elastin and Carbon-Tetrachloride-Poisoning

Elastin is an amorphous protein highly resistant to elastase degradation and is believed to be the most stable component among the extracellular matrix (ECM) members. Thus the excessive deposition of elastin in advanced liver fibrosis may contribute to the declining reversibility of the disease. Our previous study has found that elastin crosslinking inhibition can effectively arrest liver fibrosis progression. To further understand the roles of elastin involved in liver fibrosis, we systematically investigated the expression, accumulation, and degradation based on dynamic and bidirectional CCl

Topics: Animals; Carbon Tetrachloride Poisoning; Collagen; Elastin; Gene Expression Regulation; Hepatocytes; Humans; Imaging, Three-Dimensional; Liver Cirrhosis; Mice; Tropoelastin

Isolation and structure analysis of two amino acids from bovine ligamentum nuchae elastin hydrolysates revealed the presence of pyridine cross-links in elastin. The structures of these amino acids were determined to have 3,4,5- and 2,3,5-trisubstituted pyridine skeletons both with three carboxylic acids and a mass of 396 (C(18)H(28)N(4)0(6)) identified as 4-(4-amino-4-carboxybutyl)-3,5-di-(3-amino-3-carboxypropyl)-pyridine and 2-(4-amino-4-carboxybutyl)-3,5-di-(3-amino-3-carboxypropyl)-pyridine. We have named these pyridine cross-links desmopyridine (DESP) and isodesmopyridine (IDP), respectively. Structure analysis of these pyridine cross-links implied that the formation of these cross-links involved the condensation reaction between ammonia and allysine. The elastin incubated with ammonium chloride showed that DESP and IDP levels increased as the allysine content decreased. DESP and IDP were measured by high pressure liquid chromatography (HPLC) with UV detection and were found in a variety of bovine tissues. The DESP/desmosine (DES) and IDP/isodesmosine (IDE) ratios in aorta elastin were higher than in other tissues. DESP and IDP contents in human aorta elastin were found to be gradually increased with age. The concentration of IDP was significantly elevated in aorta elastin of rat with chronic liver cirrhosis induced by carbon tetrachloride (mean +/- S.D.; 11.1 +/- 0.9 nmol/mg elastin) when compared with normal rats (5.9 +/- 1.5 nmol/mg elastin). Although DESP and IDP are present at only trace concentrations in the tissue elastin, these pyridine cross-links may be useful biomarkers for the aortic elastin damaged by ammonia.

Topics: 2-Aminoadipic Acid; Aging; Amino Acids; Ammonium Chloride; Animals; Aorta; Carbon Tetrachloride Poisoning; Cattle; Chromatography, High Pressure Liquid; Cross-Linking Reagents; Elastin; Humans; Liver; Liver Cirrhosis, Experimental; Lung; Male; Nuclear Magnetic Resonance, Biomolecular; Pyridines; Rats; Rats, Wistar; Reference Values

Hepatic fibrosis was induced in rats by poisoning them with carbon tetrachloride. The influence of anti-inflammatory steroids (hydrocortisone, prednisone, dexamathasone) upon elastin content in liver was investigated in healthy and CCl4 intoxicated rats. An increase of liver elastin content was observed in animals with CCl4-induced hepatic fibrosis Opposite results were obtained in normal rats after treating them with glucocorticosteroids. A decrease of elastin content after steroid treatment was also found in rats with injured liver, as compared to animals receiving CCl4 only. Presumable mechanisms of the results are discussed.

Topics: Animals; Anti-Inflammatory Agents; Carbon Tetrachloride Poisoning; Elastin; Glucocorticoids; Liver; Liver Cirrhosis; Male; Rats; Rats, Inbred Strains

Elastin fibers formation was previously found to be an important feature of advanced human liver cirrhosis. Now it has been shown that chronic carbon tetrachloride administration to rats can be used to simulate this condition experimentally. Elastin fibers are found in the septa of connective tissue surrounding parenchymal nodules. Elastin content in liver measured as hydroxyproline insoluble in 0.1 N NaOH is increased about 3 times after a 4 month carbon tetrachloride treatment.

Topics: Animals; Carbon Tetrachloride Poisoning; Connective Tissue; Elastin; Hydroxyproline; Liver; Liver Cirrhosis; Male; Rats

Attempt has been made to study histochemically the disposition of connective tissue fibrils in the liver of common ground squirrel, Funambulus pennanti in cirrhotic and necrotic conditions caused by carbon tetrachloride treatment. Evidence has been put forward to show that no reticulin remains in the liver during these conditions. However the percentage of elastin and collagen increases with a change in arrangement. Probable causes of this topographical change in localization are discussed comparing the results with controls.

Topics: Animals; Carbon Tetrachloride Poisoning; Collagen; Connective Tissue; Connective Tissue Cells; Elastin; Histocytochemistry; Reticulin; Sciuridae