engleski

ASSESSMENT OF HEPATOSTEATOGENIC EFFECTS IN CELL CULTURE MODEL OF DRUG INDUCED FATTY LIVER DISEASE

Introduction: Toxicity represents one of the major obstacles to drug development and reasons for drug withdrawal from the market, with emphasis on drug- induced liver injury (DILI), as being one of the most often toxicity incidences. Therefore, the pharmaceutical industry is still in need to predict hepatotoxicity in vitro. So far, various hepatic cell models have been developed in order to better understand drug metabolism and toxicity. In our study, we focused on a specific form of DILI- drug induced fatty liver disease (DIFLD). The aim of this study was to assess the effect of two known hepatotoxic drugs amiodarone and tamoxifen on cell survival and formation of lipid vesicles in HuH7 cell line. Materials and Methods: HuH7 cells were incubated with 5 μM to 20 μM concentrations of amiodarone and tamoxifen, respectively. Cell viability was estimated after 24h, 48h and 72h of exposure to the drugs by MTT assay. Changes in cell shape, formation of lipid droplets and the extent of steatosis were evaluated by fluorescent microscopy after Oil-Red- O and DAPI staining, respectively. Results:The decrease in cell survival with increasing concentrations of drugs was observed by MTT assay, with slightly greater decrease demonstrated in amiodarone-treated cells. Appearance of the cells also changed: increased number of lipid vesicles, positioned on the inner side of the cell membrane, however displacement of the nucleus was not detected. Conclusion: Consistent with other studies, our results also confirmed the steatogenic and apoptogenic effect of amiodarone and tamoxifen. In order to better understand and possibly prevent hepatotoxic effect of these drugs, further research is required.

drug induced liver injury ; amiodarone ; tamoxifen

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