engleski

In vitro assessment of molecular mechanisms of free fatty acids-induced and drugs-induced fatty liver disease

Background and Aims: In most obese patients one of the forms of NAFLD (non-alcoholic fatty liver disease) is present, consequently increasing the risk of hepatotoxicity of different drugs. Obese patients are more likely to be exposed to different types of pharmaceuticals, therefore, drug-induced liver disease in this group of patients is becoming one of the major issues. Additionally, various drugs are capable to induce fatty liver disease (DIFLD) even if preexisting fatty liver is not present. Nevertheless, the exact type of steatosis and molecular mechanisms of DIFLD are yet not fully enlightened. Therefore, the aim of our study was to evaluate molecular mechanisms involved in development of DIFLD and free fatty-acids-induced NAFLD in vitro. Materials and Methods: HuH7 cell line was used as a model of NAFLD and DIFLD. Cells were exposed to different concentrations of oleic (OA) and palmitic acid (PA) and known hepatotoxic drugs amiodarone and tamoxifen, respectively. After 48 hours, the extent of steatosis, apoptosis and lipogenic pathway’ genes expression was evaluated by Oil-Red-O and DAPI staining, MTT and PCR, respectively. Results: The number and size of lipid droplets in FAs and drugs-treated cells compared to controls were enlarged. The number of cells decreased with increasing concentrations of drugs and FAs, unlike the mRNA expression of PPARγ and SREBP-1 which was upregulated. Conclusion: A better understanding of molecular mechanisms underlying DIFLD development and progression, especially in obese patients with preexisting NAFLD is necessary in order to hamper progression of fatty liver disease to drug induced steatohepatitis.

NAFLD, DIFLD, amiodarone, tammoxifen

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