Research On The Feasibility Of Tissue-like Cultured Hepatocytes In Drug Screening

In this paper, we studied the feasibility of the hepatocytes culture model by gel entrapment in researching on drug metabolism and drug hepatotoxicities.First, we had detected the enzyme activity of CYP1A2, CYP2B, CYP3A and GST of hepatocytes cultured in both gel entrapment and monolayer. By comparison of enzyme activitys in gel entrapment and monolayer culture, it was concluded that cells of gel entrapment can maintain these enzyme activity better than those of monolayer.Secondly, in aim to find a way of preserving hepatocytes, we cryopreservated the hepatocytes and then detected the enzyme activity of cryopreservated cells in both gel entrapment and monolayer. Cryopreservated cells could be cultured by both gel entrapment and monolayers.We also evaluated hepatotoxity of tacrine by using gel entrapment culture in comparison with those of monolayer. Some new findings on mechanism of tacrine-induced hepatotoxicity were obtained by gel entrapment culture of hepatocytes, which facilitate to illustrate the controversial results about hepatotoxity of tacrine.Last, we used human hepatocytes to re-evaluate the enzyme activity and hepatotoxity of tacrine. It seemed that human hepatocytes had a less sensitivity to tacrine treatment than rat hepatocytes.In a word, gel entrapment culture is closer to the in vivo environment which may make it more appropriate in the research of drug metabolism and drug toxicity than monolayer culture.