Dynamics of Collagen Accumulation and Activity of Collagen-Degrading Enzymes in the Liver of Rats with Carbon Tetrachloride-Induced Hepatic Fibrosis

Abstract

Liver fibrosis in rats was induced by repeated subcutaneous injections of carbon tetrachloride. Total collagen, soluble and insoluble collagen fractions as well as type I and type III collagen content in the liver were subsequently measured over a 3-18 week period. Liver collagen was found to increase exponentially during this time. Insoluble collagen accumulated more rapidly than soluble forms, and the accumulation of type III collagen was relatively greater than type I collagen. Changes in specific liver enzymes were also observed. Collagenase, collagenolytic cathepsin and collagen peptidase activities all increased. Levels of collagen-degrading enzymes increased rapidly during the first weeks of fibrosis-induction, and were followed by a more gradual increase during the remainder of the study.

Reduced collagenolytic activity of matrix metalloproteinases and development of liver fibrosis in the aging rat

“…The same pattern is also described in CCl 4 -treated rats (Kucharz, 1987). Accordingly, the separate analysis of the two major interstitial COL proteins showed a prevalent increase of type III over the type I collagen in our study.…”

Three-dimensional organization of the collagen fibrillar framework of the human and rat livers.

“…Both Type I and III collagens have been demonstrated immunohistochemically in normal and fibrotic liver (REMBERGER et al, 1975;GAY et al, of Human and Rat Livers 483 1975;NOWACK et al, 1976;ROJKIND et al, 1979;Voss et al, 1980;KONOMI et al, 1981;CLEMENT et al, 1984;BEDOSSA et al, 1987;KUCHARZ, 1987). Some researchers (SEVER, HUTCHESON and KANG, 1977;HAHN et al, 1980;Voss et al, 1980;RAUTERBERG et al, 1981) have reported very similar distributions of Types I and III collagens within the lobuli of the normal liver.…”

“…Recent immunohistochemical techniques have visualized type I, III and IV collagen in both normal and fibrotic livers (REMBERGER et al, 1975;GAY et al, 1975;NoWACK et al, 1976;ROJKIND et al, 1979;VOSS et al, 1980;KONOMI et al, 1981;CLEMENT et al, 1984;BEDOSSA et al, 1987;KUCHARZ, 1987). However, as these authors used light microscopes with limited resolving power, the detailed arrangement of the collagen fibrils in their natural locations and shapes remained to be studied.…”

Effect of Dietary Avocado Oils on Hepatic Collagen Metabolism

“…Although hepatic collagen content was not altered, the accu mulation of collagen clusters near the lipid droplet location in the fatty liver ( fig. 3) sup ports the possibility of early stages of focal fibrosis formation in the rats fed URAO [9], Hepatic collagen deposition during fat infil tration. caused by CC14 intoxication [22] or by ethanol administration [23], is a well-doc umented finding.…”

“…6] and Lamaud et al [7] showed that feeding or topical applica tion of unsaponifiable material obtained from avocado and soybean lipidic extracts caused an increase in collagen solubility in rat's skin. Collagen is the major structural protein component in vertebrates and in normal mammalian liver it accounts for about 1 % of the total dry weight [8], Exten sive deposition of collagen, as produced by various hepatotoxins, is a prominent feature of liver injury [9], This component of the hepatic extracellular biomatrix has received increasing interest due to its role in the pathogenesis of liver cirrhosis [10] in which fibrosis is generalized and is responsible for distorting normal histoarchitecture. A fibrotic response may be induced by any nox ious agent of a physical (temperature, radia tion, incision), chemical (CCU, bleomycin) or biological (infection, immune reaction) nature [11].…”