Gliotoxin non-selectively induces apoptosis in fibrotic and normal livers
Article first published online: 16 DEC 2005
Volume 26, Issue 2, pages 232–239, March 2006
How to Cite
Hagens, W. I., Olinga, P., Meijer, D. K. F., Groothuis, G. M. M., Beljaars, L. and Poelstra, K. (2006), Gliotoxin non-selectively induces apoptosis in fibrotic and normal livers. Liver International, 26: 232–239. doi: 10.1111/j.1478-3231.2005.01212.x
- Issue published online: 31 JAN 2006
- Article first published online: 16 DEC 2005
- Received 11 July 2005, accepted 3 October 2005
- precision-cut liver slices
Abstract: Background: Liver fibrosis is the common response to chronic liver injury, ultimately leading to cirrhosis. Several lines of evidence indicate that inducing apoptosis of hepatic stellate cells (HSC) may lead to regression of liver fibrosis. Recently, it was shown that gliotoxin (GTX) induces apoptosis of HSC. However, the clinical use of GTX may be limited because of the lack of cell and tissue specificity, causing a high risk of potentially severe adverse effects. The aim of this study, therefore, was to study the effect of GTX on different cells of the liver.
Methods: We used normal and fibrotic precision-cut rat liver slices to study the effect of GTX on the various resident liver cell types. In these slices, the complex cell–cell interactions are preserved, which closely mimics the in vivo situation.
Results: GTX exhibited a potent apoptosis-inducing activity in these slices. Both immunohistochemical stainings and real-time mRNA techniques showed that this apoptosis-inducing effect was seen in HSC. However, Kupffer cells and liver endothelial cells were also affected by GTX, whereas hepatocytes were only mildly affected.
Conclusions: This study indicates that the apoptosis-inducing strategy to treat liver fibrosis has high potential, but it will be necessary to develop an HSC-specific therapy to prevent adverse effects.