Therapeutic potential of cardiotrophin 1 in fulminant hepatic failure: dual roles in antiapoptosis and cell repair

Arch Surg. 2006 Nov;141(11):1077-84; discussion 1084. doi: 10.1001/archsurg.141.11.1077.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Apoptosis / drug effects*
  • Blotting, Western
  • Cell Line
  • Cytokines / pharmacology*
  • Disease Models, Animal
  • Flow Cytometry
  • Galactosidases
  • Hepatocytes / drug effects*
  • Liver Failure, Acute / drug therapy*
  • Liver Failure, Acute / pathology
  • Liver Function Tests
  • Male
  • Rats
  • Survival Rate

Substances

  • Cytokines
  • cardiotrophin 1
  • Galactosidases