Provocation of massive hepatic necrosis by endotoxin after partial hepatectomy in rats

Deranged blood coagulation equilibrium as a factor of massive liver necrosis following endotoxin administration in partially hepatectomized rats

“…26 In these rats, massive liver necrosis develops until 5 hours following intravenous injection of endotoxin, even at a dose that is not harmful to normal rats. 3,26 We demonstrated that this necrosis was caused by microcirculatory disturbances as a result of fibrin deposition and endothelial cell injury in the hepatic sinusoids developing between 3 and 5 hours after endotoxin administration, and antithrombin III concentrate significantly attenuated the liver injury and blood coagulation disorder. 3 Activated Kupffer cells, but not neutrophils, seemed to contribute to the initiation of such microcirculatory disturbance, because suppression of Kupffer cell activation by gum arabic significantly attenuated liver injury, 3 while eradication of circulating neutrophils by a polyclonal antibody against neutrophils was not effective.…”

“…3,26 We demonstrated that this necrosis was caused by microcirculatory disturbances as a result of fibrin deposition and endothelial cell injury in the hepatic sinusoids developing between 3 and 5 hours after endotoxin administration, and antithrombin III concentrate significantly attenuated the liver injury and blood coagulation disorder. 3 Activated Kupffer cells, but not neutrophils, seemed to contribute to the initiation of such microcirculatory disturbance, because suppression of Kupffer cell activation by gum arabic significantly attenuated liver injury, 3 while eradication of circulating neutrophils by a polyclonal antibody against neutrophils was not effective. 6 Thus, targeted cells of activated Kupffer cells were determined to elucidate the mechanism of endotoxin-induced sinusoidal fibrin deposition in 70% hepatectomized rats in the present experiment.…”

“…These results suggest that fibrin deposition developing in 70% hepatectomized rats after endotoxin administration may be caused by deranged blood coagulation in the hepatic sinusoids through increasing tissue factor activity in Kupffer cells and minimal TFPI Massive liver necrosis develops after endotoxin administration in rats pretreated with heat-killed Propionibacterium acnes or those undergoing 70% liver resection as a result of microcirculatory disturbance caused by sinusoidal fibrin deposition. [1][2][3] In both models, Kupffer cells and hepatic macrophages are activated to provoke endothelial cell injury and fibrin deposition in the hepatic sinusoids. [2][3][4][5][6] However, an apparent difference exists in the stimulatory state of Kupffer cells and hepatic macrophages between both models, because activated Kupffer cells in the partial-hepatectomy model produced fewer cytotoxic mediators such as superoxide anions and tumor necrosis factor ␣ in response to endotoxin administration compared with activated hepatic macrophages in the P. acnes model, 6,7 although both cells can release a large amount of superoxide anions after stimulation with phorbol 12-myristate 13-acetate.…”

“…[1][2][3] In both models, Kupffer cells and hepatic macrophages are activated to provoke endothelial cell injury and fibrin deposition in the hepatic sinusoids. [2][3][4][5][6] However, an apparent difference exists in the stimulatory state of Kupffer cells and hepatic macrophages between both models, because activated Kupffer cells in the partial-hepatectomy model produced fewer cytotoxic mediators such as superoxide anions and tumor necrosis factor ␣ in response to endotoxin administration compared with activated hepatic macrophages in the P. acnes model, 6,7 although both cells can release a large amount of superoxide anions after stimulation with phorbol 12-myristate 13-acetate. 3,4 Northern blot analysis revealed that such difference resulted from expression of endotoxin receptors on the cells; P. acnes-treated rat liver showed increased mRNA expression of CD14, a receptor for lipopolysaccharide and its binding protein complex, compared with normal liver, while such expression was markedly reduced in partially hepatectomized rat liver.…”

The ileum positively regulates hepatic regeneration in rats

“…It was also shown that bacterial translocation occurs after major hepatic resection 22 . Endotoxins were shown to have a significant negative effect on liver regeneration after partial hepatectomy 23 . Thus, it is possible that the increase of endotoxins and bacteria into the portal blood, which has been demonstrated after intestinal and liver resection, could have affected liver regeneration.…”