2011-Captopril and telmisartan treatments attenuate cadmium-induced testicular toxicity in rats

doi:10.1111/j.1472-8206.2011.00974.x

ORIGINALARTICLE

Captoprilandtelmisartantreatmentsattenuatecadmium-inducedtesticulartoxicityinrats

AmrA.Fouada*,IyadJresatb

DepartmentofBiomedicalSciences,PharmacologyDivision,CollegeofMedicine,KingFaisalUniversity,Al-Ahsa,SaudiArabiab

DepartmentofBiomedicalSciences,PathologyDivision,CollegeofMedicine,KingFaisalUniversity,Al-Ahsa,SaudiArabia

a

Keywords

cadmiumtoxicity,captopril,rats,

telmisartan,testis

ABSTRACT

Received24February2011;revised6May2011;accepted4July2011

*Correspondenceandreprints:amrfouad65@yahoo.com

Thepossibleprotectiveeffectofcaptopril,anangiotensin-convertingenzymeinhibitor,vs.telmisartan,anangiotensinII-receptorantagonist,wasinvestigatedinratswithtesticularinjuryinducedbyasinglei.p.injectionofcadmiumchloride(2mg/kg).Captopril(60mg/kg/day,p.o.)andtelmisartan(10mg/kg/day,p.o.)weregivenfor veconsecutivedays,starting3daysbeforecadmiumadministration.Bothagentssigni cantlyincreasedserumtestosteronelevel,whichwasreducedbycadmium,suppressedlipidperoxidation,restoredthedepletedreducedglutathione,decreasedtheelevationsofnitricoxide,tumornecrosisfactor-a,andcadmiumionlevels,andattenuatedthereductionsofseleniumandzincionsintesticulartissueresultedfromcadmiumadministration.Immunohistochemicalanalysisrevealedthatbothcaptoprilandtelmisartansigni cantlyreducedthecadmium-inducedexpressionofinduciblenitricoxidesynthase,nuclearfactor-jB,Fasligand,andcaspase-3intesticulartissue.Thedifferencesbetweentheresultsobtainedwithcaptoprilandtelmisartanwereinsigni cant,suggestingthatbothdrugsequallyprotectedthetesticulartissuefromthedetrimentaleffectsofcadmium.

INTRODUCTION

Cadmiumisoneofthemostenvironmentallyabundanttoxicmetalswhichadverselyaffectsnumerousbodyorgans.Occupationalexposuretocadmiumoccursbecauseofworkingwithcadmium-containingpigments,plastics,glass,metalalloys,andelectrodematerialinbatteries.Non-occupationalexposurepredominantlyresultsfromsmoking,airpollution,andconsumptionofcadmium-contaminatedwaterandseafoods[1].Acuteandchroniccadmiumtoxicityisassociatedwithseveretesticulardamage,inbothhumansandanimals[2].Previousstudiesdemonstratedasigni cantdecreaseintesticularweightswithreducedandrogensecretionasaresultofexposuretocadmiumindicatingthattestic-ularendocrinefunctionhadbeencompromised[3,4].Oxidativestressandin ammationarethemainfactors

implicatedincadmium-inducedtissueinjury.Also,severalantioxidantsandanti-in ammatoryagentswerefoundtobeeffectiveinminimizingcadmium-inducedtesticulartoxicitywithrestorationoftesticularsteroido-genesis[5–7].

AngiotensinII,thecentralproductofrenin-angioten-sinsystem,inducestissueoxidativestress,in ammation,andapoptosisbyactivatingtheangiotensinIItype1(AT1)receptor[8].Captopril,anangiotensin-convertingenzymeinhibitor,decreasesthecirculatingandtissuelevelsofangiotensinII.Also,asathiol-containingcompound,captoprilpossessespowerfulantioxidantactivity,scavengesdifferenttypesofreactiveoxygenspecies,andpreventslipidperoxidation[9–11].Ontheotherhand,telmisartanisahighlyselectiveAT1-receptorantagonistandalsoactsasapartialagonistonthenuclearperoxisomeproliferator-activatedreceptor-c

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Fundamental&ClinicalPharmacology27(2013)152–160

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