Carbohydrate and lipid metabolism
HepaRG™ cells display glucose and insulin responsiveness and can be used to investigate carbohydrate homeostasis and lipogenesis.
Reactive metabolites
The stable and high levels of DMEs in HepaRG™ cells make them ideal for long-term and repeated dose toxicity studies in which a compound may be bioactivated and/or cause latent effects over days or weeks.
Steatosis
The accumulation triglycerides in HepaRG™ cells is predictive of the in-vivo steatosis reported in patients chronically treated with steatogenic drugs. Lipid accumulation directly correlates with levels of mRNA encoding for lipid synthesis markers, thus this toxicity can be monitored visually and at the gene level.
Phospholipidosis
HepaRG™ cells can be used to discriminate between drugs which cause steatosis (after 24 h) and phospholipidosis (evident after 2 weeks) e.g. amiodarone; and those which cause steatosis only e.g. tetracycline.
Cholestasis
Cholestatic drugs (via direct inhibition or down-regulation) can be identified by measuring their effects on bile acid efflux in HepaRG™ cells.
Genotoxicity and carcinogenicity
Since HepaRG™ cells have a good metabolic capacity and proliferative capacity, they can be implemented into the micronucleus test (MNT), as recommended by ECVAM and IWGT workshops. Whole genome expression analysis of HepaRG™ cells can discriminate between genotoxic and non-genotoxic compounds and provide information on compound- and time-dependent effects on cell cycle and apoptosis signalling pathways.
Mitochondrial toxicology
Apoptosis
Inflammation
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