Show simple item record

The effect of chronic administration of cisplatin and diethyl ester ligand (S,S)- ethylenediamine-N,N’-di-2-(3-cyclohexyl) dipropionate dihydrochloride (L3) and its complexes with Pt (IV) and Pd (II) on rat cardiac muscle and coronary circulation

dc.contributor.advisorŽivković, Vladimir
dc.contributor.otherRosić, Gvozden
dc.contributor.otherJakovljević, Vladimir
dc.contributor.otherSabo, Tibor
dc.creatorŠmigić, Jelena
dc.date.accessioned2020-02-26T15:44:44Z
dc.date.available2020-02-26T15:44:44Z
dc.date.available2020-07-03T15:16:06Z
dc.date.issued2019-10-25
dc.identifier.urihttp://eteze.kg.ac.rs/application/showtheses?thesesId=7113
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/12001
dc.identifier.urihttps://fedorakg.kg.ac.rs/fedora/get/o:1203/bdef:Content/download
dc.description.abstractUvod: Nedostaci cisplatine i drugih registrovanih citostatika (neželjena dejstva, pojava rezistetnosti i visoka toksičnost) otvorila je mogućnost istraživanja u pravcu sinteze novih jedinjenja sa istom ili većom efikasnošću i smanjenom toksičnošću. Kardiotoksičnost je jedna od najčešćih i najozbiljnijh komplikacija primene hemoterapeutika u terapiji karcinoma. Efekti cisplatine i novih metalnih antineoplastičnih agenasa na srce i koronarnu cirkulaciju su gotovo nepoznati. Cilj: Cilj ovog istraživanja je bio ispitivanje i upoređivanje efekata cisplatine (referentna supstanca) i dietil-estra liganda (S,S)etilendiamin-N,N-di-2-(3- cikloheksil)dipropanoat-dihidrohlorida i njegovih kompleksa sa Pt(IV) i Pd(II) na modelu izolovanog srca pacova perfundovanog po Langendorff-ovom modelu. Materijal i metode: Istraživanje je dizajnirano kao eksperimentalna studija sprovedena in vivo i ex vivo. Životinje u eksperimentalnim grupama su tokom četiri nedelje dobijale intraperitonealno po jednu dozu (4 mg/kg telesne mase) ispitivanog jedinjenja, dok su životinje u kontrolnim grupama jednom nedeljno dobijale jednaku zapreminu fiziološkog rastvora ili dimetil sulfoksida (DMSO). Određivani su sledeći parametri srčanog rada: srčana frekvencija - HR, maksimalna stopa promene pritiska u levoj komori - LV(dP/dt)max, minimalna stopa promene pritiska u levoj komori - LV(dP/dt)min, sistolni - SLVP i dijastolni pritisak u levoj komori - DLVP i koronarni protok – CF. Iz uzoraka plazme i koronarnog venskog efluenta spektrofotometrijski su određivani NO2-, TBARS, O2ˉ i H2O2, dok su iz lizata eritrocita na isti način mereni enzimi antioksidacione zaštite (SOD, CAT i GPH). Rezultati: Rezultati ovog istraživanja pokazuju da u primenjenoj dozi i dužini ekspozicije nijedno od ispitivanih jedinjenja nije oštetilo funkciju izolovanog srca pacova tj. nisu ostvarili kardiodepresivni efekat, a sa druge strane novi ligand (L3) ali i njegovi kompleksi sa četvorovalentnom platinom (K3) i dvovalentnim paladijumom (PdL3) imaju respektabilan i obećavajući potencijal ka mobilizaciji antioksidacionih enzima. Zaključak: Dobijeni rezultati istraživanja daju originalan i veoma važan doprinos razumevanju razvoja kardiotoksičnosti izazvane hemoterapeuticima, kao i ispitivanju kardiotoksičnog potencijala potencijalno novih antikancerskih lekova.sr
dc.description.abstractIntroduction: Deficiencies of cisplatin and other registered cytostatics (side effects, resistance and high toxicity) have opened up the possibility of research towards the synthesis of new compounds with the same or greater efficacy and reduced toxicity. Cardiotoxicity is one of the most common and serious complications of the use of chemotherapeutics in cancer therapy. The effects of cisplatin and new metal antineoplastic agents on the heart and coronary circulation are almost unknown. Aim: The aim of this study was to investigate and compare the effects of cisplatin (reference substance) and diethyl-ester ligand (S,S)ethylenediamine-N,N-di-2-(3-cyclohexyl)dipropanoate dihydrochloride and its complexes with Pt(IV) and Pd(II) on an isolated rat heart model perfused according to the Langendorff technique. Material and methods: The investigation was designed as an experimental study conducted in vivo and ex vivo. Animals in the experimental groups received intraperitoneally one dose (4 mg/kg body weight) of the test compound over four weeks, whereas animals in the control groups received an equal volume of saline or dimethyl sulfoxide (DMSO) once a week. The following parameters of heart function rate were determined: heart rate - HR, maximal rate of pressure development in left ventricle - LV(dP/dt)max, minimum rate of pressure development in left ventricle - LV(dP/dt)min, systolic - SLVP and diastolic pressure in left ventricle - DLVP and coronary flow - CF. NO2-, TBARS, O2ˉ and H2O2 were determined spectrophotometrically from plasma and coronary venous effluent samples, while antioxidant protection enzymes (SOD, CAT аnd GPH) were measured on the same way from erythrocyte lysates. Results: The results of this study show that at the administered dose and exposure length, none of the compounds tested impaired the function of the isolated rat heart, ie. have not achieved cardio-depressant effects, while on the other hand, the new ligand (L3) and also its complexes with four-valent platinum (K3) and divalent palladium (PdL3) have a respectable and promising potential for mobilizing antioxidant enzymes. Conclusions: The findings of present research provide an original and very important contribution to understanding the development of cardiotoxicity induced by chemotherapeutics, as well as examining the cardiotoxic properties of potentially new anticancer drugs.en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Крагујевцу, Факултет медицинских наукаsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175043/RS//
dc.rightsopenAccessen
dc.sourceУниверзитет у Крагујевцуsr
dc.subjectcisplatinasr
dc.subjectcisplatinen
dc.subjectcyclohexyl compoundsen
dc.subjectcardiotoxicityen
dc.subjectcoronary flowen
dc.subjectoxidative stressen
dc.subjectisolated rat hearten
dc.subjectcikloheksil-jedinjenjasr
dc.subjectkardiotoksičnostsr
dc.subjectkoronarni protoksr
dc.subjectoksidacioni stressr
dc.subjectizolovano srce pacovasr
dc.titleUticaj hronične primene cisplatine i dietil-estra liganda (Ѕ,Ѕ)-etilendiamin-N,N'-di-2-(3-cikloheksil) dipropionat dihidrohlorida (L3) i njegovih kompleksa sa Pt(IV) i Pd(II) na srčani mišić i koronarnu cirkulaciju pacovasr
dc.title.alternativeThe effect of chronic administration of cisplatin and diethyl ester ligand (S,S)- ethylenediamine-N,N’-di-2-(3-cyclohexyl) dipropionate dihydrochloride (L3) and its complexes with Pt (IV) and Pd (II) on rat cardiac muscle and coronary circulationen
dc.typedoctoralThesisen
dc.rights.licenseBY-NC-ND
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/48838/Disertacija.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/48839/Jelena_Smigic_Medicinski.pdf


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record