Background/purpose: D-allose, a rare sugar, has been reported to inhibit segmented neutrophil production without causing any significant detrimental clinical effects. Our previous study demonstrated the immunosuppressive effect of D-allose in a rat model of liver transplantation. Neutrophils are closely involved in the process of hepatic ischemia/reperfusion (I/R) injury. One possible mechanism is the adherence of neutrophils to the hepatic sinusoidal endothelium following microcirculatory failure.
Methods: The present study investigated the effects of D-allose on the involvement of neutrophils, with particular emphasis to the microcirculation in a model of hepatic I/R. Ischemia was induced by occluding the hepatoduodenal ligament for 90 min. D-allose was infused 2 h before ischemia. Normal saline was infused in the control group. Liver tissue blood flow (LTBF) and portal venous flow (PVF) were measured before and after ischemia. Myeloperoxidase (MPO) and ATP were measured at, before inducing ischemia, at the end of ischemia, and at the end of 2-h reperfusion. Liver enzyme analysis and histology were done at the end of reperfusion. Post-reperfusion animal survival was followed for 15 days.
Results: D-allose significantly improved the liver hemodynamics and post-reperfusion animal survival, with a significant decrease in liver tissue MPO, liver enzymes, and the number of neutrophils. ATP level was improved significantly in the D-allose group. Histology revealed significant sinusoidal congestion and tissue necrosis after 2-h reperfusion in the control group.
Conclusions: D-allose exerted its protective effects against liver damage incurred when the liver was injured by warm ischemia and reperfusion mainly by the suppression of activated neutrophils.