THE EFFECT OF CATABOLITE CONCENTRATION ON THE VIABILITY AND FUNCTIONSOF ISOLATED RAT HEPATOCYTES

The treatment of patients with hepatic failure by means of hybrid live r support devices using primary xenogeneic hepatocytes is currently hi ndered by the rapid loss of cell metabolic functions. Similarly to wha t happens with other mammalian cells, accumulation of catabolites in t he neighborhood of cultured hepatocytes might significantly affect the ir viability and functions. In this paper, we investigated the effects of high concentrations of catabolites, such as ammonia and lactic aci d, on the viability and functions of rat hepatocytes cultured on colla gen coated Petri dishes. The effects on hepatocyte functions were esta blished with respect to their ability to synthesize urea and to elimin ate ammonia. Indeed, high catabolite concentrations effected both hepa tocyte viability and functions. The number of viable hepatocytes decre ased with increasing ammonia concentrations in the culture-medium. Hig h ammonia concentrations had also both an inhibitory and a toxic effec t on hepatocyte functions. In fact, the hepatocytes synthesized urea a nd eliminated ammonia at rates that decreased with increasing ammonia concentrations. Similarly, high lactic acid concentrations were toxic to the cells and also inhibited their synthetic functions.