NAD levels in the rat primary cultured hepatocytes affected by peroxisome-proliferators

The effect of peroxisome-proliferators (PPs) on the NAD level in primary cultured rat hepatocytes was investigated and compared with that in the liver of rat administered with PPs. Various PPs, including fibrates, phthalate esters and steroid, increased NAD level in the cultured hepatocytes as in whole animal with a little exception. The NAD level decreased after once reaching the peak by the addition of most PPs. The gradual decrease of NAD observed in primary cultured hepatocytes, was partially inhibited by the addition of poly(ADP-ribose) polymerase and/or NAD glycohydrolase inhibitors. In the presence of these inhibitors, the increase of NAD by PPs still remained. The mechanism of increasing NAD level by PPs will be due to the stimulation of tryptophan (Trp)-NAD biosynthesis, with the possibility of the transcriptional regulation of genes related to Trp-NAD pathway by PPs. This in vitro system, therefore, can be used to clarify detailed mechanism of the stimulation of hepatic NAD biosynthesis in rats administered PPs.