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09:27
The Dimethylnitrosamine Induced Liver Fibrosis Model in the Rat
Published on: June 17, 2016
Cirrhosis and endotoxin decrease urea synthesis in rats.
Susanne Schouw Nielsen1, Thorbjørn Grøfte, Niels Tygstrup
1Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, Aarhus, Denmark.
Summary
Endotoxemia significantly impairs urea synthesis in cirrhotic rats, highlighting a key mechanism for increased infection mortality in human cirrhosis. This study reveals how endotoxins affect liver urea cycle function.
Area of Science:
- Hepatology
- Toxicology
- Molecular Biology
Background:
- Cirrhosis frequently leads to endotoxemia.
- Endotoxemia increases infection-related mortality in cirrhosis patients.
- The impact of endotoxins on urea synthesis and urea cycle genes in cirrhosis is not well understood.
Purpose of the Study:
- To investigate the effects of endotoxemia on urea synthesis and urea cycle gene expression in rats with experimental cirrhosis.
- To determine the role of endotoxins in the impaired metabolic function associated with cirrhosis.
Main Methods:
- Rats with bile duct ligation-induced cirrhosis and control rats were administered lipopolysaccharide (LPS).
- Measurements included urea nitrogen synthesis rate (UNSR), capacity of urea nitrogen synthesis (CUNS), liver mRNA levels of urea cycle enzymes (CPS, ASS), and galactose elimination capacity (GEC).
Main Results:
- Lipopolysaccharide (LPS) and cirrhosis with LPS administration significantly reduced UNSR by 40%.
- Cirrhosis combined with LPS administration decreased CUNS by 40%.
- Both cirrhosis and LPS decreased mRNA levels for carbamoyl phosphate synthetase (CPS) and arginine succinate synthetase (ASS); however, cirrhosis + LPS only affected ASS mRNA levels.
Conclusions:
- Endotoxemia severely impairs urea synthesis in experimental cirrhosis.
- This impaired urea synthesis may represent a critical pathophysiological mechanism contributing to the poor outcomes of endotoxemia in human cirrhosis.
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