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Original Article
November 1, 2006

Therapeutic Potential of Cardiotrophin 1 in Fulminant Hepatic Failure: Dual Roles in Antiapoptosis and Cell Repair

Author Affiliations

Author Affiliations: Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong.

Arch Surg. 2006;141(11):1077-1084. doi:10.1001/archsurg.141.11.1077

Hypothesis  Administration of cardiotrophin 1 (CT-1) can treat experimental fulminant hepatic failure (FHF).

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

Setting  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.

Animals  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.

Conclusion  Cardiotrophin 1 may improve the outcome of D-gal–induced FHF through its effects on antiapoptosis and cell repair.