The Fas/Fas-ligand system functions in hepatocytes in the early stage of fulminant hepatic failure in rats

Apoptosis is involved in various liver diseases, but in the case of fulminant hepatic failure (FHF) much remains to be determined. We investigated apoptosis in the remnant liver lobes of FHF rats regarding the Fas/Fas ligand and the TGF-beta system. Rats (n = 30) with FHF were euthanized at postoperative 3, 6, 12, 24 and 36 h. Changes in the Fas/Fas-ligand and TGF-beta were studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical staining. Apoptosis was explored using terminal deoxynucleotidyl transferase mediated dUDP-nick end labeling method (TUNEL). Within 6 h, a relatively large number of hepatocytes, mainly in zone 3, were apoptotic. During the same period, the expression of Fas and Fas-ligand mRNA and protein, but not that of TGF-beta, were observed and decreased with time. Both Fas and Fas-ligand proteins were present in the hepatocytes in zone 3. These results suggest that the Fas/Fas-ligand system, rather than TGF-beta, has a role in apoptosis during the early stages of FHF, possibly through an autocrine loop. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.