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


CONCLUSIONS
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.
Ohta
Satoshi
S
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-5282, Japan.
Nakamuta
Makoto
M
Fukushima
Marie
M
Kohjima
Motoyuki
M
Kotoh
Kazuhiro
K
Enjoji
Munechika
M
Nawata
Hajime
H
D000818:Animals; D003208:Concanavalin A / Q000633:toxicity*; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008102:Liver Circulation / Q000187:drug effects; D017114:Liver Failure, Acute / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D009569:Nitric Oxide; C048081:beraprost; D007371:Interferon-gamma; D011464:Epoprostenol