Factors effective in reducing rat mortality due to acute liver failure as induced by D-galactosamine poisoning

Mortality from D-galactosamine hydrochloride (D-GalN)-induced acute liver failure (ALF) in rats can be reduced by (1) transplanting intact hepatocytes; (2) injecting cytosol from fractionated hepatocytes dispersed from a liver subjected to 70% hepatectomy 24 hr earlier (CYT-H); (3) injecting a cell-free supernate derived from cultured hepatocytes (SUP); or (4) injecting neuraminidase-treated plasma where the plasma is drawn 24 hr after donor rats are subjected to 70% hepatectomy (PHP-neu). These treatments are effective when administered 20-24 hr after D-GalN poisoning, but experiments to determine the alterations in mortality rates as a function of time of treatment in relation to poisoning have not been performed. Two experiments are reported here. In the first the survival of lethally poisoned rats was compared after intravenously injecting either SUP prepared from cultured hepatocytes of syngeneic adult or fetal rat sources, or CYT-H from syngeneic adult rats 20 hr after poisoning. Untreated rats, rats treated with culture media alone, or rats treated with CYT from a nonregenerating source had an 88-100% mortality, with all deaths occurring within 72 hr following poisoning. Improved survival followed all other treatments: 55% of the rats receiving adult SUP, 70% of the rats receiving fetal SUP, and 80% of the rats receiving CYT-H survived. In the second experiment the survival of poisoned rats was compared after injecting them with PHP-neu, PHP not treated with neuraminidase (PHP without neu), and neuraminidase-treated plasma from sham-operated rats (SP-neu) or normal, nonoperated rats (NP-neu) 20 hr after poisoning.(ABSTRACT TRUNCATED AT 250 WORDS)