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Beraprost sodium, a prostacyclin (PGI 2 ) analogue, ameliorates concanavalin A‐induced liver injury in mice
Author(s) -
Ohta Satoshi,
Nakamuta Makoto,
Fukushima Marie,
Kohjima Motoyuki,
Kotoh Kazuhiro,
Enjoji Munechika,
Nawata Hajime
Publication year - 2005
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2005.01143.x
Subject(s) - prostacyclin , concanavalin a , liver injury , chemistry , medicine , sodium , pharmacology , endocrinology , biochemistry , in vitro , organic chemistry
Background/Aims: Prostacyclin (PGI 2 ) is a potent mediator in the inflammatory and coagulation processes. The aim of this study was to test whether beraprost sodium, a PGI 2 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 12 h after Con A injection, respectively, but the levels of IL‐6 were increased at 6 h. 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.