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Interference of the free thiol group of disulfiram metabolite and glutathione response to oxidative stress induced with cadmium and/or alcohol in the liver of wistar rats

dc.contributor.advisorĐukić, Mirjana
dc.contributor.otherNinković, Milica
dc.contributor.otherVujanović, Dragana
dc.contributor.otherĐukić-Ćosić, Danijela
dc.contributor.otherSimić, Milena
dc.creatorBegić, Aida
dc.date.accessioned2017-07-28T14:35:34Z
dc.date.available2017-07-28T14:35:34Z
dc.date.available2020-07-03T09:47:26Z
dc.date.issued2017-06-15
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=5163
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/8460
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:16020/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=49205263
dc.description.abstractMehanizmi hepatotoksičnog efekta individualne i paralelne izloženosti organizma kadmijumu (Cd) i/ili etanolu su dovoljno ispitani, dok efekti disulfirama (DSF) na jetru nakon prethodne izloženosti organizma Cd i/ili etanolu, kao i tokom koekspozicije sa Cd, nisu istraženi. Imajući u vidu da je duvanski dim značajan izvor izloženosti Cd, zatim, da su alkoholičari uglavnom i pušači, te da je averzivna terapija DSF dio realnog scenarija liječenja alkoholizma, cilj ove studije je bio da se ispitaju efekti individualne izloženosti DSF na redoks status (posebno u domenu glutationskog ciklusa), status esencijalnih metala i funkciju jetre, kao i na status jetre nakon prethodne izloženosti organizma Cd i/ili etanolu, kao i tokom koekspozicije sa Cd, iz razloga što ovi pacijenti nastavljaju sa pušenjem cigareta tokom terapije DSF, dok je unos alkohola ukinut. Rasvjetljavanje interferencije sulfhidrilne (–SH) grupe metabolita DSF sa antioksidativnim odgovorom glutationskog ciklusa, kao i statusom metala u jetri u datim eksperimentalnim uslovima bio je fokus ovog istraživanja, što je od značaja ako uzmemo u obzir da i Cd i etanol, kao i izmijenjeni status esencijalnih metala remete redoks metabolizam, odnosno mijenjaju glutationski status u jetri. Analitika simultanog određivanja redukovanog i oksidovanog oblika glutationa (GSH i GSSG) iz homogenata jetre tretiranih pacova, primjenom visoko efikasne tečne hromatografije uz UV detekciju (HPLC-UV), bio je dodatni cilj ove disertacije. Sprovedena animalna studija (na pacovima Wistar soja, mužjacima, n = 210) imala je za cilj da imitira okolnosti alkoholičara-pušača prije i tokom primjene DSF i trajala je za pojedine eksperimentalne grupe 21, odnosno 42 dana. Etanol, DSF i maslinovo ulje (OlO) kao rastvarač za DSF, su davani oralnim putem (gavažom), a Cd intraperitonelano, na dnevnoj bazi. Oformljene eksperimentalne, kao i kontrolne grupe imala su podgrupe, shodno terminima žrtvovanja pacova (1, 3, 10, 21 i 42 dana), navedenih u u subskriptu, i činilo ih je po 6 pacova: tri kontrolne grupe (C1-42, OlO1-21 i OlO22-42); tri grupe koje su individualno bile izložene ispitivanim agensima (A1-21, Cd1-42 i DSF1-21); i četiri grupe koje su bile paralelno izložene ispitivanim agesnima (A1-21/Cd1-21, A1-21/DSF22-42, Cd1-42/DSF22-42 i A1-21/Cd1-42/DSF22-42)...sr
dc.description.abstractMechanisms involved in genesis of hepatotoxic effects following individual and parallel exposure to cadmium (Cd) and/or ethanol, are thoroughly investigated. However, the effects of disulfiram (DSF) introduced to treatment following exposure to Cd and/or ethanol were not formerly presented in studies. While conducting the study it was taken into consideration that cigarette smoke is a significant source of Cd exposure, as well as that alcoholics are most likely smokers, and also that aversive therapy with DSF is a real life scenario in alcohol dependence treatment. The aim of the study was to investigate the effects of individual exposure to DSF related to redox status (particularly in domain of glutathione cycle), essential metals status and liver function, as well as the status following exposure to Cd and/or ethanol and also during co-exposure with Cd, considering that patients undergoing DSF treatment continue with heavy smoking, whilst alcohol intake is excluded. The focus of the study was set on elucidation of possible interference of the free thiol (–SH) group of DSF metabolite and antioxidant glutathione response, as well as essential metals status under specified experimental conditions. Additionally, Cd and ethanol, along with changed essential metals status affect glutathione homeostasis in the liver. Both glutathione forms, reduced and oxidized (GSH and GSSG), were measured by high performance liquid chromatography method with UV detection (HPLC-UV). The conducted animal study (male Wistar rats, n = 210) aimed to mimic circumstances in the liver of alcoholics-smokers before and during DSF treatment, with defined duration of 21 or 42 days for different experimental groups. Ethanol, DSF and olive oil (OlO), used as DSF solvent, were daily administered orally (via gavage), whilst Cd was administered intraperitoneally. Each of defined experimental and control groups was divided, according to the chosen time of exposure (1, 3, 10, 21 and 42 days), in subgroups (specified in subscript) constituted of 6 rats: three control groups (C1-42, OlO1-21 and OlO22-42;); three groups individually exposed to investigated agents (A1-21, Cd1-42 and DSF1-21); and four groups with parallel exposure to investigated agents (A1-21/Cd1-21, A1-21/DSF22-42, Cd1-42/DSF22-42 and A1-21/Cd1-42/DSF22-42)...en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Фармацеутски факултетsr
dc.rightsopenAccessen
dc.sourceУниверзитет у Београдуsr
dc.subjectkadmijumsr
dc.subjectcadmiumen
dc.subjectethanolen
dc.subjectdisulfiramen
dc.subjectoxidative stressen
dc.subjectesential bioelementsen
dc.subjectglutathione cycleen
dc.subjectliveren
dc.subjectWistar ratsen
dc.subjectetanolsr
dc.subjectdisulfiramsr
dc.subjectoksidativni stressr
dc.subjectglutationski ciklussr
dc.subjectesencijalni bioelementisr
dc.subjectjetrasr
dc.subjectWistar pacovsr
dc.titleInterferencija tiolnih grupa metabolita disulfirama sa glutationskim odgovorom na oksidativni stres indukovan kadmijujoj i/ili alkoholom u jetri pacovasr
dc.title.alternativeInterference of the free thiol group of disulfiram metabolite and glutathione response to oxidative stress induced with cadmium and/or alcohol in the liver of wistar ratsen
dc.typedoctoralThesis
dc.rights.licenseBY-NC-ND
dcterms.abstractЂукић, Мирјана; Нинковић, Милица; Вујановић, Драгана; Ђукић-Ћосић, Данијела; Симић, Милена; Бегић, Aида; Интерференција тиолних група метаболита дисулфирама са глутатионским одговором на оксидативни стрес индукован кадмијујој и/или алкохолом у јетри пацова; Интерференција тиолних група метаболита дисулфирама са глутатионским одговором на оксидативни стрес индукован кадмијујој и/или алкохолом у јетри пацова;
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/24177/IzvestajKomisije11148.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/24176/Disertacija.pdf


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