The Integrated Value of Serum Procollagen Iii Peptide Over Time Predicts Hepatic Hydroxyproline Content and Stainable Collagen in A Model of Dietary Cirrhosis in the Rat

Abstract

To determine whether a serum parameter of collagen metabolism, serum procollagen type III peptide, correlated with hepatic collagen in a model of diet-induced fibrosis, rats were fed a control or cirrhogenic diet for 6 months and treated with either subcutaneous vehicle or the hepatoprotective prostaglandin 16,16-dimethyl prostaglandin E2 (100 micrograms per kg) twice daily. Pair-fed rats from each group were killed after 2, 4 or 6 months. The value of serum procollagen type III peptide to body weight integrated over time (Kt) correlated linearly with hepatic hydroxyproline content (r = 0.97) at killing time t. Good correlations were also seen between Kt and histopathological assessment of aniline blue-stainable collagen (r = 0.93) and between the histopathology and hydroxyproline content (r = 0.97). Rats receiving 16,16-dimethyl prostaglandin E2 had lower values of all three parameters compared to rats receiving vehicle, confirming the previously demonstrated hepatoprotective effect of 16,16-dimethyl prostaglandin E2. The excellent correlation between Kt and the two other traditional parameters of hepatic collagen suggest that sequential measurements of serum procollagen type III peptide can be used to predict alterations in liver collagen deposition in rats.

Selective inhibition of hepatic collagen accumulation in experimental liver fibrosis in rats by a new prolyl 4-hydroxylase inhibitor

“…Our findings with malotilate are in agreement with the results of other investigators after short-and long-term treatment with CCl 4 , [23][24][25][26] interpreting the effects of malotilate on collagen biosynthesis in CCl 4 -induced liver fibrosis as caused by the reduction of postnecrotic inflammation. 26 It has been shown 27,28 that serum collagen fragments, especially PIIINP, are predictive markers in different models of experimental liver fibrosis in rodents. The present data show for the first time that PIIINP was closely correlated (r ϭ .706; P Ͼ .001) to Hyp in the liver under the influence of a P4H inhibitor, suggesting that the efficacy of such compounds can be monitored by a surrogate variable like PIIINP in serum.…”

<i>Antrodia cinnamomea</i> extract attenuates carbon tetrachloride-induced chronic liver fibrosis in Sprague-Dawley rats

“…The degree of liver injury was assessed according to the criteria described in Knodell et al (1981), whereas the semi-quantitative analysis of liver fibrosis was assessed as described in Ruwart et al (1989). The sections were evaluated blindly by a veterinary pathologist (LCW).…”

Fibro-C-Index: comprehensive, morphology-based quantification of liver fibrosis using second harmonic generation and two-photon microscopy

“…Animal tissue scoring was performed using a modified Ruwart score according to Boigk et al, as there was extensive bile duct proliferation noted, 36,38 making the modified Ishak score unsuitable. 8 Human samples were scored according to the modified Ishak score.…”

“…36,37 We have established a comprehensive animal model with different stages of liver fibrosis for both the qualitative and quantitative measurements of collagen content in fibrotic livers. Using the SHG system, we recorded 3-D collagen progression patterns in high spatial resolution.…”