The aim of the study was to examine whether a rat model of liver cirrhosis induced by carbon tetrachloride (CCl4) is a suitable model of muscle wasting and alterations in amino acid metabolism in cirrhotic humans. Rats were treated by intragastric gavage of CCl4 or vehicle for 45 days. Blood plasma and different muscle types-tibialis anterior (mostly white fibres), soleus (red muscle) and extensor digitorum longus (white muscle) - were analysed at the end of the study. Characteristic biomarkers of impaired hepatic function were found in the plasma of cirrhotic animals. The weights and protein contents of all muscles of CCl4-treated animals were lower when compared with controls. Increased concentrations of glutamine (GLN) and aromatic amino acids (phenylalanine and tyrosine) and decreased concentrations of branched-chain amino acids (BCAA), glutamate (GLU), alanine and aspartate were found in plasma and muscles. In the soleus muscle, GLN increased more and GLU and BCAA decreased less than in the extensor digitorum and tibialis muscles. Increased chymotrypsin-like activity (indicating enhanced proteolysis) and decreased α-ketoglutarate and ATP levels were found in muscles of cirrhotic animals. ATP concentration also decreased in blood plasma. It is concluded that a rat model of CCl4-induced cirrhosis is a valid model for the investigation of hepatic cachexia that exhibits alterations in line with a theory of role of ammonia in pathogenesis of BCAA depletion, citric cycle and mitochondria dysfunction, and muscle wasting in cirrhotic subjects. The findings indicate more effective ammonia detoxification to GLN in red than in white muscles.
- MeSH
- adenosintrifosfát nedostatek MeSH
- chlorid uhličitý farmakologie MeSH
- jaterní cirhóza chemicky indukované komplikace metabolismus patologie MeSH
- kosterní svaly metabolismus patologie MeSH
- kyseliny ketoglutarové metabolismus MeSH
- modely nemocí na zvířatech MeSH
- potkani Wistar MeSH
- přijímání potravy účinky léků MeSH
- sarkopenie etiologie metabolismus patologie MeSH
- svalové proteiny metabolismus MeSH
- tělesná hmotnost účinky léků MeSH
- velikost orgánu účinky léků MeSH
- větvené aminokyseliny metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- buňky pojivové tkáně chemie patologie MeSH
- chlorid uhličitý farmakologie MeSH
- cytoskeletální proteiny chemie MeSH
- experimentální cirhóza jater chemicky indukované patologie MeSH
- finanční podpora výzkumu jako téma MeSH
- imunohistochemie MeSH
- modely nemocí na zvířatech MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- buňky pojivové tkáně cytologie fyziologie patologie MeSH
- chlorid uhličitý farmakologie MeSH
- finanční podpora výzkumu jako téma MeSH
- jaterní cirhóza chemicky indukované MeSH
- krysa rodu rattus MeSH
- potkani Wistar MeSH
- RNA izolace a purifikace MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
