The effect of catabolite concentration on the viability and functions of isolated rat hepatocytes.
The treatment of patients with hepatic failure by means of hybrid liver support devices using primary xenogeneic hepatocytes is currently hindered by the rapid loss of cell metabolic functions. Similarly to what happens with other mammalian cells, accumulation of catabolites in the neighborhood of cultured hepatocytes might significantly affect their viability and functions. In this paper, we investigated the effects of high concentrations of catabolites, such as ammonia and lactic acid, on the viability and functions of rat hepatocytes cultured on collagen coated Petri dishes. The effects on hepatocyte functions were established with respect to their ability to synthesize urea and to eliminate ammonia. Indeed, high catabolite concentrations effected both hepatocyte viability and functions. The number of viable hepatocytes decreased with increasing ammonia concentrations in the culture medium. High ammonia concentrations had also both an inhibitory and a toxic effect on hepatocyte functions. In fact, the hepatocytes synthesized urea and 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.
Catapano
G
G
Department of Chemical and Materials Engineering, University of Calabria, Arcavacata di Rende (CS), Italy.
De Bartolo
L
L
Lombardi
C P
CP
Drioli
E
E
D000641:Ammonia / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D007773:Lactates / Q000633:toxicity*; D019344:Lactic Acid; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008115:Liver Regeneration; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014508:Urea / Q000378:metabolism
D007773:Lactates; D019344:Lactic Acid; D000641:Ammonia; D014508:Urea; D003094:Collagen; D005969:Glutamate Dehydrogenase