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doctoral thesis
Utjecaj analoga peptida 1 sličnog glukagonu na mehanizme nastanka lijekovima izazvanog jetrenog oštećenja u staničnim kulturama
2022. urn:nbn:hr:152:881540
Omanović Kolarić, Tea
Josip Juraj Strossmayer University of Osijek
Faculty of Medicine Osijek

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Omanović Kolarić, T. (2022). Utjecaj analoga peptida 1 sličnog glukagonu na mehanizme nastanka lijekovima izazvanog jetrenog oštećenja u staničnim kulturama (Doctoral thesis). Osijek: Josip Juraj Strossmayer University of Osijek, Faculty of Medicine Osijek. Retrieved from https://urn.nsk.hr/urn:nbn:hr:152:881540

Omanović Kolarić, Tea. "Utjecaj analoga peptida 1 sličnog glukagonu na mehanizme nastanka lijekovima izazvanog jetrenog oštećenja u staničnim kulturama." Doctoral thesis, Josip Juraj Strossmayer University of Osijek, Faculty of Medicine Osijek, 2022. https://urn.nsk.hr/urn:nbn:hr:152:881540

Omanović Kolarić, Tea. "Utjecaj analoga peptida 1 sličnog glukagonu na mehanizme nastanka lijekovima izazvanog jetrenog oštećenja u staničnim kulturama." Doctoral thesis, Josip Juraj Strossmayer University of Osijek, Faculty of Medicine Osijek, 2022. https://urn.nsk.hr/urn:nbn:hr:152:881540

Omanović Kolarić, T. (2022). 'Utjecaj analoga peptida 1 sličnog glukagonu na mehanizme nastanka lijekovima izazvanog jetrenog oštećenja u staničnim kulturama', Doctoral thesis, Josip Juraj Strossmayer University of Osijek, Faculty of Medicine Osijek, accessed 09 April 2025, https://urn.nsk.hr/urn:nbn:hr:152:881540

Omanović Kolarić T. Utjecaj analoga peptida 1 sličnog glukagonu na mehanizme nastanka lijekovima izazvanog jetrenog oštećenja u staničnim kulturama [Doctoral thesis]. Osijek: Josip Juraj Strossmayer University of Osijek, Faculty of Medicine Osijek; 2022 [cited 2025 April 09] Available at: https://urn.nsk.hr/urn:nbn:hr:152:881540

T. Omanović Kolarić, "Utjecaj analoga peptida 1 sličnog glukagonu na mehanizme nastanka lijekovima izazvanog jetrenog oštećenja u staničnim kulturama", Doctoral thesis, Josip Juraj Strossmayer University of Osijek, Faculty of Medicine Osijek, Osijek, 2022. Available at: https://urn.nsk.hr/urn:nbn:hr:152:881540

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TitleUtjecaj analoga peptida 1 sličnog glukagonu na mehanizme nastanka lijekovima izazvanog jetrenog oštećenja u staničnim kulturama
Title (english)Effect of GLP-1 analogs on the pathophysiological mechanisms of drug-induced liver injury in cell cultures
AuthorTea Omanović Kolarić
MentorMartina Smolić (mentor)
Committee memberMario Štefanić (predsjednik povjerenstva)
GranterJosip Juraj Strossmayer University of Osijek
Faculty of Medicine Osijek
Osijek
Defense date and country2022-09-30, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Pharmacology
Universal decimal classification
(UDC)		61 - Medical sciences
Abstract
Uvod i ciljevi istraživanja: Masna promjena jetre izazvana lijekovima (DIFLD) postala je čest uzrok nealkoholne masne promjene jetre (NAFLD). zbog starenja stanovništva i raširenosti polifarmacije u starijih osoba. Moguće je da NAFLD i DIFLD koegzistiraju, što čini njihovo razlikovanje još važnijim. Naš je cilj bio istražiti modele NAFLD i DIFLD steatoze hepatocita u staničnoj kulturi i utvrditi učinke liraglutida u tim modelima. Materijali i metode: Za izradu modela steatoze hepatocita NAFLD i... More DIFLD, Huh7 stanice su tretirane oleinskom kiselinom, amiodaronom ili tamoksifenom. Liraglutid je dodan kao kotretman u stanice, a MTT je korišten za mjerenje viabilnosti stanica, dok je test isključenja eritrozin B bojom korišten za potvrdu rezultata za preživljavanje stanica. Oil-Red-O bojenje i test triglicerida korišteni su za mjerenje nakupljanja lipida, GSH kit korišten je za mjerenje koncentracija GSH u sva tri modela, a RT-PCR je korišten za mjerenje intracelularnih signala uključenih u hepatosteatozu. Rezultati: Koncentracije oleinske kiseline, amiodarona i tamoksifena koje su postigle 80% vijabilnosti stanica u usporedbi s negativnom kontrolom korištene su u narednim eksperimentima za uspostavljanje NAFLD i DIFLD modela. Te su koncentracije bile: 0,5 mM oleinske kiseline, 20 µM amiodarona, odnosno 2 µM tamoksifena. Liraglutid je poboljšao vijabilnost stanica u svim modelima (p < 0,01). Svi modeli pokazali su povećanu akumulaciju lipida, pri čemu je DIFLD pokazao mikrosteatotsku sliku, a NAFLD makrosteatotsku sliku, od kojih potonji odgovara većoj akumulaciji triglicerida. Liraglutid je smanjio ove steatotične promjene (p < 0,001). Razine GSH bile su smanjene u sva tri modela steatoze. Amiodaron i tamoksifen smanjili su ga na 80% u usporedbi s DMEM negativnom kontrolom (p < 0,01, p < 0,05), dok je učinak OA bio manji. Nije bilo značajne razlike u koncentracijama GSH s kotretmanom LIRA-om. U NAFLD i DIFLD modelu steatoze hepatocita, liraglutid je smanjio ekspresiju lipogenih puteva ACSL1, PPARG i SREBF1 (p < 0,01). Zaključak: U NAFLD i DIFLD modelima steatoze hepatocita uspostavljenim s Huh7 staničnom kulturom, liraglutid je smanjio steatozu hepatocita kroz regulaciju lipogenih puteva ACSL1, PPARG i SREBF1. Less
Abstract (english)
Background and aims: Drug-induced fatty liver disease (DIFLD) has become a common cause of non-alcoholic fatty liver disease (NAFLD) due to the aging of the population and the prevalence of polypharmacy in the elderly. It is possible for NAFLD and DIFLD to coexist which makes it even more crucial to be able to differentiate them. Our aim was to investigate hepatocyte steatosis NAFLD and DIFLD cell culture models and ascertain the effects of liraglutide in those models. Materials and Methods:... More To create models of hepatocyte steatosis NAFLD and DIFLD, Huh7 cells were treated with oleic acid, amiodarone, or tamoxifen. Liraglutide was administered to the cells, and MTT was used to measure cell viability, while Erythrosin B color exclusion test was used to confirm results for cell survival. Oil-Red-O staining and a triglyceride assay were used to measure lipid accumulation, GSH assay kit was used for the measurement of GSH concentrations in all three models, and RT-PCR was used to measure intracellular signals involved in hepatosteatosis. Results: The concentrations of oleic acid, amiodarone, and tamoxifen that achieved 80% cell viability comparing to the negative control were used in subsequent experiments to establish the NAFLD and DIFLD models. Those were 0.5 mM oleic acid, 20 µM amiodarone, and 2 µM tamoxifen, respectively. Liraglutide improved cell viability in all models (p < 0,01). All models showed increased lipid accumulation, with DIFLD showing a microsteatotic pattern and NAFLD showing a macrosteatotic pattern, the latter of which corresponds to greater triglyceride accumulation. These steatotic changes were lessened by liraglutide (p < 0,001). GSH levels were reduced in all three models of steatosis. Amiodarone and tamoxifen reduced it to 80% compared to DMEM negative control (p < 0,01, p < 0,05), while effect of OA was smaller. There was no significant difference in GSH concentrations with liraglutide co-treatment. In the hepatocyte steatosis NAFLD and DIFLD models, liraglutide decreased the expression of the lipogenic ACSL1, PPARG, and SREBF1 pathways (p < 0,01). Conclusion: In hepatocyte steatosis NAFLD and DIFLD models established with Huh7 cell culture, liraglutide reduced hepatocyte steatosis through downregulation of lipogenic ACSL1, PPARG, and SREBF1 pathways. Less
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:152:881540
Promotion2022
Study programmeTitle: University Postgraduate Study
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2022-12-14 09:45:39
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