Abstract | BACKGROUND & AIMS: METHODS: Measurements were performed that included: mean arterial pressure, cardiac index (CI), systemic vascular resistance, superior mesenteric arterial blood flow and resistance, PVP, plasma endotoxin and hepatic tumor necrosis factor-α (TNFα), anandamide and 2-arachidonylglycerol, hepatic expression of cannabinoid receptors, endothelial nitric oxide synthase (eNOS), phospho-eNOS, Akt, phospho-Akt and thromboxane synthase (TXS), matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2), hepatic fibrosis, and leukocyte infiltration. Hepatic endothelial dysfunction was evaluated in BDL rats receiving vehicle (BDL-V) or 2-weeks of ciprofloxacin (BDL- cipro). RESULTS: Plasma endotoxin and hepatic TNFα, anandamide and 2-arachidonylglycerol, expression of TXS, MMP-2, TIMP-2, hepatic fibrosis and infiltration of hepatic leukocytes, CI, PVP and intrahepatic resistance were significantly lower in BDL- cipro than in BDL-V rats. Conversely, systemic vascular resistance, eNOS and Akt phosphorylation were significantly higher in BDL- cipro than in BDL-V rats. Improvement of hepatic endothelial dysfunction was associated with lower expression of hepatic CB(1) and a higher expression of hepatic CB(2) in BDL- cipro rats. CONCLUSIONS: In cirrhotic rats, ciprofloxacin suppressed endotoxemia and the hepatic endocannabinoid system thus ameliorating hyperdynamic circulation and decreased intrahepatic resistance by preventing hepatic fibrogenesis and endothelial dysfunction.
|
Authors | Han-Chieh Lin, Ying-Ying Yang, Tung-Hu Tsai, Chih-Ming Huang, Yi-Tsau Huang, Fa-Yauh Lee, Tze-Tze Liu, Shou-Dong Lee |
Journal | Journal of hepatology
(J Hepatol)
Vol. 54
Issue 6
Pg. 1145-53
(Jun 2011)
ISSN: 1600-0641 [Electronic] Netherlands |
PMID | 21145843
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. |
Chemical References |
- Anti-Bacterial Agents
- Cannabinoid Receptor Modulators
- Endocannabinoids
- RNA, Messenger
- Receptor, Cannabinoid, CB1
- Receptor, Cannabinoid, CB2
- Ciprofloxacin
|
Topics |
- Animals
- Anti-Bacterial Agents
(therapeutic use)
- Cannabinoid Receptor Modulators
(metabolism)
- Ciprofloxacin
(therapeutic use)
- Disease Models, Animal
- Endocannabinoids
- Endotoxemia
(complications, drug therapy, metabolism, physiopathology)
- Hypertension, Portal
(complications, metabolism, physiopathology)
- Liver
(metabolism, pathology)
- Liver Circulation
(drug effects)
- Liver Cirrhosis
(complications, metabolism, pathology, physiopathology)
- Male
- RNA, Messenger
(genetics, metabolism)
- Rats
- Rats, Sprague-Dawley
- Receptor, Cannabinoid, CB1
(genetics, metabolism)
- Receptor, Cannabinoid, CB2
(genetics, metabolism)
|
|
Join CureHunter, for free Research Interface BASIC access!
Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease.
Find out why thousands of doctors, pharma researchers and patient activists
around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!
|