AT III injection via the tail vein significantly reduced HO-1 expression levels compared with those in the control sellckchem group, and its expression was further reduced by AT III injection via the portal vein (Figure (Figure4B).4B). These observations suggest that AT III injection via the portal vein reduces intrahepatic hypoxia, probably by controlling the microcirculatory disturbances. Figure 4 Effects of antithrombin III on hepatic mRNA expression of lactate dehydrogenase and heme oxygenase-1. Hepatic mRNA expression of lactate dehydrogenase (LDH) (A) and heme oxygenase (HO)-1 (B) was determined by real-time polymerase chain reaction. Reactions … Portal vein injection of AT III injection improved activity of the deteriorated coagulation system Serum levels of FDPs are a marker for the extent of deterioration in the coagulation system in ALF[20,21].

Injection of AT III via the tail vein did not change FDP levels, whereas injection of AT III via the portal vein significantly reduced FDP levels compared with those in the control and tail vein groups (Figure (Figure5).5). Taken together, improvements in the coagulation system were only achieved by injecting AT III directly into the diseased liver. Figure 5 Effects of antithrombin III on serum fibrin degradation product levels. The serum fibrin degradation product (FDP) levels were determined 24 h after injection of lipopolysaccharide and D-galactosamine. Control: Untreated; TV: Antithrombin (AT) III injection … Effects of AT III on intrahepatic fibrin deposition Fibrin deposition in hepatic sinusoids has been observed in ALF.

It is recognized as a manifestation of disturbances in the intrahepatic coagulation system and is mainly caused by sinusoidal endothelial cell injury[22]. In our study, phosphotungstic acid-hematoxylin staining revealed that fibrin was diffusely deposited in the sinusoids in the control liver, suggesting intrahepatic coagulation (Figure (Figure6A).6A). In rats treated with AT III via the tail vein, hepatic fibrin deposition was reduced but it was still sparsely distributed (Figure (Figure6B).6B). Meanwhile, injection of AT III via the portal vein diminished fibrin deposition in the liver parenchyma, which suggests that it may affect the maintenance of the intrahepatic coagulation system (Figure (Figure6C6C). Figure 6 Effects of antithrombin III on hepatic phosphotungstic acid-hematoxylin staining.

To estimate the extent of intrasinusoidal coagulation, fibrin deposition was analyzed by phosphotungstic acid-hematoxylin staining (magnification, �� 400). Fibrin … DISCUSSION We demonstrated that directly injecting AT III into the portal vein improved Entinostat liver damage in a rat model of ALF induced by LPS and GalN. AT III injection via the portal vein suppressed the increases in serum ALT and inflammatory cytokine levels, and intrahepatic fibrin deposition, and reduced the mRNA expression of hypoxia-related genes associated with ALF.