Inhibition of ureogenesis in isolated rat liver cells by a non-steroidal anti-inflammatory drug (butibufen)

Abstract

The effect of a non-steroidal anti-inflammatory drug (butibufen) on ureogenesis in isolated rat hepatocytes has been studied. Butibufen at 0.4 mM, and particularly at 2 mM, strongly inhibited urea synthesis. The drug at these concentrations also inhibited markedly carbomoylphosphate synthetase activity. In addition, 2 mM butibufen lowered ATP concentrations of the cells and enhanced oxygen consumption in isolated liver mitochondria. The results suggest that the inhibition by 0.4 mM butibufen on carbamoylphosphate synthetase activity can account for the entire inhibition of ureogenesis, whereas the decreased cellular ATP concentration at 2 mM butibufen might be at least partly responsible for low carbamoylphosphate synthesis and thus, for reduced urea production. The decrease in ATP levels probably results from uncoupling effects of butibufen on oxidative phosphorylation.