Predictive in vitro cardiotoxicity and hepatotoxicity screening system using neonatal rat heart cells and rat hepatocytes

To establish a predictive in vitro cardiovascular toxicity and hepatotoxicity screening system, whole cells from the neonatal rat heart and rat hepatocytes were cultured with known cardiotoxic and hepatotoxic compounds and cytotoxicities were assessed. The heart cells were isolated from neonatal SD rats by enzyme digestion and cultured on type I collagen gel. After a several days of preculture, the cells were exposed to test compounds for 24 or 48 hr and LDH activity in the cells was measured. The hepatocytes were isolated from adult SD rats by in situ perfusion with collagenase and cultured in type I collagen-coated plates. After several hours of preculture, the cells were exposed to test compounds for 24 hr and LDH activity in the cells was measured. The IC50 values for cardiotoxic anthracyclines in rat neonatal heart cells showed very good correlation with in vivo cardiotoxic doses in rats. IC50 values for cardiotoxic anthracyclines were much lower in the heart cells than in the hepatocytes, and IC50 values for known hepatotoxic compounds were lower in the hepatocytes than in the heart cells. The ratio of IC50 values (heart cells/hepatocytes) would be a good predictor of cardiotoxic and hepatotoxic compounds.