Reversal of experimental acute hepatic failure in the rat

Abstract

A suitable animal model of acute fulminant hepatic failure was developed in the rat by the administration of the selective hepatotoxin, galactosamine hydrochloride. A dosage of 2.6 g/kg given intraperitoneally to Lewis rats resulted in reproducible, potentially reversible hepatic necrosis and high mortality. The ability of dispersed single-cell suspensions of syngeneic hepatocytes, allogeneic hepatocytes, and bone marrow to provide “support” so that liver recovery could occur was explored in this model. Syngeneic hepatocytes (4 × 10 7 cells) given intraperitoneally 48 and 60 hr after toxin administration increased survival to 70 and 66%, respectively, compared to a control of 0%. Hepatocytes prepared from Fischer strain animals which differ from Lewis strain at minor histocompatibility loci similarly improved survival (62.5%). Syngeneic bone marrow cells (4 × 10 7 cells) given intraperitoneally 24 hr after toxin administration improved survival to 62.5% compared to a control group of 0%. This effect is not mediated by a mature macrophage or lymphoid cell population, but is specific to the cells derived from bone marrow, since single-cell suspensions of splenocytes, thymocytes, and peritoneal exudate cells had no effect on increasing survival. The mechanism of action of hepatocytes and bone marrow cells and whether they act by the same or different mechanisms remain to be defined. Cellular transplantation may offer a new simple measure in the treatment of acute hepatic failure.