Alkole Bağlı Olmayan Karaciğer Yağlanması Tedavisinde Nano-Enkapsüle İlaçların Etkinliğinin Lc/Q-Tof Ms ile Gerçekleştirilen Metabolomik ve Lipidomik Çalışmalarla İn Vitro Değerlendirilmesi

Abstract

In this thesis, the efficacy of vitamin E loaded nanoparticles developed using Human Serum Albumin (ISA) nanoparticles in the treatment of non-alcoholic fatty liver disease (NAFLD) was investigated by LC/Q-TOF MS-based metabolomics studies. To this end; blank NSA nanoparticles (Group C), vitamin E loaded nanoparticles (Group T) and vitamin E were applied to HEPG2 liver cancer cell lines. The cytosolic fractions obtained for all three groups (Groups C, T and E) were extracted with apolar/polar phase mixture. Obtained metabolite and lipid fractions were analyzed using the LC/QTOF MS instrument using a gradient elution program with a C18 column. The obtained raw chromatograms were subjected to up-to-date data processing processes in order to profile the highest number of metabolites and lipids. The detected peaks were normalized and the differences between the groups were examined. As a result of principal component analysis, it was observed that the metabolite and lipid profiles for the groups were different from each other. The 1969 peak data processing result detected in metabolomic studies was reduced to 247 peaks, which were statistically (p<0.05) different between the groups and differed at least 1.5 times. 44 metabolites matching with 18 of these peaks were examined. Differentiating metabolite and lipid profiles were interpreted and the advantages and disadvantages of using nanoencapsulated E vitamin were evaluated.