Volume 41, Issue 2, Pages 235-241 (August 2004) Treatment of thioacetamide-induced liver cirrhosis by the Ras antagonist, farnesylthiosalicylic acid  Shimon Reif, Hussein Aeed, Yael Shilo, Reuven Reich, Yoel Kloog, Young Oh Kweon, Rafael Bruck  Journal of Hepatology  Volume 41, Issue 2, Pages 235-241 (August 2004) DOI: 10.1016/j.jhep.2004.04.010

Fig. 1 Liver histology: (A) liver section showing cirrhosis induced after 12 weeks of TAA treatment. H&E, magnification ×80. (B) Liver section showing cirrhosis induced by 12 weeks of TAA administration, after 8 weeks of PBS treatment: no evidence of spontaneous regression. H&E, magnification ×80. (C) Significant regression of hepatic fibrosis in the cirrhotic rats treated with FTS for 8 weeks, after the induction of cirrhosis. H&E, magnification ×80. Journal of Hepatology 2004 41, 235-241DOI: (10.1016/j.jhep.2004.04.010)

Fig. 2 The low activity of MMP-2 and MMP-9 in normal livers (untreated animals) was significantly increased in cirrhotic rats treated with TAA for 12 weeks. Four and eight weeks after TAA discontinuation, MMP activity was decreased in both groups, but the activity of MMP-2 (A, B) and MMP-9 (C, D) in the livers of the FTS-treated rats was significantly higher compared to the PBS-treated rats. N=5 in each group, mean±SD, ∗∗P<0.01 compared to normal and to TAA+PBS. Journal of Hepatology 2004 41, 235-241DOI: (10.1016/j.jhep.2004.04.010)

Fig. 3 Examples of apoptotic cells by TUNEL assay: (A) negative control. (B) No TUNEL positive cells. Livers with cirrhosis induced after 12 weeks of TAA treatment. (C) TUNEL positive cell at the center of the field (deep blue nucleus). TAA 12 weeks+PBS for 8 weeks. (D) TUNEL positive cells at upper and lower ends of the field. TAA 12 weeks+FTS 8 weeks (×80). (D2): immunohistochemical staining for α smooth muscle actin, demonstrating that the TUNEL-positive cells represent activated HSC. Journal of Hepatology 2004 41, 235-241DOI: (10.1016/j.jhep.2004.04.010)

Fig. 4 Quantification of cell apoptotic figures during recovery from TAA-induced liver cirrhosis. Cell apoptotic figures were quantified in liver sections from the various treatment groups 8 weeks after TAA withdrawal. Mean±SD, n=3. Journal of Hepatology 2004 41, 235-241DOI: (10.1016/j.jhep.2004.04.010)

Fig. 5 The expression of TIMP-2 in the rat livers of the various groups was measured 4 and 8 weeks after TAA withdrawal in different groups of rats using RT-PCR. As shown, FTS administration caused a marked increase in the expression of TIMP-2, both after 4 and 8 weeks of TAA withdrawal compared to the control group treated with PBS (n=5, ∗P<0.01 compared to normal; ∗∗P<0.01 compared to TAA+PBS). Journal of Hepatology 2004 41, 235-241DOI: (10.1016/j.jhep.2004.04.010)