| Cyclosporine A-induced acute hepatotoxicity in guinea pigs is associated with endothelin-mediated decrease in local hepatic blood flow. | |
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MedLine Citation:
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PMID: 21356218 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Aims To bring further insight into the mechanism of cyclosporine A (CsA)-induced hepatotoxicity, the acute effect of CsA on local hepatic blood flow (LHBF) and its association with systemic hemodynamics, histopathological and biochemical indicators of liver toxicity were studied in guinea pigs in vivo. The association of endothelin (ET) and/or Cremophore-EL (C-EL, vehicle in parenteral CsA preparation) with CsA effects was also investigated. Main methods Animals were assigned into five groups; control, CsA, C-EL, Bosentan (non-selective ET receptor antagonist)+CsA, and BQ-123 (ET(A) receptor antagonist)+CsA. CsA was infused intravenously (i.v.) at 20 and 10mg/kg doses by 15min interval. Antagonists were administered 15min before CsA infusion. LHBF and mean arterial blood pressure (MAP) changes were simultaneously recorded. Blood and liver samples were collected for biochemical and histopathological examinations. Key findings CsA, but not C-EL, decreased LHBF by 53.3% at the end of 30min. Although being non-significant, CsA slightly increased MAP suggesting that, CsA-induced acute decrease in LHBF was likely independent of MAP changes. Bosentan (5mg/kg, i.v.) and BQ-123 (1mg/kg, i.v.) pre-treatments prevented the CsA-induced decrease in LHBF suggesting that CsA decreases LHBF through an ET-related mechanism. Additionally, CsA, but not its vehicle C-EL, caused marked acute pathological changes in the liver morphology. Significance CsA-induced findings of acute hepatotoxicity were prevented by bosentan and BQ-123 pre-treatments. Thus, CsA seems to exert acute hepatotoxic effect through ET-related mechanisms. |
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Authors:
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S Remzi Erdem; Selda Emre-Aydıngöz; Pergin Atilla; A Nur Cakar; Turgay Dalkara; Hayrunnisa Bolay; Meral Tuncer |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-2-25 |
Journal Detail:
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Title: Life sciences Volume: - ISSN: 1879-0631 ISO Abbreviation: - Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-3-1 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375521 Medline TA: Life Sci Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2010. Published by Elsevier Inc. |
Affiliation:
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Başkent University, Faculty of Medicine, Department of Pharmacology. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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