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A natural process of cirrhosis resolution and deceleration of liver regeneration after thioacetamide withdrawal in a rat model

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Abstract

Characteristics of thioacetamide (TAA)-induced liver cirrhosis in rat was observed for 120 days after TAA withdrawal as part of the radiobiological study of partial liver irradiation on TAA-induced cirrhotic rats. The natural process focused on cirrhosis and regeneration was recorded as a baseline condition for the interpretation of the outcome of the partial liver irradiation study. Cirrhosis in rats was successfully induced by drinking 0.03% TAA water orally for 29 weeks with a modeling rate of 96%. After establishment of the cirrhosis model, the rats were observed for 120 days upon TAA withdrawal to investigate the dynamic changes of cirrhosis and regeneration. The following characteristics were observed: (1) Histological changes; (2) Liver functions; (3) Cirrhosis: trichrome stain, quantification of hydroxyproline in hydrolysed liver tissue and TGF-β1; (4) Liver regeneration: liver index, hepatocyte mitotic index (MI), hepatocyte proliferation index (PI) by flow cytometry, PCNA labeling index (LI) by IHC and expression of PCNA mRNA; and (5) Growth factors: serum HGF, VEGF, TGF-α, and IL-6. After TAA withdrawal, gradual improvement in liver functions was noted with decreases of ALT, AST, and ALP, and increase of PA. The resolution of cirrhosis was evident by histological improvement with attenuation of collagen fiber and decrease of TGF-β1 IHC index, and also decrease of trichrome stain and hydroxyproline content. However, cirrhosis was still existed on 120 days after TAA withdrawal. Significant deceleration of liver regeneration was demonstrated with TAA withdrawal, evidenced by decrease of MI and PI, reduced expression of PCNA mRNA and PCNA LI. In conclusion, upon TAA withdrawal hepatic cirrhosis was continuously resolved, but persisted up to 120 days, and liver regeneration was significantly decelerated.

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Acknowledgments

This study was supported by the National Science Foundation of China (Grant no. 30800279) and in part by Grant 2004-826 from the Ministry of Public Health, People’s Republic of China. Authors thank Shiang Jiin Leaw, M.D. for her assistance in the English editing of this article.

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Authors and Affiliations

  1. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, China

    Ke Gu, Jian-Dong Zhao, Zhi-Gang Ren, Ning-Yi Ma, Song-Tao Lai, Jin Liu & Guo-Liang Jiang

  2. Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China

    Jian Wang

  3. Department of Oncology, Shanghai Medical School, Fudan University, Shanghai, China

    Ke Gu, Jian-Dong Zhao, Zhi-Gang Ren, Ning-Yi Ma, Song-Tao Lai, Jian Wang, Jin Liu & Guo-Liang Jiang

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  1. Ke Gu
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  2. Jian-Dong Zhao
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Correspondence to Guo-Liang Jiang.

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Gu, K., Zhao, JD., Ren, ZG. et al. A natural process of cirrhosis resolution and deceleration of liver regeneration after thioacetamide withdrawal in a rat model. Mol Biol Rep 38, 1687–1696 (2011). https://doi.org/10.1007/s11033-010-0281-1

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  • DOI: https://doi.org/10.1007/s11033-010-0281-1

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