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.
- Klíčová slova
- ammonia detoxification, cachexia, glutamine, liver cirrhosis,
- 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
- Názvy látek
- adenosintrifosfát MeSH
- chlorid uhličitý MeSH
- kyseliny ketoglutarové MeSH
- svalové proteiny MeSH
- větvené aminokyseliny MeSH
A combination of treating outdated packed red blood cells (PRBCs) with carbontetrachloride, countercurrent dialysis and modified conditions of freeze-drying served to improve and standardize the technology of "stroma-free hemolysate" (SFH) in our laboratory. As a rule, proteins of the final product corresponded to 95% oxyhemoglobin, 3.5% methemoglobin and 1.5% non-hemoglobin ones. In freeze-dried samples stabilized with 0.24 molar saccharides, the weight proportions were 56% hemoglobin, 44% sucrose and/or 62% hemoglobin, and 38% fructose, respectively. If necessary, the saccharides could be rapidly removed from the easily reconstituted SFH by dialysis or chromatography. Analytical parameters were similar to those of chloroform-treated SFH stored dry at -12 degrees C for 4 months. However, the present procedure was easier and SFH samples remained unchanged after dry storage even at +4 degrees C for at least 13 months. This oxyhemoglobin product seems suitable for organ perfusion, further chemical modification and as an analytical standard.
- MeSH
- chlorid uhličitý farmakologie MeSH
- chloroform farmakologie MeSH
- erytrocyty účinky léků MeSH
- konzervace krve MeSH
- lidé MeSH
- lyofilizace * MeSH
- metody MeSH
- oxyhemoglobiny izolace a purifikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chlorid uhličitý MeSH
- chloroform MeSH
- oxyhemoglobiny MeSH
Female Wistar rats were pretreated with I ml of carbon tetrachloride/kg of body weight or with olive oil. All the rats were given this dose of CCl4 20 or 40 days later. Liver regeneration as evaluated by 3H-thymidine incorporation into liver DNA and by the number of mitotic hepatocytes was markedly impaired in CCl4-pretreated rats when compared with olive oil-pretreated controls. DNA labelling reached only 83 and 59% and mitotic index 35 and 58% of control values, respectively, at 20-day and 40-day time intervals. The variables characteristic of liver damage did not parallel the changes in cell division. About 20% of hepatocytes were necrotic both in the CCl4-pretreated and in the control rats. The activity of serum alanine aminotransferase was higher in the CCl4-pretreated rats. Only serum aspartate aminotransferase activities were somewhat lower when compared to controls. Similarly, serum aminotransferases were much less affected by the pretreatment than the markers of regeneration when two low doses of CCl4 (0.125 ml/kg) were given to rats 20 days apart. The activities of microsomal enzymes aniline hydroxylase and pethidine demethylase were equal in control and in experimental rats 20 days after CCl4 pretreatment which indicated that the effects of CCl4 were not mediated by an overall decrease in cytochrome P-450 enzymes. In summary, a single pretreatment of rats with CCl4 induced changes in liver that lasted for 40 days and impaired liver regeneration when another dose of CCl4 was applied.
- MeSH
- alanintransaminasa účinky léků MeSH
- aspartátaminotransferasy účinky léků MeSH
- buněčné dělení účinky léků MeSH
- chlorid uhličitý farmakologie MeSH
- inbrední kmeny potkanů MeSH
- játra účinky léků patologie MeSH
- krysa rodu Rattus MeSH
- nekróza MeSH
- regenerace jater účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- alanintransaminasa MeSH
- aspartátaminotransferasy MeSH
- chlorid uhličitý MeSH
- MeSH
- chlorid uhličitý farmakologie MeSH
- ethanol farmakologie MeSH
- inbrední kmeny potkanů MeSH
- játra účinky léků metabolismus účinky záření MeSH
- krysa rodu Rattus MeSH
- kyslík metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chlorid uhličitý MeSH
- ethanol MeSH
- kyslík MeSH
- MeSH
- azauridin farmakologie MeSH
- chlorid uhličitý farmakologie MeSH
- glykoproteiny biosyntéza MeSH
- granulom metabolismus patofyziologie MeSH
- hydroxyprolin metabolismus MeSH
- inbrední kmeny potkanů MeSH
- játra účinky léků metabolismus MeSH
- krysa rodu Rattus MeSH
- kyselina N-acetylneuraminová MeSH
- kyseliny sialové metabolismus MeSH
- kyseliny uronové metabolismus MeSH
- regenerace jater účinky léků MeSH
- zánět metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- azauridin MeSH
- chlorid uhličitý MeSH
- glykoproteiny MeSH
- hydroxyprolin MeSH
- kyselina N-acetylneuraminová MeSH
- kyseliny sialové MeSH
- kyseliny uronové MeSH
- MeSH
- časové faktory MeSH
- centrální nervový systém účinky léků MeSH
- chlorid uhličitý krev farmakologie MeSH
- chloroform krev farmakologie MeSH
- krysa rodu Rattus MeSH
- regresní analýza MeSH
- rozpouštědla farmakologie MeSH
- toluen krev farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chlorid uhličitý MeSH
- chloroform MeSH
- rozpouštědla MeSH
- toluen MeSH
- MeSH
- alanintransaminasa metabolismus MeSH
- aspartátaminotransferasy metabolismus MeSH
- chlorid uhličitý farmakologie MeSH
- chloroform farmakologie MeSH
- chlorované uhlovodíky farmakologie MeSH
- fenobarbital farmakologie MeSH
- inbrední kmeny potkanů MeSH
- játra enzymologie MeSH
- krysa rodu Rattus MeSH
- methylenchlorid farmakologie MeSH
- sorbitoldehydrogenasa metabolismus MeSH
- trichlorethany farmakologie MeSH
- trichlorethylen farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 1,1,1-trichloroethane MeSH Prohlížeč
- alanintransaminasa MeSH
- aspartátaminotransferasy MeSH
- chlorid uhličitý MeSH
- chloroform MeSH
- chlorované uhlovodíky MeSH
- fenobarbital MeSH
- methylenchlorid MeSH
- sorbitoldehydrogenasa MeSH
- trichlorethany MeSH
- trichlorethylen MeSH
The authors performed a comparative biochemical study of some enzymes of lysosomic origin (hyaluronidase, N-acetyl-beta-D-glucosaminidase, beta-glucosidase, beta-galatosidase and acid phosphatase), of the state of enzyme substrate system N-acetylneuraminic acid---aldolase of neuramic acid and of the activity of lactatedehydrogenase (soluble in cytosol and bound on mitochodria) in the liver, lungs and blood serum of rats at various regimens of the inhalation action of CCl4. On the basis of results obtained they determined the biological importance of the change of activity of enzymes differently localized in cells at the adaptation of an organisme to the noxious action of CCl4.
- MeSH
- aldolasa metabolismus MeSH
- chlorid uhličitý farmakologie MeSH
- cytoplazma enzymologie MeSH
- hydrolasy metabolismus MeSH
- játra enzymologie ultrastruktura MeSH
- krysa rodu Rattus MeSH
- L-laktátdehydrogenasa metabolismus MeSH
- lyzozomy enzymologie MeSH
- plíce enzymologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- aldolasa MeSH
- chlorid uhličitý MeSH
- hydrolasy MeSH
- L-laktátdehydrogenasa MeSH
The authors effected a comparative examination of morphologic and biochemical investigation of structural and enzymic reactions of the rat liver during different periods of permanent inhalation influence of carbon tetrachloride. Three stages of morphologico-biochemical parllels in the development of hepatotropic effect characterized by certain regularities in the enzymic desorganization of lysosyme, mitochondrias and cytasol by derangement of the exchange of biopolymers containing carbohydrate (of glycoproteids, glycosaminoglycans) and DNK-synthetizing function in liver in comparison with control animals were revealed. Mechanisms of the hepatotropic effect and hygienic importance of structural function changes of hepatocytes due to action of factors polluting the atmosphere are appreciated.
- MeSH
- chlorid uhličitý farmakologie MeSH
- játra cytologie účinky léků enzymologie MeSH
- krysa rodu Rattus MeSH
- látky znečišťující vzduch škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chlorid uhličitý MeSH
- látky znečišťující vzduch MeSH
- MeSH
- aminopeptidasy krev MeSH
- arginin krev MeSH
- chlorid uhličitý farmakologie MeSH
- ovce krev MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- aminopeptidasy MeSH
- arginin MeSH
- chlorid uhličitý MeSH
