Preventive effect of cyclosporin A on experimentally induced acute liver injury in rats

Authors

  • Shuji Wasaki,

    1. The First Department of Internal Medicine, Yamaguchi University, School of Medicine, Yamaguchi-Prefecture, Japan
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  • Isao Sakaida M.D.,

    Corresponding author
    1. The First Department of Internal Medicine, Yamaguchi University, School of Medicine, Yamaguchi-Prefecture, Japan
      The First Department of Internal Medicine, Yamaguchi University School of Medicine, Yamaguchi-Prefecture, 755, Japan
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  • Koichi Uchida,

    1. The First Department of Internal Medicine, Yamaguchi University, School of Medicine, Yamaguchi-Prefecture, Japan
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  • Teruaki Kimura,

    1. The First Department of Internal Medicine, Yamaguchi University, School of Medicine, Yamaguchi-Prefecture, Japan
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  • Kozo Kayano,

    1. The First Department of Internal Medicine, Yamaguchi University, School of Medicine, Yamaguchi-Prefecture, Japan
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  • Kiwamu Okita

    1. The First Department of Internal Medicine, Yamaguchi University, School of Medicine, Yamaguchi-Prefecture, Japan
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The First Department of Internal Medicine, Yamaguchi University School of Medicine, Yamaguchi-Prefecture, 755, Japan

Abstract

Abstract: We examined the effect of cyclosporin A (CsA) on the pathogenesis of acute experimental liver injury in rats induced by injection of heat-killed Propionibacterium acnes (P. acnes) and subsequent injection of lipopolysaccharide (LPS). Pretreatment with CsA significantly reduced serum alanine aminotransferase (ALT), serum tumor necrosis factor-α (TNF-α) production, without changing the TNF-α mRNA level in the liver, and plasma interferon-γ (IFN-γ), following LPS injection in this model. Twenty-four-hour mortality was also markedly improved, from 100% in the P. acnes plus LPS group to 0% in the CsA-pretreated group. Although direct addition of CsA to isolated hepatic macrophages from P. acnes-pretreated rats did not prevent the production of TNF-α and active oxygen species, isolated hepatic macrophages from P. acnes plus CsA-pretreated rats significantly reduced their production in response to the addition of LPS. These results suggest that CsA protects against P. acnes plus LPS-induced acute liver injury, not by direct inhibition of hepatic macrophage activation, but by indirect prevention of hepatic macrophage activation, presumably related to the reduction in plasma IFN-γ levels.

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