Abstract
Pharmacometabolomics is a novel metabolomics tool to provide information about how a subject will respond to drug treatment in metabolome level. In this study, a Q-TOF LC/MS based untargeted metabolomics approach was performed to evaluate the metabolomic profile change on HepG2 hepatocellular carcinoma cells treated with vitamin E in free form, vitamin E loaded in human serum albumin nanoparticles, and blank nanoparticles.Vitamin E loaded human serum albumin nanoparticles, and blank nanoparticles were prepared and characterized with particle size distribution, surface charge and cytotoxicity against L929 and HepG2 cell lines. The metabolite and lipid fractions of the cells treated with vitamin E, vitamin E loaded human serum albumin nanoparticles, and blank nanoparticles were analyzed using Q-TOF LC/MS. XCMS and MetaboAnalyst 5.0 were used to process the data and identify the peaks. Principal component analysis (PCA) was performed to visualize the differences between groups.Totally 247 peaks for metabolites and 788 peaks for lipid were found to be statistically in different ratios (p < 0.05 and fold change >1.5) between groups. Some metabolites (histidine, aspartylglycosamine, glutathione, prostaglandin, alpha-tocotrienol, urobilinogen, coproporphyrinogen, and glucosylceramide) involved in liver activity and/or known as diagnostic and prognostic biomarker(s) were the effected ones upon Vitamin E treatment.The metabolomic profiles for vitamin E loaded human serum albumin nanoparticles treated cells were different than the ones treated with vitamin E alone. This study concluded that both vitamin E and vitamin E loaded human serum albumin nanoparticles may provide effects on liver regeneration pathways but with different responses. According to the results in the present study, it can be considered that the pharmacometabolomics profile of the nanoparticle-based drug delivery for vitamin E can be different in clinical practice.
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