Recent evidences show that
osthole possesses anti-inflammatory properties and protective effects following
shock-like states, but the mechanism of these effects remains unknown. The
p38 mitogen-activated protein kinase (
p38 MAPK) pathway exerts anti-inflammatory effects in injury. The aim of this study was to investigate whether
p38 MAPK plays any role in the
osthole-mediated attenuation of hepatic injury after
trauma-
hemorrhage. Male Sprague-Dawley rats underwent
trauma-
hemorrhage (mean blood pressure maintained at approximately 35-40 mmHg for 90 minutes), followed by fluid
resuscitation. During
resuscitation, a single dose of
osthole (3 mg/kg, intravenously) with and without a
p38 MAPK inhibitor
SB-203580 (2 mg/kg, intravenously),
SB-203580 or vehicle was administered. Plasma
alanine aminotransferase (ALT) with
aspartate aminotransferase (AST) concentrations and various hepatic parameters were measured (nā=ā8 rats/group) at 24 hours after
resuscitation. The results showed that
trauma-
hemorrhage increased hepatic
myeloperoxidase activity,
intercellular adhesion molecule-1 and
interleukin-6 levels, and plasma ALT and AST concentrations. These parameters were significantly improved in the
osthole-treated rats subjected to
trauma-
hemorrhage.
Osthole treatment also increased hepatic phospho-p38 MAPK expression compared with vehicle-treated
trauma-hemorrhaged rats. Co-administration of
SB-203580 with
osthole abolished the
osthole-induced beneficial effects on the above parameters and hepatic injury. These results suggest that the protective effect of
osthole administration on alleviation of hepatic injury after
trauma-
hemorrhage, which is, at least in part, through
p38 MAPK-dependent pathway.