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

Abstract

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 microg/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)-alpha, interferon (IFN)-gamma, and interleukin (IL)-6 were determined. Levels of TNF-alpha and IFN-gamma 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-alpha and IFN-gamma 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-alpha production in splenocytes, while it stimulated IFN-gamma production.

CONCLUSION:

These findings imply that beraprost suppresses Con A-induced liver injury. These data also suggest that beraprost, which is clinically effective in treating pulmonary hypertension, may have therapeutic potential for preventing hepatic injury.

• Authors: Satoshi Ohta, Makoto Nakamuta, Marie Fukushima, Motoyuki Kohjima, Kazuhiro Kotoh, Munechika Enjoji, Hajime Nawata
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 25 Issue 5 Pg. 1061-8 (Oct 2005) ISSN: 1478-3223 [Print] United States
• PMID: 16162167 (Publication Type: Journal Article)

Chemical References

• Interleukin-6
• Tumor Necrosis Factor-alpha
• Concanavalin A
• Nitric Oxide
• beraprost
• Interferon-gamma
• Epoprostenol

Topics

• Animals
• Concanavalin A (toxicity)
• Epoprostenol (analogs & derivatives, therapeutic use)
• Interferon-gamma (biosynthesis, blood)
• Interleukin-6 (blood)
• Liver Circulation (drug effects)
• Liver Failure, Acute (drug therapy)
• Male
• Mice
• Mice, Inbred C57BL
• Nitric Oxide (biosynthesis)
• Spleen (cytology, metabolism)
• Tumor Necrosis Factor-alpha (analysis, biosynthesis)