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Ribavirin inhibits angiogenesis by tetrahydrobiopterin depletion.

Michaelis, Martin, Michaelis, U. Ruth, Suhan, Tatyana, Schmidt, Helmut, Mohamed, Annisuddin, Doerr, Hans Wilhelm, Cinatl, Jindrich (2007) Ribavirin inhibits angiogenesis by tetrahydrobiopterin depletion. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 21 (1). pp. 81-7. ISSN 1530-6860. (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)

Abstract

Ribavirin is a broad-spectrum antiviral drug that is used to treat hepatitis C virus (HCV)-infected patients. The virological response after ribavirin treatment appears to be insufficient to fully explain ribavirin-induced beneficial effects. Angiogenesis plays a pathogenic role in HCV-induced liver damage. Here, we investigated the influence of therapeutic ribavirin concentrations on angiogenesis. Ribavirin inhibited endothelial cell tube formation in vitro and vessel formation in the chick chorioallantoic membrane assay in vivo. Ribavirin inhibits inosine monophosphate dehydrogenase, which causes depletion of cellular GTP and in turn reduction of cellular tetrahydrobiopterin levels. The availability of tetrahydrobiopterin limits NO production by endothelial NO synthase. Ribavirin reduced levels of tetrahydrobiopterin (as revealed by HPLC), NO (as revealed by electron spin resonance spectroscopy), and cGMP (as revealed by RIA) in endothelial cells. Addition of tetrahydrobiopterin or NO prevented ribavirin-induced tube formation inhibition. In conclusion, angiogenesis inhibition by ribavirin has not been described before. This inhibition may contribute to ribavirin-induced pharmacological effects including adverse events.

Item Type: Article
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Martin Michaelis
Date Deposited: 05 Jun 2013 20:59 UTC
Last Modified: 29 May 2019 10:14 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/34096 (The current URI for this page, for reference purposes)
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