Comparison of hepatocyte cultures and liver slices in in vitro toxicity testing

The aim of this study was to compare the in vitro toxicities of two hepatot oxins in hepatocyte cultures and in liver slices from both rats and dogs. H epatocytes and liver slices were pre-incubated for 2 hours and then exposed to galactosamine or paracetamol, both of which mainly induce liver necrosi s in vivo. Following exposure to the compounds for 20 hours, neutral red up take (NRU [hepatocyte cultures only]), MTT reduction, and reduced glutathio ne (GSH), adenosine triphosphate (ATP) and protein content, were used to me asure the toxicity induced. In general, galactosamine and paracetamol expos ure caused comparable levels of toxicity in hepatocyte cultures and in live r slices. For galactosamine, no consistent differences were seen between he patocyte cultures and liver slices. With paracetamol, the toxic effects wer e generally slightly more pronounced in hepatocyte cultures than in liver s lices, and the preparations from dog liver were more sensitive than those f rom rat liver to paracetamol exposure. These results are in agreement with previously described species differences in vitro. NRU and GSH content were more sensitive and more consistent endpoints than MTT reduction, ATP conte nt or protein content. Liver slices appeared to lose viability over the 20 hours in culture. Therefore, it can be concluded that liver slices should o nly be used in relatively short-term investigations.