Elevated serum aminoterminal procollagen type-III-peptide parallels collagen accumulation in rats with secondary biliary fibrosis

Gerling, Burkard; Becker, Michael; Waldschmidt, J.; Rehmann, Martina; Schuppan, Detlef

doi:10.1016/s0168-8278(96)80331-x

Cited by 39 publications

(30 citation statements)

References 26 publications

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“…In this study, we selected and compared two kinds of rat models for hepatic fibrosis. One is BDL/s model and other is DMNadministration model [3,8]. In our study, both could produce well established hepatic fibrosis with rare inflammation and hepatocyte necrosis, and they were considered to be useful models for hepatic fibrosis.…”

Section: Discussionmentioning

confidence: 93%

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Enzyme-Linked Immunosorbent Assay for Serum Procollagen Type III Peptide in Rats with Hepatic Fibrosis.

Cho

Lee

1998

The Journal of Veterinary Medical Science

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ABSTRACT. The process of hepatic fibrosis, and the changes in contents of hepatic hyproxyproline (HYP) and serum procollagen type III peptide (PIIINP) were examined in two rat models for hepatic fibrosis, i.e. bile duct ligation/scission (BDL/s)-and dimethylnitrosamine (DMN)-induced models. In addition, an expression of type III collagen mRNA in the liver of BDL/s model was also examined. In BDL/ s model, hepatic fibrosis started at 2 weeks after operation (WAO) and cirrhosis with prominent bile duct hyperplasia was detected at and after 5 WAO. Serum PIIINP content measured using a modified double armed inhibition enzyme-linked immunosorbent assay (ELISA) method proposed by us started to increase at 1 WAO and continued to increase thereafter. Hepatic HYP content measured colorimetrically started to increase at 3 WAO and it continued to increase until 7 WAO. An expression of type III collagen mRNA in the liver was enhanced at and after 2 WAO, especially at 4 and 5 WAO. In DMN model, marked hepatic fibrosis was detected at 1 week after the last DMN administration (WAA), and the degree of fibrosis was apparently reduced at 4 WAA. Serum PIIINP content prominently increased at 1 WAA and decreased at and after 3 WAA. Hepatic HYP content showed a marked increase at 1 WAA and decreased thereafter. The present results indicated that the sequences of hepatic fibrosis, hepatic HYP content and serum PIIINP content were well correlated with each other in both BDL/s and DMN models. In conclusion, ELISA system for the detection of serum PIIINP content is considered to be reliable method for assessment of cirrhotic liver, and the present two rat models for liver fibrosis/cirrhosis seems to be a good tool for researching antifibrotic agents. -KEY WORDS: enzyme-linked immunosorbent assay, hepatic fibrosis model, rat, serum procollagen type III peptide.J. Vet. Med. Sci. 60(11): 1213-1220, 1998 and hepatocyte necrosis. Namely, bile duct ligation/scission (BDL/s) is recommended as a useful method for producing progressive and reproducible biliary fibrosis in rats without prominent hepatocyte necrosis and severe inflammation [9,19]. In addition, treatment with dimethylnitrosamine (DMN) is also known to have an advantage to induce fibrosis in rats in a relatively short period (3 weeks) with slight inflammation and hepatocyte necrosis [2,26]. The aim of this study is to establish a non-radioactive method, i.e. enzyme-linked immunosorbent assay (ELISA) to evaluate serum PIIINP using BDL/s-and DMN-induced hepatic fibrosis in rats. MATERIALS AND METHODS Animals:Two hundred male Sprague-Dawley rats (11 weeks old) obtained from Laboratory Animal Center of Seoul National University in Korea were used. The animals were kept in an animal room maintained at 23 ± 2°C with 60 ± 10% r.h. with 12 hr-light and 12 hr-dark cycle, and were given normal pelleted diet (Shinchon, Korea) and water ad libitum.Treatments: As to bile duct ligation/scission (BDL/s) model, the hepatic biliary system was occluded by distal and proximal ligation using 4-0 silk (P...

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Section: Discussionmentioning

confidence: 93%

“…However, because of several reasons, e.g. a significant sampling error [1] and an ethical problem of continuous biopsies [8], a reliable serum assay for hepatic fibrosis is needed urgently. For decades, many kinds of serum assay for ECM components have been studied and used to diagnose liver diseases.…”

Section: Discussionmentioning

confidence: 99%

Enzyme-Linked Immunosorbent Assay for Serum Procollagen Type III Peptide in Rats with Hepatic Fibrosis.

Cho

Lee

1998

The Journal of Veterinary Medical Science

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“…All bile duct surgery was performed with an op-monospecific rabbit antiserum to PIIINP and a goat antiserum to erating microscope (OPMI 6-S, Zeiss, Germany). 3 Following BDO, rabbit IgG, as described previously. 3,19,21 Inter-and intra-assay coefanimals received normal chow (Altromin, Lage, Germany) and wa-ficients of variation were 12% and 4% for a normal sample, and 4% ter ad libitum.…”

Section: 2mentioning

confidence: 99%

Silymarin retards collagen accumulation in early and advanced biliary fibrosis secondary to complete bile duct obliteration in rats

et al. 1997

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rate hepatic collagen accumulation even in advanced (biliary) Silymarin (SIL), a standardized plant extract containing fibrosis; and 3) PIIINP appears to be a suitable serum marker about 60% polyphenole silibinin, is used as a hepatoprotective to monitor the inhibition of hepatic fibrogenesis in this model agent. Its antifibrotic potential in chronic liver diseases has of biliary fibrosis. (HEPATOLOGY 1997;26:643-649.) not been explored. Therefore, we applied SIL to adult Wistar rats that were subjected to complete bile duct occlusion (BDO) by injection of sodium amidotrizoate (Ethibloc). ThisProven therapy that halts the progression of liver fibrosis treatment induces progressive portal fibrosis without signifior induces regression of established cirrhosis is urgently cant inflammation. Rats with sham-operation that received needed. For several reasons, such therapy is not available: SIL at 50 mg/kg/d (n Å 10) and rats with BDO alone (n Å 1) the evolution of fibrosis in man is usually slow; 2) fibrosis 20) served as controls, whereas groups of 20 animals were is difficult to quantify from needle biopsies; 3) sampling error fed SIL at a dose of 25 and 50 mg/kg/d during weeks 1 through poses a severe problem in small tissue specimens; and 4) 6 or doses of 50 mg/kg/d during weeks 4 through 6 of BDO.suitable animal models that mirror at least a subgroup of Animals were sacrificed after 6 weeks for determination of human chronic liver diseases are lacking. Serum markers blood chemistries, total and relative liver collagen (as hyof liver fibrosis that could be used as suitable noninvasive droxyproline [HYP]), and the serum aminoterminal propeppredictors of the enhanced synthesis and deposition of hetide of procollagen type III (PIIINP). BDO in untreated rats patic collagen, i.e., fibrogenesis, or its removal, i.e., fibrolysis, caused an almost ninefold increase in total liver collagen (16.1 would be an attractive alternative for monitoring patients { 3.1 vs. 1.8 { 0.4 mg HYP, P õ .001). SIL at 50 mg/kg/d under therapy with a potential antifibrotic agent. However, reduced total HYP by 30% to 35%, either when given from final proof that such parameters are clinically useful, alweek 1 through 6 or from week 4 through 6 after BDO (10. 6 though suggested in several recent reports, is still needed.1,2 { 2.7 and 10.2 { 3.9 mg HYP, both P õ .01 vs. BDO alone), For these reasons, we selected and improved the rat model whereas 25 mg/kg/d were ineffective. Because SIL at 50 mg/ of biliary fibrosis secondary to bile duct obstruction (BDO). kg/d also reduced the collagen content per gram of liver tissue, This model can induce progressive portal fibrosis and finally it acted as a true antifibrotic agent. The single value of PIIINP cirrhosis, being almost devoid of the generation of toxic radiat killing paralleled the antifibrotic activity of SIL with 11.6 cals, massive hepatocyte necrosis, or major inflammation. It { 3.8 and 9.9 { 3.7 vs. 15.3 { 5.2 mg/L in both high-dose therefore resembles human (biliary) liver fibrosis and allo...

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“…The hydroxyproline content in liver was measured as per the instruction provided byJamall et al 16,17 …”

Section: Assessment Of Hydroxyproline Content (Mg/g Liver)mentioning

confidence: 99%

Chemical bile duct embolization for chemical hepatectomy, long term efficacy and feasibility in rats

et al. 2016

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Background:Hepatolithiasis is the presence of calculi within the intrahepatic bile ducts. It represents a significant problem in hepatobiliary surgery because of its high recurrence rate and the associated intra-operative and post-operative risks. This study was designed to explore the long-term efficacy of chemical biliary duct embolization (CBDE) to treat recurrent hepatolithiasis and to explain the mechanism of CBDE. Aims and Objectives: To investigate the long term efficacy of chemical bile duct embolization (CBDE) on the targeted hepatic lobe and to explain the mechanism of CBDE to achieve chemical hepatectomy. Materials and Methods: The median biliary duct of rats were embolized with phenol and N-butylcyanoacrylate. The short-term (6 weeks) and long-term (12 weeks) effects of chemical bile duct embolization were compared by observing the degree of atrophy, fibrosis, and proliferation of collagen fibers and apoptosis of hepatocytes of the embolized hepatic lobe. The feasibility and effectiveness of chemical hepatectomy were analyzed by histology, Western blot analysis of collagen I fibers and assessment of hydroxyproline content. Results: After 6 weeks of the procedure, destruction of hepatocytes, fibrosis and "self-cut" was seen only in the periphery of the targeted hepatic lobe. Whereas after 12 weeks, complete destruction of hepatocytes, and replacement with proliferative bile ductules and collagen fibers leading to complete fibrosis and "self-cut" phenomenon in the whole targeted hepatic lobe was seen. Collagen I expression in the 6-weeks treatment group and 12-weeks treatment groups were 4 times and 12 times higher than that in the Sham operated (SO) group respectively (P<0.05). In addition, there was increase in hepatic hydroxyproline content (HYP) approximately by sevenfold in 6-weeks treatment group and twentyfold in 12-weeks treatment group after CBDE, when compared to that in the SO group (P<0.05). Conclusion: Chemical bile duct embolization can achieve ideal effect of chemical hepatectomy in the whole targeted lobe.

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Elevated serum aminoterminal procollagen type-III-peptide parallels collagen accumulation in rats with secondary biliary fibrosis

Cited by 39 publications

References 26 publications

Enzyme-Linked Immunosorbent Assay for Serum Procollagen Type III Peptide in Rats with Hepatic Fibrosis.

Enzyme-Linked Immunosorbent Assay for Serum Procollagen Type III Peptide in Rats with Hepatic Fibrosis.

Silymarin retards collagen accumulation in early and advanced biliary fibrosis secondary to complete bile duct obliteration in rats

Chemical bile duct embolization for chemical hepatectomy, long term efficacy and feasibility in rats

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