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Increases in fibrosis-related gene transcripts in livers of dimethylnitrosamine-intoxicated rats

  • Original Paper
  • Published:
Journal of Biomedical Science

Abstract

Fibrosis-related changes in livers of cirrhotic rats induced by dimethylnitrosamine (DMN) have not yet been fully clarified. The aim of this study was to investigate changes in molecular and biochemical markers in DMN-intoxicated rats. DMN was administered to Sprague-Dawley rats for 2 and 5 weeks to induce different degrees of hepatic fibrosis. Liver tissues were assessed for the degree of fibrosis and gene expression. Histological examination of the liver showed a progressive increase in fibrosis scores (1.33 ± 0.21 and 3.03 ± 0.29, respectively) and expansion of fibrous septa with collagen-staining fibers in rats after 2 and 5 weeks of DMN administration. Hepatic protein contents of α-smooth muscle actin (α-SMA) and total collagen were significantly higher in rats administered DMN for both 2 and 5 weeks compared with those in control rats. Hepatic mRNA expressions of α-SMA, transforming growth factor-β1 (TGF-β1), connective tissue growth factor, tissue inhibitor of metalloproteinase-1, and procollagen I and III were increased in DMN rats after 2 and 5 weeks. Abnormal increases in plasma alanine transaminase (ALT) and aspartate transaminase (AST) levels, plasma and mitochondrial MDA levels, and portal venous pressure were also noted in DMN rats. DMN administration to rats for 2 and 5 weeks induced progressive increases in hepatic fibrosis scores, hepatic mRNA expressions of TGF-β1 and procollagen I and III genes, plasma levels of ALT and AST, and portal venous pressure, as well as progressive decreases in both liver and body weights. Our results suggest that DMN administration in rats induces biochemical and molecular changes related to fibrogenesis in the liver.

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Authors and Affiliations

  1. Department of Education and Research, Taichung Veterans General Hospital, Taichung

    Yung-Tsung Chiu

  2. National Research Institute of Chinese Medicine, Taipei, Taiwan, ROC

    Yun-Lian Lin

  3. Institute of Traditional Medicine, National Yang-Ming University School of Medicine, No. 155 Li-Nong Street, Sec. 2, 112, Taipei, Taiwan (ROC)

    Yi-Chao Hsu, Chang-Yin Lee & Yi-Tsau Huang

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Hsu, YC., Chiu, YT., Lee, CY. et al. Increases in fibrosis-related gene transcripts in livers of dimethylnitrosamine-intoxicated rats. J Biomed Sci 11, 408–417 (2004). https://doi.org/10.1007/BF02254446

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