Document Detail


Troxerutin protects the isolated perfused rat liver from a possible lipid peroxidation by coumarin.
MedLine Citation:
PMID:  15693708     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
For more than 40 years coumarin has been successfully used in the therapy of chronic venous insufficiency (CVI). The occurrence of liver injuries is rather rare and happens predominantly when doses are administered which are significantly higher than necessary for therapeutical use. Such effects caused by high coumarin concentrations are reproducible in in vivo experiments in mice or rats and HepG2-cells. In order to characterize the mechanism of liver injuries, the isolated perfused rat liver has been chosen as model. Since liver injuries are quite rare, if coumarin is used in co-medication with troxerutin, a possible protective influence of this flavonoid has been investigated. In concentrations higher than 4 mmol/l, coumarin alone is effective in the isolated perfused rat liver. Then the release of the enzymes alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) increases and there is a measurable reduction of perfusion flow, oxygen consumption and rate of bile secretion. Additionally, the concentrations of hepatic adenosine triphosphate (ATP) and oxidized and total glutathione (GSSG/GSH) decrease. In the livers of fasting animals, coumarin doubles the concentration of hepatic malondialdehyde (MDA). This effect cannot be detected if troxerutin is added. In general, troxerutin reduces the concentration of all coumarin-metabolites in the perfusate and bile and changes the ratio of the main metabolites, coumarin: 3-hydroxycoumarin: 7-hydroxycoumarin. An analysis of the metabolic steps also shows that the amount of coumarin eliminated via faeces does not stem from absorbed coumarin, because the amount of orally applied coumarin detectable in the bile is less than 1%. The study demonstrates that troxerutin has hepatoprotective properties and thus protects the liver from a possible lipid peroxidation caused by coumarin. However, it is necessary to point out that these adverse effects caused by coumarin can be detected only in very high concentrations considerably above the regular therapeutical dosage. This allows the conclusion that troxerutin is a beneficial cofactor in coumarin preparations used for the therapy of chronic venous insufficiency.
Authors:
B S Adam; R Pentz; C P Siegers; O Strubelt; M Tegtmeier
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Phytomedicine : international journal of phytotherapy and phytopharmacology     Volume:  12     ISSN:  0944-7113     ISO Abbreviation:  Phytomedicine     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2005-02-07     Completed Date:  2005-04-13     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9438794     Medline TA:  Phytomedicine     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  52-61     Citation Subset:  IM    
Affiliation:
Institute of Experimental and Clinical Pharmacology and Toxicology, Medical University of Luebeck, D-23538 Lübeck, Germany.
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MeSH Terms
Descriptor/Qualifier:
Alanine Transaminase / blood
Animals
Anticoagulants / adverse effects*
Bile / secretion
Coumarins / adverse effects*
Drug-Induced Liver Injury / enzymology,  etiology,  prevention & control*
Glutamate Dehydrogenase / blood
Hydroxyethylrutoside / administration & dosage,  analogs & derivatives*,  pharmacology*,  therapeutic use
L-Lactate Dehydrogenase / blood
Lipid Peroxidation
Male
Melilotus*
Phytotherapy*
Plant Extracts / administration & dosage,  pharmacology,  therapeutic use
Protective Agents / administration & dosage,  pharmacology*,  therapeutic use
Rats
Rats, Wistar
Chemical
Reg. No./Substance:
0/Anticoagulants; 0/Coumarins; 0/Hydroxyethylrutoside; 0/Plant Extracts; 0/Protective Agents; 7085-55-4/troxerutin; 91-64-5/coumarin; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 1.4.1.2/Glutamate Dehydrogenase; EC 2.6.1.2/Alanine Transaminase

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