Ethyl pyruvate prevents inflammatory factors release and decreases intestinal permeability in rats with D-galactosamine-induced acute liver failure

摘要

BACKGROUND: The  pathogenesis  and  progression  of  acute liver  failure  (ALF)  are  closely  associated  with  intestinal endotoxemia  because  of  the  high  permeability  of  the intestinal  wall.  Treatment  with  ethyl  pyruvate  (EP)  has  been shown  to  protect  liver  failure  effectively.  The  current  study aimed  to  explore  the  relationship  between  proinflammatory cytokines  and  intestinal  permeability,  and  to  investigate whether  EP  administration  might  prevent  the  release  of multiple  proinflammatory  cytokines  and  decrease  intestinal permeability and therefore, protect the liver from injury. METHODS:  The ALF model was induced by D-galactosamine in  rats.  The  rats  were  randomly  divided  into  control  (saline, i.p.),  model  (D-galactosamine,  1.2  g/kg,  i.p.),  prevention  [EP injection  (40  mg/kg)  2  hours  ahead  of  D-galactosamine]  and treatment groups (EP injection 2 hours after D-galactosamine). Samples were obtained at 12 and 24 hours after ALF induction, respectively.  The  histology  of  liver  and  intestinal  tissue  was accessed.  Serum  alanine  aminotransferase,  endotoxin,  D(-)-lactate,  diamine  oxidase  (DAO),  tumor  necrosis  factor-alpha (TNF-α),  interferon-γ  (IFN-γ)  and  high  mobility  group  box-1 (HMGB1) were evaluated. The survival of rats was also recorded. RESULTS: The  rats  in  model  group  showed  severe  damage  to liver  tissue  and  intestinal  mucosa  12  and  24  hours  after  ALF induction. EP significantly improved liver or intestinal injury. In  addition,  serum  endotoxin,  D(-)-lactate,  DAO,  TNF-α, IFN-γ  and  HMGB1  levels  were  significantly  increased  in  the model  group  compared  with  the  control  group.  There  was a  positive  correlation  between  intestinal  permeability  and proinflammatory  cytokines.  EP  significantly  reduced  serum endotoxin, D(-)-lactate, DAO, TNF-α, IFN-γ and HMGB1 levels. The median survival time was significantly prolonged in both prevention and treatment groups (126 and 120 hours compared with 54 hours in the model group). CONCLUSIONS: EP has protective and therapeutic effects on intestinal  mucosa.  EP  decreases  intestinal  permeability,  and inhibits the release of multiple proinflammatory cytokines in rats with ALF.