Assessment of therapeutic effect of liraglutide in newly established cell culture model of non- alcoholic and drug-induced fatty liver disease (CROSBI ID 721168)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija
Podaci o odgovornosti
Omanovic Kolaric, Tea ; Nincevic, V ; Kizivat, Tomislav ; Zjalic, Milorad ; Kuna, Lucija ; Bilic- Curcic, Ines ; Smolic, Martina
engleski
Assessment of therapeutic effect of liraglutide in newly established cell culture model of non- alcoholic and drug-induced fatty liver disease
Background and aims: The impact of non-alcoholic fatty liver disease (NAFLD) on global health is becoming more significant with the growing incidence of obesity and drugs consumption. Therefore, more research is necessary in order to enlighten underlying pathophysiologic mechanisms for these conditions and possible therapeutic approaches. Aims of our study were to establish reliable in vitro models of non-alcoholic and drug-induced fatty liver disease (DIFLD) and also to investigate possible therapeutic solutions in these in vitro models. Method: HuH7 cell culture models of NAFLD and DIFLD were established by incubation of Huh7 cells with 0, 5 mM oleic acid (OA), 5 μM to 20 μM of amiodarone, 1 μM to 10 μM of tamoxifen for various time periods (24 h, 48 h), respectively. Cells where cotreated with 1 nM to 100 nM of liraglutide in order to assess its potential beneficial effect in fatty liver models. Cell viability was measured by MTT ((3- (4, 5-dimethylthiazol-2-yl)-2, 5- diphenyltetrazolium bromide) assay. Changes in cell shape and the extent of hepatosteatosis were assessed by fluorescent microscopy as shown in Figure. Cell nuclei were stained with Hoechst, and fat droplets were stained with Oil-Red-O. Trigliceryde (TG) accumulation was measured by TGO-PAP method and the results were read on the microplate reader. Results: Tamoxifen significantly reduced cell viability in a dosedependent manner after just 24 h treatment, compared to amiodarone and OA. Liraglutide co-treatment improved cell viability and the effect was greater after a longer period of treatment, especially in tamoxifen-treated cells for almost 30% (p <0, 05). Microscopic observations demonstrated microsteatosis as the predominant form of liver cell injury in this time period, with the greatest accumulation of fat in OA model. Accordingly, TG accumulation was highest in OA model, while liraglutide diminished TG accumulation in all three models. Conclusion: This newly established cellular Huh7 model of NAFLD and DIFLD could provide a new tool for further studies on these conditions. Nevertheless, further research is needed to better understand the onset of fatty liver changes, drug toxicity, and the possible role of liraglutide in their treatment.
Liraglutide ; non-alcoholic fatty liver disease ; amiodarone ; tamoxifen ; cell culture
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Podaci o prilogu
718-719.
2022.
objavljeno
10.1016/S0168-8278(22)01755-X
Podaci o matičnoj publikaciji
Journal of Hepatology
Angeli, Paolo
Elsevier
Podaci o skupu
International Liver Congress™ 2022
poster
22.06.2022-26.06.2022
London, Ujedinjeno Kraljevstvo