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The influence of vitamin B6 and folic acid on functional, biochemical and immunohistochemical characteristics of the cardiovascular system of rats with heart failure caused by monocrotaline

dc.contributor.advisorĐurić, Dragan
dc.contributor.otherSimić, Tatjana
dc.contributor.otherMilovanović, Branislav
dc.contributor.otherJakovljević, Vladimir
dc.creatorJakovljević Uzelac, Jovana
dc.date.accessioned2021-12-22T14:41:44Z
dc.date.available2021-12-22T14:41:44Z
dc.date.issued2021-09-16
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=8437
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:24736/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=53836041
dc.identifier.urihttps://nardus.mpn.gov.rs/handle/123456789/18856
dc.description.abstractU ovoj studiji istraživali smo efekte subhronične primene vitamina B6 i folne kiseline na ehokardiografske, kardiometaboličke, parametre oksidativnog stresa, histomorfometrijske i imunohistohemijske promene u srčanoj insuficijenciji izazvanoj monokrotalinom. Materijal i metode: Istraživanje je sprovedeno tokom 4 nedelje, i evaluirano je 9 eksperimentalnih grupa (8 životinja / grupi): kontrolne grupe (K fiziološki rastvor 1 ml/kg t.m. ip. jednokratno; K28 fiziološki rastvor 1 ml/kg t.m. ip. 28 dana), monokrotalinom-indukovana srčana insuficijencija (M 50 mg/kg t.m. ip. jednokratno), vitamin B6 (B6 7 mg/kg t.m. ip. 28 dana), folna kiselina (FK 5 mg/kg t.m. ip. 28 dana), vitamin B6 + folna kiselina (B6 7 mg/kg t.m. ip. 28 dana, FK 5 mg/kg t.m. ip. 28 dana), monokrotalin + vitamin B6 (M 50 mg/kg t.m. ip. jednokratno, B6 7 mg/kg t.m. ip. 28 dana), monokrotalin + folna kiselina (M 50 mg/kg t.m. ip. jednokratno, FK 5 mg/ kg t.m. ip. 28 dana) i monokrotalin + vitamin B6 + folna kiselina (M 50 mg/kg t.m. ip. jednokratno, B6 7 mg/kg t.m. ip. 28 dana, FK 5 mg/kg t.m. ip. 28 dana). Ehokardiografska merenja su sprovedena radi potvrde modela srčane insuficijencije indukovane monokrotalinom. Određivani su različiti kardiometabolički biomarkeri u krvi, aktivnosti enzima superoksid dismutaze (SOD) i glutation peroksidaze (GPx), sadržaj glutationa, parametri oksidativnog oštećenja proteina, tiol- i karbonilne grupe, sadržaj nitrotirozina i ukupna S-glutationilacija. Pored toga, određivani su histomorfometrijski i imunohistohemijski parametri (markeri proliferacije Ki67 i PCNA) srčanog tkiva pacova. Rezultati: Monokrotalin je doveo do hipertrofije zida desne komore i do povećanja dimenzije kardiomiocita zida leve komore, povećanja unutrašnjeg prečnika desne komore, praćene značajnim porastom troponina T, glukoze i von Willebrand-ovog faktora, uz očuvane parametre inflamacije i funkcije bubrega i jetre, kao i do promenjenih pokazatelja oksidativnog stresa. Tretman vitaminom B6 značajno je uticao na određene kardiometaboličke markere: troponin T, glukozu, HDL holesterol, aktivnosti aminotransferaza, alkalne fosfataze i amilaze, vrednosti von Willebrand-ovog faktora, uree i kreatinina. Pored toga, tretman vitaminom B6 je uticao na sadržaj glutationa i sadržaj reaktivnih karbonilnih derivata, kao i dimenzije kardiomiocita zida leve komore. Takođe, pokazano je smanjenje Ki67 i PCNA pozitivnosti u zidu desne komore. Efekti folne kiseline su se odrazili kroz značajno smanjenu aktivnost SOD-a, smanjenu Ki67 i PCNA pozitivnost u zidu desne komore i neznatno smanjen nivo ukupne glutationilacije. Primena folne kiseline modulisala je nivo oksidativnog stresa i uticala na smanjenje proliferacije kardiomiocita u zidu desne komore. Posle istovremene aplikacije vitamina B6 i folne kiseline, primećene su promene lipidnih parametara i aktivnosti određenih enzima, kao i smanjenje von Willebrand-ovog faktora, dok su određeni parametri oksidativnog stresa pokazali značajnije promene. Zajednička primena vitamina B6 i folne kiseline nije umanjila hipertrofiju zida desne komore izazvanu monokrotalinom, već je povećala vrednosti određenih histomorfometrijskih parametara. Ustanovljeno je i povećanje Ki67 i PCNA pozitivnosti u zidu desne komore nakon ko-aplikacije vitamina B6 i folne kiseline. Zaključci: Pojedinačni i kombinovani četvoronedeljni tretman vitaminom B6 i folnom kiselinom u eksperimentalnom modelu monokrotalinom indukovane srčane insuficijencije kod pacova doveo je do brojnih značajnih efekata na kardiometaboličke, parametre oksidativnog stresa, histomorfometrijske i imunohistohemijske parametre.sr
dc.description.abstractIn this study, it has been investigated the effects of vitamin B6 and folic acid on echocardiographic, cardiometabolic, oxidative stress-biomarker changes, histomorphometric and immunohistochemical changes in monocrotaline-induced heart failure (HF). Methods: The investigation was conducted during a 4-week period, using 9 experimental groups (8 animals/group): blank solution-exposed controls (K physiological saline 1ml/kg b.w. ip. one day; K28 physiological saline 1 ml/kg b.w. ip. 28 days), monocrotaline-induced HF (M 50 mg/kg b.w. ip. one day), vitamin B6 (B6 7 mg/kg b.w. ip. 28 days), folic acid (FA 5 mg/kg b.w. ip. 28 days), vitamin B6 + folic acid (B6 7 mg/kg b.w. ip. 28 days, FA 5 mg/kg b.w. ip. 28 days), monocrotaline + vitamin B6 (M 50 mg/kg b.w. ip. one day, B6 7 mg/kg b.w. ip. 28 days), monocrotaline + folic acid (M 50 mg/kg b.w. ip. one day, FA 5 mg/kg b.w. ip. 28 days), and monocrotaline + vitamin B6 + folic acid (M 50 mg/kg b.w. ip. one day, B6 7 mg/kg b.w. ip. 28 days, FA 5 mg/kg b.w. ip. 28 days). In order to confirm monocrotaline-induced HF, echocardiography was performed. Different cardiometabolic biomarkers in blood, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, glutathione content, parameters of oxidative damage of proteins, thiol- and carbonyl groups, nitrotyrosine content, and total S-glutathionylation were determined. As well as, histomorphometric and certain immunohistochemical parameters (proliferation markers Ki67 and PCNA) of rat cardiac tissue were designated. Results: The right ventricular wall hypertrophy, increase of dimension of cardiomyocyte of the left ventricle and increase of thickness of interventricle septum were followed by significant increase of troponin T, glucose and von Willebrand factor, and maintained parameters of inflammation and renal and liver function, as well as certain changes of oxidative stress parameters. The treatment with vitamin B6 significantly affected certain cardiometabolic markers: troponin T, glucose, HDL cholesterol, activities of aminotransferase, alkaline phosphatase and amylase, and values of von Willebrand factor, urea and creatinine. Furthermore, glutathione content and the content of reactive carbonyl derivates, as well as dimension of cardiomyocyte of the left ventricle free wall were affected by vitamin B6 treatment. Also, a decrease in Ki67 and PCNA positivity in the right ventricular wall was shown. The effects of folic acid were reflected through significantly decreasing SOD activity, reducing Ki67 and PCNA positivity in right ventricle wall, and slightly decreasing of total glutathionylation level. Folic acid administration modulated the level of oxidative stress, and affected the reduction of cardiomyocyte proliferation in wall of right ventricle. After treatment with co-administered vitamins B6 and folic acid there were detected some changes of lipid parameters and activities of certain enzymes, as well as the decrease of von Willebrand factor, while several parameters of oxidative stress were more pronounced. Co-application of vitamins B6 and folic acid did not attenuate hypertrophy of right ventricle wall, but aggravated the values of certain histomorphometric parameters. An increase in Ki67 and PCNA positivity in the right ventricular wall was also found after co-application of vitamin B6 and folic acid. Conclusions: Four week treatment with vitamins B6 and folic acid, alone and in combination, on experimental model of HF induced by monocrotaline in rats, showed many significant effects on cardiometabolic and oxidative stress parametersas well as on histomorphometric and immunohistochemical parameters.en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Медицински факултетsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175043/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175052/RS//
dc.rightsopenAccessen
dc.rights.urihttps://creativecommons.org/licenses/by-nd/4.0/
dc.sourceУниверзитет у Београдуsr
dc.subjectsrčana insuficijencijasr
dc.subjectheart failureen
dc.subjectmonocrotalineen
dc.subjectvitamin B6en
dc.subjectfolic aciden
dc.subjectbiochemical markersen
dc.subjectoxidative stressen
dc.subjectimmunohistochemical markersen
dc.subjectraten
dc.subjectmonokrotalinsr
dc.subjectvitamin B6sr
dc.subjectfolna kiselinasr
dc.subjectbiohemijski markerisr
dc.subjectoksidativni stressr
dc.subjectimunohistohemijski markerisr
dc.subjectpacovsr
dc.titleUticaj vitamina B6 i folne kiseline na funkcionalne, biohemijske i imunohistohemijske karakteristike kardiovaskularnog sistema pacova sa srčanom insuficijencijom izazvanom monokrotalinomsr
dc.title.alternativeThe influence of vitamin B6 and folic acid on functional, biochemical and immunohistochemical characteristics of the cardiovascular system of rats with heart failure caused by monocrotalineen
dc.typedoctoralThesis
dc.rights.licenseBY-ND
dcterms.abstractЂурић, Драган; Јаковљевић, Владимир; Симић, Татјана; Миловановић, Бранислав; Јаковљевић Узелац, Јована; Утицај витамина Б6 и фолне киселине на функционалне, биохемијске и имунохистохемијске карактеристике кардиоваскуларног система пацова са срчаном инсуфицијенцијом изазваном монокроталином; Утицај витамина Б6 и фолне киселине на функционалне, биохемијске и имунохистохемијске карактеристике кардиоваскуларног система пацова са срчаном инсуфицијенцијом изазваном монокроталином;
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/78556/Disertacija_11980.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/78557/Izvestaj_Komisije_11980.pdf
dc.identifier.rcubhttps://hdl.handle.net/21.15107/rcub_nardus_18856


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