Protective effect of nafamostat mesilate on injury of porcine hepatocytes by human plasma

Nafamostat mesilate (NM), a protease inhibitor, possesses a cytoprotective effect and inhibits the activation of complement. The present study investi gated whether NM has any protective effect against injury of porcine hepato cytes by human plasma in a bioartificial liver support system. Porcine hepa tocytes were harvested and seeded at a density of 2 x 10(5) cells on a 35-m m collagen-coated plate in Dulbecco's modified Eagle's medium (DMEM) with 1 0% fetal calf serum. Twenty-four hours later, the medium was replaced with human plasma with three concentrations of NM between 3.8 x 10(-5) and 3.8 x 10(-4) M and then cultured for 6 h. The viability of porcine hepatocytes, lactate dehydrogenase (LDH) levels, lidocaine clearance, porcine albumin pr oduction, and changes in complement (C3) levels were measured. The viabilit y of porcine hepatocytes in human plasma decreased significantly to 37.7 +/ - 11.4% of that in DMEM. NM improved the viability of the hepatocytes, lowe red the levels of LDH, and increased lidocaine clearance and albumin produc tion in a concentration-dependent manner. The concentrations of C3, the mar ker of xenogeneic reactions, did not change significantly, indicating that no hyperacute xenogeneic reaction occurred in our series. Together, our res ults suggested that NM exerts favorable effects on porcine hepatocytes in h uman plasma through direct effect such as prevention of protease activity i n the plasma membrane of porcine hepatocytes rather than inhibition of comp lement-dependent immunoreactions.