Therapeutic effects of angiotensin II type 1 receptor blocker, irbesartan, on non-alcoholic steatohepatitis using FLS-ob/ob male mice

  • Authors:
    • Jun Kato
    • Masahiko Koda
    • Manabu Kishina
    • Shiho Tokunaga
    • Tomomitsu Matono
    • Takaaki Sugihara
    • Masaru Ueki
    • Yoshikazu Murawaki
  • View Affiliations

  • Published online on: April 2, 2012     https://doi.org/10.3892/ijmm.2012.958
  • Pages: 107-113
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Abstract

Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of a metabolic syndrome characterized by accumulation of hepatic fat, inflammation and varying degrees of fibrosis. Angiotensin (AT)-II has been reported to play a role in the establishment of NASH. This study examined the effects of an AT-II receptor blocker, irbesartan, on NASH using fatty liver Shionogi (FLS)-ob/ob male mice as the closest animal model of human metabolic syndrome-related NASH. Irbesartan (30 mg/kg/day) was orally administered to FLS-ob/ob mice for 12 weeks (irbesartan group). The effects of irbesartan on steatohepatitis were examined using factors including steatosis, fibrosis, inflammation and oxidative stress. The areas of hepatic fibrosis and hepatic hydroxyproline content were significantly lower in the irbesartan group compared to controls. The areas of α-smooth muscle actin-positivity and F4/80-positive cells were significantly decreased in the irbesartan group. The percentage of 8-hydroxy-2-deoxyguanosine (8-OHdG)-positive cells and 8-OHdG DNA content were significantly decreased in the irbesartan group compared to controls. Levels of RNA expression for procollagen I, transforming growth factor β1, tumor necrosis factor-α, sterol regulatory element-binding protein 1c and fatty acid synthase were significantly lower in the irbesartan group compared to controls. In contrast, the gene expression of peroxisome proliferator activated receptor-α was significantly higher in the irbesartan group compared to controls. Irbesartan administration improved hepatic steatosis and attenuated the progression of hepatic fibrosis by inhibiting the activation of hepatic stellate cells and Kupffer cells and reducing oxidative stress.

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July 2012
Volume 30 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Kato J, Koda M, Kishina M, Tokunaga S, Matono T, Sugihara T, Ueki M and Murawaki Y: Therapeutic effects of angiotensin II type 1 receptor blocker, irbesartan, on non-alcoholic steatohepatitis using FLS-ob/ob male mice. Int J Mol Med 30: 107-113, 2012
APA
Kato, J., Koda, M., Kishina, M., Tokunaga, S., Matono, T., Sugihara, T. ... Murawaki, Y. (2012). Therapeutic effects of angiotensin II type 1 receptor blocker, irbesartan, on non-alcoholic steatohepatitis using FLS-ob/ob male mice. International Journal of Molecular Medicine, 30, 107-113. https://doi.org/10.3892/ijmm.2012.958
MLA
Kato, J., Koda, M., Kishina, M., Tokunaga, S., Matono, T., Sugihara, T., Ueki, M., Murawaki, Y."Therapeutic effects of angiotensin II type 1 receptor blocker, irbesartan, on non-alcoholic steatohepatitis using FLS-ob/ob male mice". International Journal of Molecular Medicine 30.1 (2012): 107-113.
Chicago
Kato, J., Koda, M., Kishina, M., Tokunaga, S., Matono, T., Sugihara, T., Ueki, M., Murawaki, Y."Therapeutic effects of angiotensin II type 1 receptor blocker, irbesartan, on non-alcoholic steatohepatitis using FLS-ob/ob male mice". International Journal of Molecular Medicine 30, no. 1 (2012): 107-113. https://doi.org/10.3892/ijmm.2012.958