Trypsin inhibitor may increase the formation of GSH conjugates of potentially toxic reactive intermediates in isolated rat hepatocytes

Aims to investigate the effect of liver digestion enzymes on the formation of potentially toxic reactive intermediates in suspensions of isolated rat hepatocytes. Isolated hepatocytes are recognized as one of the most relevant and practical models in drug metabolism and toxicity studies. Several modifications of the original twostage collagenase perfusion technique (Seglen 1972) have been reported for the preparation of hepatocytes. However, there is little information on the effects of the liver digestion enzyme on glutathione (L-g-glutamyl-L-cysteinyl-glycine; GSH) conjugation of potentially reactive intermediates in isolated rat hepatocytes. Results indicate that the presence of trypsin inhibitor in the of isolated rat hepatocytes may increase the formation of GSH conjugates of potentially toxic reactive intermediates. This could have significant implications for the interpretation of metabolism data derived from hepatocytes in suspension.