Membrane bioreactor using pig hepatocytes for in vitro evaluation of anti-inflammatory drugs

Membrane bioreactor using isolated hepatocytes is a good system for in vitro studies of cell drug metabolism. In this system cells are cultured on modified polyethersulfone membrane under homogeneous, stable and three-dimensional conditions in a similar in vivo microenvironment. The aim of this study was to evaluate liver specific functions of pig hepatocytes cultured in the bioreactor at increasing drug concentration of rofecoxib. Rofecoxib is a potent and highly inhibitor of cyclooxygenase-2 (COX-2), an inducible isoform of cyclooxygenase that plays a key role in inflammatory processes. The bioreactor performance was evaluated by assessing the ability of liver cells to eliminate rofecoxib. Biochemical activity of cells was assessed in terms of urea and albumin synthesis. Pig liver cells cultured in the membrane bioreactor exhibited viability and liver specific functions at higher levels than those of cells cultured in batch systems. The rate of rofecoxib elimination by cells increased with increasing rofecoxib concentration in the range 0-400 nM. Hepatocytes exhibited highest rates of albumin production and urea synthesis at 300-400 nM rofecoxib concentration.