Beraprost sodium, a prostacyclin (PGI2) analogue, ameliorates concanavalin A-induced liver injury in mice

Satoshi Ohta, Makoto Nakamuta, Marie Fukushima, Motoyuki Kohjima, Kazuhiro Kotoh, Munechika Enjoji, Hajime Nawata

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Abstract

Background/Aims: Prostacyclin (PGI2) is a potent mediator in the inflammatory and coagulation processes. The aim of this study was to test whether beraprost sodium, a PGI2 analogue, could prevent experimental hepatic injury induced by concanavalin A (Con A), which is a model of fulminant hepatic failure. Methods: Beraprost (100 μg/kg) was administered intraperitoneally simultaneously with Con A (40 mg/kg) in C57B6J mice. Blood circulation in the liver was determined by laser-Doppler flowmetry. Plasma levels of alanine aminotransferase (ALT), tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-6 were determined. Levels of TNF-α and IFN-γ in culture supernatant of splenocytes were also determined. Results: Beraprost administration reduced the incidence of death following hepatic failure (76.5% vs. 29.4%, P<0.05). Plasma levels of ALT were significantly lower in the beraprost-treated group than in the control group, and in the former, there was concomitant suppression of the histological features of injury. Beraprost significantly increased hepatic blood flow volume in Con A-treated mice. Plasma levels of TNF-α and IFN-γ were significantly reduced at 6 and 12h after Con A injection, respectively, but the levels of IL-6 were increased at 6h. In vitro, beraprost also suppressed Con A-induced TNF-α production in splenocytes, while it stimulated IFN-γ production. Conclusion: These findings imply that beraprost suppresses Con A-induced liver injury. These data also suggest that beraparost, which is clinically effective in treating pulmonary hypertension, may have therapeutic potential for preventing hepatic injury.

Original languageEnglish
Pages (from-to)1061-1068
Number of pages8
JournalLiver International
Volume25
Issue number5
DOIs
Publication statusPublished - Oct 1 2005

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All Science Journal Classification (ASJC) codes

  • Hepatology

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