EFFECTS OF NICOTINAMIDE ON HEPATOCYTE VIABILITY AND SECRETION OF ALBUMIN AND ALPHA(1)-ACID GLYCOPROTEIN BY ADULT-RAT HEPATOCYTES IN PRIMOCULTURE - COMPARISON WITH DEXAMETHASONE AND RECOMBINANT HUMAN INTERLEUKIN-6

The effects of nicotinamide on hepatocyte viability and secretion of albumin and alpha(1)-acid glycoprotein were studied in the absence or presence of dexamethasone and/or recombinant human interleukin-6 either after cell attachment (2 h) or after 24, 48, and 72 h of culture. The evolution of hepatocyte survival during the culture was appreciated by measurement of total DNA content. The secretion of albumin and alpha(1)-acid glycoprotein was measured after a 4-h period following cell attachment or after 24, 48 and 72 h of culture. The important decrease of DNA content, mRNA levels and secretion of albumin and alpha(1)-acid glycoprotein in control cultures after 2-3 days was not prevented by the addition of nicotinamide. In contrast, dexamethasone alone or with recombinant human interleukin-6 improved DNA content and albumin secretion with no additional effect of nicotinamide. The secretion of alpha(1)-acid glycoprotein was largely induced by dexamethasone alone or dexamethasone and recombinant human interleukin-6. The increase of alpha(1)-acid glycoprotein secretion was not modified by the addition of nicotinamide and averaged respectively 27- and 60-fold for dexamethasone alone and dexamethasone and recombinant human interleukin-6 after 48 h. These observations suggested that nicotinamide, at least in the conditions tested here, is unable to prevent alterations of hepatocyte viability and gene expression of cultured hepatocytes.