Figure 5

(a) Representative photomicrographs of hematoxylin and eosin staining of the liver sections ( × 40). C57BL/6 mice were subjected liver ischemia reperfusion after vehicle- or sphinganine-1-phosphate treatment (0.1 mg/kg i.v. immediately before reperfusion and 0.2 mg/kg s.c. 2 h after reperfusion). Necrotic hepatic tissue appears as light pink (^*) with inflammation/vascular congestion near the portal triad (arrow). Some mice were pretreated with PD98059 (PD, an inhibitor of MEK1 to inhibit ERK phosphorylation, 1 mg/kg, i.p., N=6) or with wortmannin (Wort, an inhibitor of PI3K to inhibit Akt phosphorylation, 1 mg/kg, i.p., N=6) 20 min before vehicle or sphinganine-1-phosphate treatment. Some mice were pretreated with pertussis toxin (PTX, 25 μg/kg, i.p.) 48 h before sphinganine-1-phosphate treatment. Photographs are representative of six independent experiments. (b). Summary of Suzuki liver injury scores (scale 0–12) from mice subjected to liver IR after vehicle or sphinganine-1-phosphate treatment. Mice pretreated with PD98059, wortmannin, or pertussis toxin showed increased indices of hepatic injury. ^*P<0.05 vs vehicle-treated IR group. ^#P<0.05 vs sphinganine-1-phosphate-treated hepatic IR group.