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Role of thiamine in inhibition of oxidative stress of mitochondries and endoplasmic reticulum in animal model of doxorubicin-induced cardiotoxicity

dc.contributor.advisorNikolić Turnić, Tamara
dc.contributor.otherJeremić, Nevena
dc.contributor.otherSazdanović, Maja
dc.contributor.otherTodorović, Zoran
dc.creatorRadonjić, Tanja
dc.date.accessioned2021-10-29T11:19:04Z
dc.date.available2021-10-29T11:19:04Z
dc.date.issued2021-04-21
dc.identifier.urihttp://eteze.kg.ac.rs/application/showtheses?thesesId=8147
dc.identifier.urihttps://fedorakg.kg.ac.rs/fedora/get/o:1378/bdef:Content/download
dc.identifier.urihttps://nardus.mpn.gov.rs/handle/123456789/18705
dc.description.abstractCilj ovog istraživanja je bio ispitati potencijalnu ulogu tiamina u inhibiciji oksidacionog stresa uzrokovan nakon akutne primene visoke kumulativne doze antraciklinskog citostatika doksorubicina i ispitati potencijalne nove molekularne mehanizme kojima tiamin i doksorubicin, samostalno ili u kombinaciji ostvaruju svoje efekte na kardiovaskularni sistem. Istraživanje je obuhvatilo 48 pacova muškog pola Wistar albino soja (12 pacova po grupi), starosti 12 nedelja i prosečne telesne mase 350 grama. U odnosu na tretman, sve životinje su bile podeljene u četiri grupe: Kontrolna grupa, grupa pacova bez tretmana; Doksorubicin grupa, (doksorubicin jednokratno, u dozi od 15 mg/kg telesne težine i.p).; Tiamin grupa, (tiamin hidrohlorid u dozi od 25 mg/kg telesne težine dnevno tokom 7 dana); Tiamin+Doksorubicin grupa, (tiamin hidrohlorid u dozi od 25 mg/kg telesne težine dnevno tokom 7 dana, a nakon toga 8.og dana doksorubicin u dozi 15 mg/kg telesne težine). U zavisnosti od grupe, eksperiment je podrazumevao primenu tiamina i/ili nakon 72 časa aplikaciju doksorubicinu. Nakon toga životinje su žrtvovane da bi se sprovela istraživanja na srcu, izolovala krv i tkivo leve komore srca. Primena doksorubicina je značajno uticala na povećanje aktivnosti srčanih enzima, CK-MB, Troponina 1 i LDH, dok je primena tiamina značajno smanjila koncentracije u odnosu na kontrolne grupe. Sedmodnevna primena tiamina u terapijskim dozama je efikasna u pogledu povećanja ejekcione frakcije leve komore, dovela do povećanja kontraktilne sposobnosti srca i to povećanjem nivoa dp/dt max i dp/dtmin, doveo do značajne redukcije nastalog oksidacionog stresa i do povećanja odbrambenih mehanizama antioksidativnog sistema, čime je potvrđen kardioprotektivni efekat tiamina i kardiotoksični efekat doksorubicina. Morfometrijskim metodama i patohistološkim analizama tkiva srca potvrdili smo citotoksične efekte doksorubicina i zaštitne efekte tiamina. Rezultati su ukazali na značajan kardioprotektivni efekat tiamina na modelu doksorubicinom-indukovane kardiotoksičnosti.sr
dc.description.abstractThe aim of this study was to examine the potential role of thiamine in inhibiting oxidative stress caused after acute administration of a high cumulative dose of the anthracycline cytostatic doxorubicin and to examine potential new molecular mechanisms by which thiamine and doxorubicin, alone or in combination, exert their effects on the cardiovascular system. The study included 48 male Wistar albino rats (12 rats per group), aged 12 weeks and an average body weight of 350 grams. In terms of treatment, all animals were divided into four groups: Control group, group of rats without treatment; Doxorubicin group, (doxorubicin once, at a dose of 15 mg / kg body weight i.p); Thiamine group, (thiamine hydrochloride at a dose of 25 mg / kg body weight daily for 7 days); Thiamine + Doxorubicin group, (thiamine hydrochloride at a dose of 25 mg / kg body weight daily for 7 days, and then on the 8th day doxorubicin at a dose of 15 mg / kg body weight). Depending on the group, the experiment involved the use of thiamine and/or after 72 hours the application of doxorubicin. After that, the animals were sacrificed in order to conduct research on the heart, isolate blood and tissue of the left ventricle of the heart. The use of doxorubicin significantly increased the activity of cardiac enzymes, CKMB, Troponin 1 and LDH, while the use of thiamine significantly reduced concentrations compared to control groups. Seven-day use of thiamine in therapeutic doses is effective in increasing the ejection fraction of the left ventricle, led to an increase in cardiac contractility by increasing the levels of dp/dt max and dp/dtmin, led to a significant reduction in oxidative stress and increased defense mechanisms of the antioxidant system. Thus confirming the cardioprotective effect of thiamine and the cardiotoxic effect of doxorubicin. We confirmed the cytotoxic effects of doxorubicin and the protective effects of thiamine by morphometric methods and pathohistological analyzes of heart tissue. These results indicated a significant cardioprotective effect of thiamine on the doxorubicin-induced cardiotoxicity model. Key words: thiamine, doxorubicin-induced cardiotoxicity, rat heart, oxidative stressen
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Крагујевцу, Факултет медицинских наукаsr
dc.rightsopenAccessen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceУниверзитет у Крагујевцуsr
dc.subjecttiamin, doksorubicinom-indukovana kardiotoksičnost, srce pacova, oksidacioni stressr
dc.subjectthiamine, doxorubicin-induced cardiotoxicity, rat heart, oxidative stressen
dc.titleUloga tiamina u inhibiciji oksidativnog stresa mitohondrija i endoplazmatskog retikuluma u animalnom modelu doksorubicinom indukovane kardiotoksičnostisr
dc.title.alternativeRole of thiamine in inhibition of oxidative stress of mitochondries and endoplasmic reticulum in animal model of doxorubicin-induced cardiotoxicityen
dc.typedoctoralThesis
dc.rights.licenseBY
dc.identifier.fulltexthttps://nardus.mpn.gov.rs/bitstream/id/77384/Tanja_Radonjic_Medicinski.pdf
dc.identifier.fulltexthttps://nardus.mpn.gov.rs/bitstream/id/77383/Doctoral_thesis_11667.pdf
dc.identifier.rcubhttps://hdl.handle.net/21.15107/rcub_nardus_18705


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