Use of hepatocyte co-cultures in the assessment of drug toxicity from chronic exposure

Abstract

1. In rat hepatocyte cultures, clonidine and malotilate were cytotoxic at 170 μM but did not induce changes at lower concentrations during 24 h exposure. Amitriptyline induced cell injury at 20 μM but was ineffective at 2 μM.

2. In co-culture of rat or human hepatocytes with rat liver epithelial cells. 2 μM imitriptyline was cytotoxic after 7 days treatment whereas 70 to 100 μM clonidine or malotilate gave no significant effect.

3. These results suggest that co-cultured hepatocytes which retain their differentiated state for several days or weeks, represent a promising tool for studying hepatotoxicity from chronic treatment in vitro.