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Abstract
Acutetreatmentwithmetforminhasaprotectiveeffectinmyocardialinfarctionbysuppressionof inflammatoryresponsesduetoactivationofAMP-activatedproteinkinase(AMPK).Inthepresentstudy, the effectofchronicpre-treatmentwithmetforminoncardiacdysfunctionandtoll-likereceptor4 (TLR4) activitiesfollowingmyocardialinfarctionandtheirrelationwithAMPKwereassessed.Male Wistar ratswererandomlyassignedtooneof5groups(n¼6): normalcontrolandgroupswereinjected isoproterenolafterchronicpre-treatmentwith0,25,50,or100mg/kgofmetformintwicedailyfor14 days.Isoproterenol(100mg/kg)wasinjectedsubcutaneouslyonthe13thand14thdaystoinduceacute myocardialinfarction.Isoproterenolalonedecreasedleftventricularsystolicpressureandmyocardial contractility indexedasLV dp/dtmax and LV dp/dtmin. Theleftventriculardysfunctionwassignificantly lowerinthegroupstreatedwith25and50mg/kgofmetformin.Metfrominmarkedlylowered isoproterenol-inducedelevationinthelevelsofTLR4mRNA,myeloiddifferentiationprotein88 (MyD88), tumornecrosisfactor-alpha(TNF-α), andinterleukin6(IL-6)inthehearttissues.Similar changes werealsoseenintheserumlevelsofTNF-α and IL-6.However,thelowerdosesof25and50mg/ kg weremoreeffectivethan100mg/kg.PhosphorylatedAMPKα (p-AMPK) inthemyocardiumwas significantly elevatedby25mg/kgofmetformin,slightlyby50mg/kg,butnotby100mg/kg.Chronic pre-treatmentwithmetforminreducespost-myocardialinfarctioncardiacdysfunctionandsuppresses inflammatoryresponses,possiblythroughinhibitionofTLR4activities.Thismechanismcanbe considered asatargettoprotectinfarctedmyocardium
| Item Type: | Article |
|---|---|
| Additional Information: | cited By 10 |
| Uncontrolled Keywords: | Metformin Myocardialinfarction Inflammation AMP-activatedproteinkinase Toll-likereceptor |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Unnamed user with email gholipour.s@umsu.ac.ir |
| Date Deposited: | 24 Jul 2017 08:02 |
| Last Modified: | 18 Feb 2019 09:57 |
| URI: | http://eprints.umsu.ac.ir/id/eprint/570 |
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