title: 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‑κB were observed. These data indicate that the LPS/D‑Gal‑induced elevation of the stable protein level of hypoxia inducible factor 1α, 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.
authors.affiliation: Department of Liver Diseases, Hepatology Center, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian 361000, P.R. China.
authors.forename: Xianqiong
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of General Surgery, The First People's Hospital of Jingmen, Jingmen, Hubei 448000, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Duan
authors.affiliation: Department of Pathology, The First People's Hospital of Jingmen, Jingmen, Hubei 448000, P.R. China.
authors.forename: Jin-E
authors.initials: JE
authors.lastname: Ao
authors.affiliation: Department of Physiology, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ai
authors.affiliation: Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Pu
authors.initials: P
authors.lastname: Ge
authors.affiliation: Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism; D005688:Galactosamine / Q000009:adverse effects*; D006505:Hepatitis / Q000188:drug therapy* / Q000209:etiology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C497443:Hif1a protein, mouse; D007004:Hypoglycemic Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; D019344:Lactic Acid; D005688:Galactosamine; D013925:Thromboplastin; D008687:Metformin; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse