Therapeutic potential of cardiotrophin 1 in fulminant hepatic failure: dual roles in antiapoptosis and cell repair.
OBJECTIVE
Administration of cardiotrophin 1 (CT-1) can treat experimental fulminant hepatic failure (FHF).


METHODS
Rat model with FHF induced by D-galactosamine (D-gal).


METHODS
Fulminant hepatic failure is a rapidly progressive disease that lacks effective nonsurgical treatment. Cardiotrophin 1 is a member of the interleukin 6 family that can protect cells from damage in some animal disease models.


METHODS
A rat model of FHF was induced by an intraperitoneal injection of D-gal (1.4 g/kg of body weight). Cardiotrophin 1 was administered at different time points after D-gal injection.


RESULTS
Administration of CT-1 at 12 and 18 hours had a survival rate of 80% (12/15) and 70% (7/10), respectively, which was significantly higher than that of nontreatment (28% [5/18]). In addition, improvement of liver histologic findings, shortening of activated clotting time, and decrease in serum levels of total bilirubin and alanine aminotransferase were detected with CT-1 treatment. Administration of CT-1 decreased apoptotic cells and increased Ki-67 cells in the liver tissues. In vitro, CT-1 administration significantly decreased apoptotic cells and sequentially down-regulated the expression of proapoptotic molecules and up-regulated the expression of antiapoptotic molecules at different culture periods. D-galactosamine culture induced morphologic damage in a hepatocyte cell line, which was greatly improved by CT-1 administration. In addition, CT-1-treated cells demonstrated increased expression of glycoprotein 130 and up-regulation of cyclin D1 and heat shock protein 90.


CONCLUSIONS
Cardiotrophin 1 may improve the outcome of D-gal-induced FHF through its effects on antiapoptosis and cell repair.
Ho
David W
DW
Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong.
Yang
Zhen Fan
ZF
Lau
Chi Keung
CK
Tam
Ka Ho
KH
To
Jensen Y
JY
Poon
Ronnie T
RT
Fan
Sheung Tat
ST
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005696:Galactosidases; D022781:Hepatocytes / Q000187:drug effects*; D017114:Liver Failure, Acute / Q000188:drug therapy* / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D051381:Rats; D015996:Survival Rate
D016207:Cytokines; C092073:cardiotrophin 1; D005696:Galactosidases