Metformin suppresses intrahepatic coagulation activation in mice with lipopolysaccharide/D-galactosamine-induced fulminant hepatitis

Abstract

Metformin is a widely-used antidiabetic drug with hypoglycemic activity and previously described anti-inflammatory properties-Previous studies have demonstrated that metformin attenuates endotoxic hepatitis, however the mechanisms remain unclear-Inflammation and coagulation are closely associated pathological processes, therefore the potential effects of metformin on key steps in activation of the coagulation system were further investigated in endotoxic hepatitis induced by lipopolysaccharide/D-galactosamine (LPS/D-Gal)-The current study demonstrated that treatment with metformin significantly suppressed the upregulation of tissue factor and plasminogen activator inhibitor-1 in LPS/D-Gal-exposed mice-In addition, a reduction in the expression of interleukin-6 and inhibition of nuclear translocation of nuclear factor-αB were observed-These data indicate that the LPS/D-Gal-induced elevation of the stable protein level of hypoxia inducible factor-1, the mRNA level of erythropoietin, vascular endothelial growth factor and matrix metalloproteinase-3, and the hepatic level of lactic acid were also suppressed by metformin-The current study indicates that the suppressive effects of metformin on inflammation-induced coagulation may be an additional mechanism underlying the hepatoprotective effects of metformin in mice with LPS/D-Gal-induced fulminant hepatitis.