Abstract
ABSTRACT - BACKGROUND:Immunosuppressive drugs are essential for reducing the rejection risk in post-transplant patients, which is commonly associated with this procedure. However, side effects of those drugs on the hypothalamic nuclei involved in the food intake regulation, excessive weight gain, and also associated comorbidities are still unknown.PURPOSE: The purpose of this study was to analyze possible changes in the neuronal morphology and cell density in the paraventricular nuclei, lateral hypothalamic area, dorsomedial nuclei, and ventromedial and arcuate nuclei in Wistar rats submitted to immunosuppressive treatment with tacrolimus (TAC) or mycophenolate mofetil (MMF).METHODS: Adult male Wistar rats were randomly assigned to the following groups according to the oral treatment administered for 14 weeks: control, sham (placebo), TAC (1 mg/kg of weight), and MMF (30 mg/kg of weight). After treatment, the animals were sacrificed and their brains fixed for later histological staining. Subsequently, the slides were photodocumented for stereological analysis of the hypothalamic nuclei.RESULTS: All experimental groups showed a weight gain throughout the study. There was no significant difference in neuronal density/number of cells in the hypothalamic nuclei between groups. Morphological changes were not detected in the hypothalamic neurons.CONCLUSION: Treatments with immunosuppressants could not modify the morphological and cell density aspects of the hypothalamic nuclei during this supplementation period.
Highlights
Chionimfpluoetcnaicltâaiamr eaiscsvoeasraieartçniãgvoo:lddvoiedBcoaisalisnbeareSiinldvgaaes-NsvteaãtroizeaWsliBme, eQansutitaraerxsa?eseCds,teDuedreoMsseoaxnupgraerarEimGmHeen,ntCotoaenl.lahAoeBsFCqFDu, HisAterorqmssBoarnmaPso.CsAeirqnDuoiegsd.ea2gd0ua2im1p;er3en4sts(o4ão)e:mep1o6lrot3an6lg.aohptóptspradsz:eo/s/?vdaAosBic.CuolDragriA/z1arq0çã.1Bo5rae9ss0oC/f0airg1Do0gi2gá-.s62t7r0i2c2a012;e304e2(s21p)0l:ee0n105e28ct1eo.1mD6i3Oa6I: in/f1lu0e.1n5c9ia0/a01v0a2ri-a6ç7ã2o0d2o02c1a0li0b0r1eed1a5s81varizes e as taxas de ressangramento na esquistossomose no seguimento em longo prazo? ABCD Arq Bras Cir Dig. 2021;34(2):e1581
A bula aprovada pela Agência Nacional de Vigilância Sanitária (ANVISA) em 29 de outubro de 2015 do medicamento Cellcept®, utilizado no estudo como tratamento com micofenolato mofetil (MMF) informa que nos exames realizados, entre 3% e 10% dos pacientes tiveram vertigens, depressão, convulsões, tremores, neuropatias, alucinações, delirium, entre outros efeitos neurológicos e, além destes, apresentaram ganho de peso classificado como muito comum nos casos de transplante cardíaco e comum quando esses pacientes foram submetidos a transplante renal e hepático
Summary
BACKGROUND: Immunosuppressive drugs are essential for reducing the rejection risk in AABBSSptThoTRosRAste-ACtdrCTarTnu-sgp-sBlaoBannacttkcphkgaegtrihoreyounputnosnd,twhd: a:hTliaThcmhheeiicstrntceruoeacmatlmetmmi eionennvntloytlovaoefssdfocihccnhioatohitceieecdefowfofitodrhriptnhpatiaatskitepeienrrontesctgesuwdlwuaittrihietoh.nHs,csoehcwxhicseietsvostesosriosv, oesmimdwieaeiasiegisfshifsetwcgwtisatihitonhf, paprnerdevivoaiolusuosseaepspsisoioscoidadeteeodofcfvoavmarirociecrbesisdisiitsbieblseleeaedredinisngtgilel esuosnopkphnhoaawggono.ggPaasUtsRrtircPicOddeSevEav: asTcshuceulaplaruirzriazpatoitosieonnoafanntdhdisspssplteluendneyectcwotaomsmytoy (Ea(EGnGaDlDySzS)e)inpinoasassssiobsolceicaciathitoaionnngwewsitihitnhptphoeostsnoteopupereorarnataitvlievmeeoenrpndhdoooslcosocgopypiacinctdhthecerarllapdpyey. nH. sHiotoywwienevtevhere,rs,ptsautrudadiveeiesnshtrhaicavuevlaesrhsnhouowcwlneni, vlsavbauartebierchimrecaaesilvtstihoeryedrrpecotoucotufrhriremaerslenamoncmpuecinehcoeaasesgrupseeppeaape,clricdaevioaslalsrylrsliiyvcoeaemafstterfeetaderaniratdmllolnoenbunnglcetg-lewet-editi,terihmanrnmgtadfcrorvfeoolecllolnuilmotwrrwrou-esmu-nup(ecTp.deA.iCAaaA)lifmotaiemrn:rdm:TpyaoTocroocsautp-asahostseeepsnesenossrulsaactttlheitevheimeeinoiemifnmWepdtipiasloatc(saMtccrtoMorpaonFtin)cs. btrtMteehrheaeEaatTomtvHrmiaoeOlenrtDnrtoetSoaf:oftemAfpsdepoaunatplitttehiaenmadntgmastelseisanuslWisubvtbimeasmrtreaiitcdritteetrfseadotdrast1notw4odeEwrEGbeeGlDeerDkaSesnS.d:d.McinoMogemnettlhrrtyoehoalco,dsusdsshri:srgae:TnmnThehcid(repitrtyltaoay-csf-ettishxebiexrop)fppa,ooaTtlilAtseoiCtenw-nto(isn1tpsgsmeusgrgubar/botmkiumvgipetoitstefetaedwncddectoiootgorshdEctiEGo)n,GpgDaDinSctdoS wMweMererFefo(f3oll0ollowmweged/dkfgoforormf mwoeoriergehthtt)ha. anAnfftifveievr etyryeeeaatarmsr.seT.nThthe, eythyweweaerneriemddaivlisivdiwdeeedrdeininstaotcotrwitfwioceogdgroaronuduppst,hsa,eacirccbocorradridinnisngfgitxoteodthtfheoer plpoaotretrartalhplisprteoreslossugsuirceraeldsdrtoraopinp,imn, mgo.orSeruebosorerlqeleusssesnthttlhay,antnh3e300%sl%i,da,eansndwdceocreompmphpaoarteoredddowcwiutimhthethntheteebdbefehohraavstivoeiroreroooflofegesioscoaplphahanagagelyeasalisl vsoavlatfarutitrecdhiecyepes. hsoTayhsanpetndo-rdoetthphtwaheelaaersramartnatiicveoteenosuiofvgcfabnlerbliifiec.ileceReaedsEndiSntciUngadglLiifrbTfereSeecr:ruceAunrwrlcrlereheenexincnpnecene.crRe.iomRuemresounspnutlaaatlrlslte:gsddA:reoAnstushispigtiesgyn/snipnfhiirufoceimacw-anoebntdpetrreaerroedwafduteciucivegtcelihltositdonignanaotitoannhnettwhhtharheoysepueoeogaabtrhhlroysaleyulaartanvmtnedhiddec ldanCdetuOeescpsNlppeitCioietLbesaUtea-ntSonwiIpnOeinecNrcrnear:eatgTiasrvreeoseaeuitnvpminasd.erdiinMacitaemsomsrwepcetihteathoerlilrbidomdeugmruricirnuwainnlghogcefshofnuaolplnolclpgoworewem-ssu-spwupaapentrthetshadcnatoottwuhtwlaeddasenspctoocreetocn-mtnteortodoprdoleliienlrflyaedttdthibhvebyeeyhemdyenoapndrtodpoatohshwcosaocllaoopsmgpiiciociccatbhltnshaeeeneruradrvrapoecpyndey.sll. A esse respeito, o objetivo do estudo foi analisar possíveis alterações na morfologia neuronal e densidade celular nos núcleos paraventriculares (PA), área hipotalâmica lateral (LH), núcleos dorsomedial (DM), ventromedial (VM) e núcleos arqueados (ARC) em ratos Wistar submetidos a tratamento imunossupressor com TAC ou MMF.
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