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Effects of hyperhomocysteinemia on parameters of oxidative stress and activity acetylcholinesterase enzyme in plasma and heart rats: the role of gasotransmitters (NO,H2S and СО)

dc.contributor.advisorŽivković, Vladimir
dc.contributor.otherJakovljević, Vladimir
dc.contributor.otherĐurić, Dragan
dc.contributor.otherSrejović, Ivan
dc.creatorKornjača, Duško
dc.date.accessioned2018-05-19T12:38:36Z
dc.date.available2018-05-19T12:38:36Z
dc.date.available2020-07-03T15:20:05Z
dc.date.issued2018-02-23
dc.identifier.urihttp://eteze.kg.ac.rs/application/showtheses?thesesId=5761
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/9442
dc.identifier.urihttps://fedorakg.kg.ac.rs/fedora/get/o:970/bdef:Content/download
dc.description.abstractUvod: S obzirom na dokazano povećanje aktivnosti acetilholinesteraze (AchE) unutar centralnog nervnog sistema u uslovima hiperhomocisteinemije, postavlja se pretpostavka da li homocistein može i u srčanom mišiću da reguliše aktivnost ovog enzima. Povezanost metabolizma homocisteina, slobodnih radikala i gasotransmitera u okviru kardiovaskularnog sistema je još veoma slabo istražena. Takođe, vrlo je interesantno da u dostupnoj literaturi nema podataka o aktivnosti i eventualnoj ulozi AchE u funkciji srca, pogotovo u uslovima hiperhomocisteinemije. Cilj: Cilj ovog istraživanja je bilo ispitivanje efekata akutne (indukovane DL-homocisteinom i DL-homocistein tiolaktonom) i subhronične hiperhomocisteinemije (indukovane DL-homocisteinom) na koncentraciju prooksidativnih i aktivnost antioksidativnih markera u plazmi pacova, kao i na aktivnost enzima acetilholinesteraze u tkivu miokarda pacova. Materijal i metode: Istraživanje je dizajnirano kao eksperimentalna studija sprovedena in vitro i ex vivo. U cilju izazivanja akutne hiperhomocisteinemije eksperimentalnim grupama je intraperitonealno administrirana jedna doza DL-homocisteina (8 mmol/kg tm) i DL-homocistein tiolaktona (8 mmol/kg tm). Šezdeset minuta nakon aplikacije, životinje su se žrtvovale radi prikupljanja uzoraka krvi (za merenje markera oksidacionog stresa) i uzimanja tkiva srca u čijem homogenatu se određivala aktivnost AchE. Subhronična hiperhomocisteinemija je izazvana aplikacijom DL-homocisteina (0.45 μmol/g tm. s.c., dva puta dnevno u intervalu od 8 sati, u periodu od četrnaest dana). Rezultati: Akutna i hronična hiperhomocisteinemija su povezane sa sniženjem aktivnosti acetilholinesteraze u srcu pacova. Ovi nalazi sugerišu da homocistein putem dejstva na AchE može da menja holinergičku kontrolu srčane funkcije odnosno da inhibicijom razgradnje acetilholina potencira snažniji i dugotrajniji negativni holinergički efekat na srce. Blokada produkcije NO i SO je bila povezana sa sniženjem aktivnosti acetilholinesteraze. Ova saznanja indikuju da NO i SO signalni putevi mogu da imaju ulogu u modulaciji aktivnosti ovog enzima. Na osnovu naših nalaza uočava se da je ovaj efekat bio najizraženiji u slučaju NO signalizacije. Redukcija srčane AchE aktivnosti pod uticajem homocisteina prelazi u značajan porast prilikom aplikacije inhibitora sinteze gasotransmitera. Na ovaj način potenciranje holinergičkih dejstava homocisteina u srcu ne samo da prestaje u uslovima odsustva delovanja gasotransmitera, već postaje smanjeno zahvaljujući pojačanoj razgradnji acetilholina. Zaključak: Dobijeni rezultati daju originalan i bitan doprinos u razumevanju uloge acetilholinesteraze u funkciji miokarda u uslovima hiperhomocisteinemije, kao i u uslovima smanjenja dostupnosti pojedinih gasotransmitera, čime se otvara niz mogućnosti za ispitivanje šire kliničke primene, imajući u vidu značaj homocisteina u nastanku patoloških entiteta kardiovaskularnog sistema.sr
dc.description.abstractIntroduction: Considering the proven increase in activity of acetylcholinesterase (AchE) within the central nervous system under conditions of hyperchomocysteinemia, it is assumed that homocysteine can also regulate the activity of this enzyme in the heart muscle. The association of metabolism of homocysteine, free radicals and gasotransmitters within the cardiovascular system is still very poorly investigated. It is also very interesting that in the available literature there is no information regarding the activity and the possible role of AchE in the function of the heart, especially in the conditions of hyperhomocysteinaemia. Aim: The aim of this study was to investigate the effects of acute (induced by DL-homocysteine and DL-homocysteine thiolactone) and subchronic hyperhomocysteinemia (induced by DL-homocysteine) on the concentration of prooxidative and activity of antioxidative markers in rat plasma as well as the activity of acetylcholinesterase enzymes in myocardial tissue rats. Material and methods: The research was designed as an experimental study conducted in vitro and ex vivo. In order to induce acute hyperchomocysteinemia to experimental groups, one dose of DL-homocysteine (8 mmol / kg tm) and DL-homocysteine thiolactone (8 mmol / kg tm) was administered intraperitoneally. Sixty minutes after application, animals were sacrificed to collect blood samples (for measuring oxidative stress markers) and heart tissue was taken in whose homogenate the AchE activity was determined. Subchronic hyperchomocysteinemia was caused by the application of DL-homocysteine (0.45 μmol / g of tm.s.c., twice daily for an interval of 8 hours, for a period of fourteen days). Results: Acute and chronic hyperchomocysteinemia were associated with a decrease in acetylcholinesterase activity in the heart of rats. These findings suggest that homocysteine can alter the cholinergic control of the cardiac function via the action on AchE, that is, by inhibiting the decomposition of acetylcholine, a stronger and longer-lasting negative cholinergic effect on the heart. Blockage of NO and CO production was associated with a decrease in acetylcholinesterase activity. These findings indicate that NO and CO signal pathways can play a role in modulation of the activity of this enzyme. Based on our findings, it can be noted that this effect was most pronounced in the case of NO signaling. Reduction of cardiac AchE activity under the influence of homocysteine transitions to a significant increase after application of gasotransmitter synthesis inhibitors. On this way, the potentiation of cholinergic effects of homocysteine in the heart not only stops under the conditions of absence of the action of the gasotransmitter, but becomes reduced due to the intensified degradation of acetylcholine. Conclusions: The obtained results give a novel and important contribution to understanding the role of acetylcholinesterase in the function of myocardium in the conditions of hyperhomocysteinemia, as well as in the conditions of reducing the availability of specific gasotransmitters, thus opening up a range of possibilities for testing wider clinical application, bearing in mind the significance of homocysteine in the onset of pathological entities of the cardiovascular system.en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Крагујевцу, Факултет медицинских наукаsr
dc.rightsopenAccessen
dc.sourceУниверзитет у Крагујевцуsr
dc.subjectacetilholinesterazasr
dc.subjectacetylcholinesteraseen
dc.subjectgasotransmiterisr
dc.subjectsrcesr
dc.subjectpacovsr
dc.subjecthomocisteinsr
dc.subjectgasotransmittersen
dc.subjecthearten
dc.subjectraten
dc.subjecthomocysteineen
dc.titleEfekti hiperhomocisteinemije na parametre oksidacionog stresa i aktivnost enzima acetilholinesteraze u plazmi i srcu pacova: uloga gasnih transmitera (NO, H2S i SO)sr
dc.title.alternativeEffects of hyperhomocysteinemia on parameters of oxidative stress and activity acetylcholinesterase enzyme in plasma and heart rats: the role of gasotransmitters (NO,H2S and СО)en
dc.typedoctoralThesis
dc.rights.licenseBY-NC-ND
dcterms.abstractЖивковић, Владимир; Срејовић, Иван; Јаковљевић, Владимир; Ђурић, Драган; Корњача, Душко; Ефекти хиперхомоцистеинемије на параметре оксидационог стреса и активност ензима ацетилхолинестеразе у плазми и срцу пацова: улога гасних трансмитера (НО, Х2С и СО); Ефекти хиперхомоцистеинемије на параметре оксидационог стреса и активност ензима ацетилхолинестеразе у плазми и срцу пацова: улога гасних трансмитера (НО, Х2С и СО);
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/50093/Izvestaj_Dusko_Kornjaca_Medicinski.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/50092/Disertacija.pdf


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