MXmarkedly(P<0.05)decreasedtheactivityofthehepaticphaseIenzymescytochromeP450reductase,cytochromeb5reductase,anilinehydroxylaseandaldehydeoxidase.Ingeneral,administrationofQEincombinationwithMXdidnotsignificantly(P>0.05)affecttheseenzymeactivities.ThisisespeciallynoteworthyintermsofaldehydeoxidasewhichisthekeycytosolicenzymeinMXmetabolism.AdministrationofQEalongwithMXsignificantly(p<0.05)increasedtheactivityofthephaseIIenzymesglutathioneS-transferaseandDT-diaphoraserelativetotheMXtreatedgroup.Basedontheseresults,thecombinationofQEorVAwithMXtherapymayrepresentanovelandhighlyeffectivestrategyforreducingMXhepatotoxicity,withoutalteringtheoutcomeofMXmetabolisim.

【 授权许可】

Unknown