The selenoorganic compound ebselen suppresses liver injury induced by Propionibacterium acnes and lipopolysaccharide in rats

  • Authors:
    • Toshimasa Koyanagi
    • Makoto Nakamuta
    • Munechika Enjoji
    • Hiroaki Iwamoto
    • Kenta Motomura
    • Hironori Sakai
    • Hajime Nawata
  • View Affiliations

  • Published online on: March 1, 2001     https://doi.org/10.3892/ijmm.7.3.321
  • Pages: 321-327
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Abstract

Ebselen (2-phenyl-1,2-benzoisoselenazol-3[2H]-one) is a selenoorganic compound containing selenium that has various pharmacological effects, including anti-inflammatory and antioxidant activity. Kupffer cells, residual hepatic macrophages, play an important role in the development of liver injury by producing free radicals and cytokines. The aim of this study is to evaluate whether ebselen suppresses macrophage-associated liver injury in rats. In vivo, we examined the effects of ebselen on liver injury, induced by Propionibacterium acnes and lipopolysaccharide (P. acnes-LPS), in rats where hepatic macrophages are considered to be primarily involved in injury development. Ebselen administration reduced the incidence of death following hepatic failure by P. acnes-LPS (82% vs. 20%, p<0.05). Serum levels of alanine aminotransferase, at 5 h after LPS administration, were significantly lower in the ebselen-treated group than in the control group (202.4±100.3 IU/l vs. 558.4±146.4 IU/l, p<0.05). Histological evidence of injury, such as necrosis, hemorrhage, and degeneration, was also suppressed by ebselen. Further, to assess the mechanisms involved, we investigated the production of cytokines and superoxide anions produced by activated hepatic macrophages in vivo. Serum levels of TNFα, interleukin-18 (IL-18)/IFNγ-inducing factor (IGIF), and interferon γ (IFNγ) at 1 h after LPS administration were significantly lower in the ebselen-treated group. Formazan depositions, which were generated by the perfusion of the liver with nitroblue tetrazolium, were also observed less frequently in the ebselen treated group, suggesting a suppression in the release of superoxide anion from activated hepatic macrophages. In addition, we examined the effects of ebselen on cytokine production and mRNA expression, in vitro, using rat primary Kupffer cell culture. Ebselen also inhibited TNFα production and mRNA expression in vitro. These data imply that ebselen suppresses liver injury by inhibiting the production and/or release of proinflammatory cytokines and superoxide from activated hepatic macrophages. These data also suggest that ebselen is potent in the prevention of hepatic injury, such as endotoxemia, where hepatic macrophage activation has been implicated.

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March 2001
Volume 7 Issue 3

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

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Spandidos Publications style
Koyanagi T, Nakamuta M, Enjoji M, Iwamoto H, Motomura K, Sakai H and Nawata H: The selenoorganic compound ebselen suppresses liver injury induced by Propionibacterium acnes and lipopolysaccharide in rats. Int J Mol Med 7: 321-327, 2001
APA
Koyanagi, T., Nakamuta, M., Enjoji, M., Iwamoto, H., Motomura, K., Sakai, H., & Nawata, H. (2001). The selenoorganic compound ebselen suppresses liver injury induced by Propionibacterium acnes and lipopolysaccharide in rats. International Journal of Molecular Medicine, 7, 321-327. https://doi.org/10.3892/ijmm.7.3.321
MLA
Koyanagi, T., Nakamuta, M., Enjoji, M., Iwamoto, H., Motomura, K., Sakai, H., Nawata, H."The selenoorganic compound ebselen suppresses liver injury induced by Propionibacterium acnes and lipopolysaccharide in rats". International Journal of Molecular Medicine 7.3 (2001): 321-327.
Chicago
Koyanagi, T., Nakamuta, M., Enjoji, M., Iwamoto, H., Motomura, K., Sakai, H., Nawata, H."The selenoorganic compound ebselen suppresses liver injury induced by Propionibacterium acnes and lipopolysaccharide in rats". International Journal of Molecular Medicine 7, no. 3 (2001): 321-327. https://doi.org/10.3892/ijmm.7.3.321