Effect of various barbituric acid derivatives on survival of functional hepatocytes from adult rats in primary culture.

Eighteen barbituric acid (BA) derivatives and three structurally related chemicals (non-BA-derivatives) were tested for their potency in supporting survival of functional hepatocytes from adult rats in primary culture. Of the 18 BA derivatives, nine drugs showed excellent maintenance effect on hepatocyte survival and function. Although four BA derivatives were also effective, their potency was relatively lower. The remaining five BA derivatives and three structurally related chemicals exhibited no maintenance effect. Thus, a correlation was found between the BA derivative structure and the potency for supporting hepatocyte survival in primary culture. The dose response curves of hepatocyte survival were generally biphasic in shape, as a function of BA derivative concentration. The optimum concentrations for observing the morphological and biochemical effects of the BA derivatives differed from each other. The maintenance of hepatocytes was attained only in the continuous presence of the BA derivatives in the medium. The nine excellent BA derivatives efficiently prevented hepatocytes from morphological degeneration which was observed in the control cultures. The surviving hepatocytes in the presence of these BA derivatives showed higher albumin secretion and retained higher basal levels of tyrosine aminotransferase (TAT) activity for at least 2 weeks in primary culture, as compared with control. Furthermore, the addition of dexamethasone (10 microM) caused a 2- to 4-fold induction of TAT activity for at least 2-weeks in primary culture.