Document Detail


Lipoic acid prevents development of the hyperdynamic circulation in anesthetized rats with biliary cirrhosis.
MedLine Citation:
PMID:  10216116     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chronic bile duct ligation is associated with the development of oxidant injury, biliary cirrhosis, portal hypertension, and a hyperdynamic circulation. We have previously demonstrated that the hyperdynamic circulation in the partial portal vein-ligated rat can be prevented by the administration of N-acetylcysteine. To extend these findings, we have examined the effect of lipoic acid, a thiol-containing antioxidant, on hemodynamics, oxidative stress, and nitric oxide (NO) production in bile duct-ligated (BDL) cirrhotic rats. Lipoic acid was given continuously in drinking water to normal and BDL rats; control rats received ordinary drinking water, and animals were studied at 24 days following surgery. Lipoic acid prevented the development of the hyperdynamic circulation (cardiac index [CI]: 15.7 +/- 2.0 vs. 29.5 +/- 2.1 mL x min-1 x 100 g-1; P <. 05) and significantly attenuated the rise in portal pressure (PP) (12.7 +/- 0.8 vs. 15.2 +/- 0.5 mm Hg; P <.05). Hepatic nitric oxide synthase (NOS) activity and plasma nitrite/nitrate concentration increased significantly following bile duct ligation, and both of these were prevented by lipoic acid. Lipoic acid had no effect on the biochemical or histological parameters of liver function in the cirrhotic group. We conclude that lipoic acid prevents the development of the hyperdynamic circulation in the rat model of biliary cirrhosis, and that this is associated with decreased synthesis of NO.
Authors:
R Marley; S Holt; B Fernando; D Harry; R Anand; D Goodier; S Davies; K Moore
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  29     ISSN:  0270-9139     ISO Abbreviation:  Hepatology     Publication Date:  1999 May 
Date Detail:
Created Date:  1999-05-19     Completed Date:  1999-05-19     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1358-63     Citation Subset:  IM    
Affiliation:
Department of Medicine, The Royal Free and University College Medical School, London, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Circulation / drug effects*
Cardiovascular Diseases / prevention & control*
Glutathione / metabolism
Hemodynamics / drug effects
Lipid Peroxides / blood
Liver / enzymology,  metabolism,  pathology
Liver Cirrhosis, Biliary / drug therapy*,  metabolism,  pathology,  physiopathology
Male
Nitrates / blood
Nitric Oxide Synthase / metabolism
Nitrites / blood
Rats
Rats, Sprague-Dawley
Reference Values
Thioctic Acid / therapeutic use*
Chemical
Reg. No./Substance:
0/Lipid Peroxides; 0/Nitrates; 0/Nitrites; 62-46-4/Thioctic Acid; 70-18-8/Glutathione; EC 1.14.13.39/Nitric Oxide Synthase

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