Abstract

EffectofaBenignProstaticHyperplasia(BPH)Xenobiotic-Crotonmembranaceus Müll.Arg. Root Extract on CYP1A2,CYP3A4, CYP2D6, and GSTM1 Drug Metabolizing Enzymes in Rat Model.

Introduction:CrotonmembranaceusMüll.Arg., rootextracthasbeen scientificallyandclinicallyproventobeefficaciousinthemanagementofBPH.However,its effect onliverdrug-metabolizingenzymeshasnotbeenestablished.This study aimed to determine the effect of the plant extract on phase I and phase II drug-metabolizingenzyme.

Materialsandmethods:Fifteen(15)castrated-testosteroneBPHinducedmaleAlbinoWister ratsweighingbetween120-150gramswererandomlydividedinto3groupsof5ratseach (GroupsII-IV).Five(5)uncastratedratsGroupIwasusedasanegativecontrol,receiving onlydistilledwater.GroupIIwasadministered30mg/kgb.wtextractsofC.membranaceus. GroupIIIwasthemodelgroupwhileGroupIVwasadministered0.5mg/kgb.wtfinasteride anditwasusedasthepositivecontrol.BPHwasinducedingroupsII-IVbyadministering testosteronepropionate,3mg/kgb.wtfor28daysaftera7-daypostcastrationrestperiod. Ratswereeuthanizedandindividualliversharvestedformicrosomepreparation.Theliver microsomeswereassayedfor,PhaseIDrugMetabolizingEnzymes(DME);CYP1A2, CYP3A4,CYP2D6,andphaseII;GST-M1using Enzyme-Linked Immuno-Sorbent Assay (ELISA) techniques.

Results:SignificantdifferencesinphaseIenzymes;CYP1A2,CYP3A4,CYP2D6,(p=0.02, 0.00,0.01)respectively.PhaseIIenzymes,GSTM1,showedastatistical significance(p=0.01).C.membranaceusinducedCYP1A2strongly,GSTM1modestly,andhadaninhibitoryeffectonCYP2D6.

Conclusion:CrotonmembranaceusinducesandinhibitssomephaseImetabolizingenzymes whilemoderatelyinducingphaseIImetabolizingenzymes. Careshouldbetakenintheuseof phytotherapy in conjunction with other drugs.


Author(s): Ongong'ARoyronaldOchieng',GeorgeA.Asare,YvonneAnanga,RichardH.Asmah,HabiburRahman

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