Yuzo Ichikawa

Effects of arachidonic acid metabolites and interleukin-1 on platelet activating factor production by hepatic sinusoidal endothelial cells from mice

The effects of interleukin‐1 (IL‐1) and arachidonic acid metabolites, prostaglandin (PG) E1, leukotriene (LT) B4 and LTC4, on the amount of platelet activating factor (PAF) produced and released by mouse hepatic sinusoidal endothelial cells were investigated. When hepatic sinusoidal endothelial cells were incubated with 1 μg/mL of calcium ionophore (CaI) A23187, PAF production increased until 20 min after the start of incubation, but when the cells were incubated with PGE1 and CaI A23187, PAF production was significantly suppressed. On the other hand, when hepatic sinusoidal endothelial cells were incubated with IL‐1β, LTB4 or LTC4 alone, PAF production significantly increased compared with that of the cells incubated without these substances. However, when the cells were incubated with PGE1 alone or with IL‐1β, LTB4 or LTC4 and CaI A23187, these effects were not observed. These results indicated that PAF produced by hepatic sinusoidal endothelial cells is affected by IL‐1 and arachidonic acid metabolites, suggesting that immune and inflammatory reactions in these cells may be regulated by chemical mediators produced by the cells themselves.

Effects of irsoglandine maleate in an experimentally-induced acute hepatic failure model using mice.

SummaryWhen heat-killedPropionibacterium acnes was intravenously injected into mice followed by an intravenous injection of a small amount of Gram-negative lipopolysaccharide seven days later, most of the mice died of massive hepatic cell necrosis within 24 hours. However, when irsoglandine maleate, an antiulcer agent, was administered to mice during the period of experimental induction of acute hepatic failure, the survival rate, serum transaminase levels and histological changes of the liver remarkably improved. These results suggested that irsoglandine maleate may have protective effects on the liver in our experimentally-induced acute hepatic failure model using mice. Therefore, in the absence of a definitive therapy for fulminant hepatitis, irsoglandine maleate may be a promising therapeutic agent.

Effects of the polysaccharide chain of lipopolysaccharide in an experimental massive hepatic cell necrosis model.

When small amounts (1 microgram) of lipopolysaccharide (LPS) purified from Salmonella minnesota (SM) wild, SM R60 and SM R345 were intravenously injected into mice 7 days after heat-killed Propionibacterium acnes was intravenously injected, massive hepatic cell necrosis was induced and most of the mice died within 24 hours. However, when LPS from SM R345 treated galactosidase, SM R5 and SM R7 and lipid A from SM R595 were administered, the survival rate was much higher and no histological changes of the liver such as necrosis could be seen in any of the mice. In each of the LPS used in this study, the structure of the polysaccharide chain was different and it was shorter in the following order: SM wild----SM R60----SM R345----SM R345 treated with galactosidase----SM R5----SM R7----SM R595. This suggests that the polysaccharide chain of LPS plays an important role in the induction of massive hepatic cell necrosis in this experimental model.