Abstract | BACKGROUND AND AIMS: METHODS: RESULTS: Histopathological examination revealed significant arrest of progression to cirrhosis in group 1 and reversal of cirrhosis in group 2 rats. TAK-044 treatment caused significant amelioration of portal hypertension, systemic hypotension, and liver injury (reduced activities of serum aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase), and improved hepatic synthetic capacity (increased serum albumin concentration) in both groups of rats relative to vehicle treated rats. TAK-044 treatment reduced collagen synthesis, as evidenced by decreased hepatic hydroxyproline content, mRNA expression of collagen-alpha type I, and tissue inhibitors of matrix metalloproteinases 1 and 2, and mRNA and protein expression of a potent fibrogenic cytokine, transforming growth factor beta1. CONCLUSIONS: The results emphasise the role of ET-1 in the development of cirrhosis and strongly suggest that blockade of its actions can be a rational therapy for chronic liver disease and its complications.
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Authors | C Thirunavukkarasu, Y Yang, V M Subbotin, S A K Harvey, J Fung, C R Gandhi |
Journal | Gut
(Gut)
Vol. 53
Issue 7
Pg. 1010-9
(Jul 2004)
ISSN: 0017-5749 [Print] England |
PMID | 15194653
(Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Endothelin Receptor Antagonists
- Endothelin-1
- Peptides, Cyclic
- Receptors, Endothelin
- TAK 044
- Carbon Tetrachloride
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Topics |
- Animals
- Carbon Tetrachloride
- Disease Progression
- Endothelin Receptor Antagonists
- Endothelin-1
(metabolism, physiology)
- Hypertension, Portal
(drug therapy)
- Liver
(metabolism)
- Liver Cirrhosis, Experimental
(chemically induced, drug therapy, metabolism, pathology)
- Male
- Peptides, Cyclic
(therapeutic use)
- Rats
- Rats, Sprague-Dawley
- Receptors, Endothelin
(metabolism)
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