1. Volume 118, Issue 6, Pages 1169-1178 (June 2000)
An oral endothelin-A receptor antagonist blocks collagen synthesis and deposition in advanced rat liver fibrosis 
Jae-Jin Cho, Berthold Hocher, Hermann Herbst, Ji-Dong Jia, Martin Ruehl, Eckhart G. Hahn, Ernst Otto Riecken, Detlef Schuppan 
Gastroenterology 
Volume 118, Issue 6, Pages (June 2000)
DOI: /S (00)
Copyright © 2000 American Gastroenterological Association Terms and Conditions

2. Fig. 1
Study design and histological stages of of rat livers. (A) Experimental design. LU , LU , and LU : rats with BDO (■) treated with LU at 80 mg · kg−1 · day−1 from week 4 to 6 (▧), at 80 mg · kg−1 · day−1 from week 1 to 6 (▧), or 10 mg · kg−1 · day−1 from week 1 to 6 (□), respectively. Rats without BDO and no treatment for 6 weeks (n = 10) or with sham operation and daily treatment with LU at 80 mg · kg−1 · day−1 for 6 weeks (Sham) served as controls. (B-E) Staging of liver fibrosis after Masson trichrome staining. (B) Stage I: BDO with LU at 80 mg · kg−1 · day−1 for 6 weeks; (C) stage II: BDO with LU at 10 mg · kg−1 · day−1 for 6 weeks; (D) stage III: BDO with LU at 80 mg · kg−1 · day−1 from week 4 to 6; (E) stage IV: BDO without treatment.
Gastroenterology  , DOI: ( /S (00) )
Copyright © 2000 American Gastroenterological Association Terms and Conditions

3. Fig. 1
Study design and histological stages of of rat livers. (A) Experimental design. LU , LU , and LU : rats with BDO (■) treated with LU at 80 mg · kg−1 · day−1 from week 4 to 6 (▧), at 80 mg · kg−1 · day−1 from week 1 to 6 (▧), or 10 mg · kg−1 · day−1 from week 1 to 6 (□), respectively. Rats without BDO and no treatment for 6 weeks (n = 10) or with sham operation and daily treatment with LU at 80 mg · kg−1 · day−1 for 6 weeks (Sham) served as controls. (B-E) Staging of liver fibrosis after Masson trichrome staining. (B) Stage I: BDO with LU at 80 mg · kg−1 · day−1 for 6 weeks; (C) stage II: BDO with LU at 10 mg · kg−1 · day−1 for 6 weeks; (D) stage III: BDO with LU at 80 mg · kg−1 · day−1 from week 4 to 6; (E) stage IV: BDO without treatment.
Gastroenterology  , DOI: ( /S (00) )
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4. Fig. 2
Antifibrotic effect of the oral ETAR antagonist in rat biliary fibrosis. (A) Total and (B) relative liver collagen content was quantitated after hydrolysis of liver samples and biochemical determination of HYP; (C) the serum level of PIIINP at week 6 served as surrogate marker of hepatic fibrogenesis. Control, rats without treatment for 6 weeks; Sham, sham operation and daily treatment with LU at 80 mg · kg−1 · day−1 for 6 weeks; BDO, BDO alone; LU/4-6, LU/1-6, and Low, rats with BDO that received LU at 80 mg · kg−1 · day−1 from week 4 to 6, at 80 mg · kg−1 · day−1 from week 1 to 6, or at 10 mg · kg−1 · day−1 from week 1 to 6, respectively. Values are means ± SD. *P < 0.05; **P < 0.001, ***P < vs. BDO alone.
Gastroenterology  , DOI: ( /S (00) )
Copyright © 2000 American Gastroenterological Association Terms and Conditions

5. Fig. 3
Kidney histology of LU (LU) treated rats. (A) Sham-operated rats treated with LU at 80 mg · kg−1 · day−1 for 6 weeks; (B) rats with BDO alone for 6 weeks (BDO) and (C) rats with BDO that were fed LU at 80 mg · kg−1 · day−1 for 6 weeks. In all BDO rats that received high-dose LU, but in none of the animals that received low dose LU, clear signs of tubular necrosis were observed, such as cholesterol crystals (thin arrow), granular cylinders (thick arrow), and necrotic tubular epithelial cells (arrowhead).
Gastroenterology  , DOI: ( /S (00) )
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6. Fig. 4
The ETAR antagonist suppresses hepatic collagen accumulation by down-regulation of procollagen α1(I) and TIMP-1 mRNA. Multiprobe ribonuclease protection assay. (A) Autoradiography and (B) relative abundance of procollagen α1(I) and TIMP-1 mRNA in rat livers (n = 5 of each group); tRNA, negative control containing transfer RNA; control, sham operation and LU at 80 mg · kg−1 · day−1 for 6 weeks; BDO, BDO alone; LU, BDO and LU at 80 mg · kg−1 · day−1 for 6 weeks; Pro α1(I), procollagen α1(I). *P < 0.05 vs. BDO alone.
Gastroenterology  , DOI: ( /S (00) )
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7. Fig. 5
Correlation of serum PIIINP and hepatic procollagen α1(I) and TIMP-1 levels. Serum PIIINP was determined from blood obtained during sacrifice and correlated with the hepatic steady state levels of (A) procollagen mRNA α1(I) and (B) TIMP-1 mRNA. R, linear regression correlation (Pearson correlation coefficient; P < for both correlations). Total number of paired samples: n = 29 (unoperated controls, n = 10; BDO alone, n = 10; LU at 80 mg · kg−1 · day−1 for 6 weeks, n = 9). Values are means ± SD.
Gastroenterology  , DOI: ( /S (00) )
Copyright © 2000 American Gastroenterological Association Terms and Conditions

8. Fig. 5
Correlation of serum PIIINP and hepatic procollagen α1(I) and TIMP-1 levels. Serum PIIINP was determined from blood obtained during sacrifice and correlated with the hepatic steady state levels of (A) procollagen mRNA α1(I) and (B) TIMP-1 mRNA. R, linear regression correlation (Pearson correlation coefficient; P < for both correlations). Total number of paired samples: n = 29 (unoperated controls, n = 10; BDO alone, n = 10; LU at 80 mg · kg−1 · day−1 for 6 weeks, n = 9). Values are means ± SD.
Gastroenterology  , DOI: ( /S (00) )
Copyright © 2000 American Gastroenterological Association Terms and Conditions