title: Antidiabetic drug metformin alleviates endotoxin-induced fulminant liver injury in mice.
abstract: Metformin is a first-line antidiabetic drug in type 2 diabetes for its hypoglycemic activity, but recently researches also revealed the anti-inflammatory properties of metformin. In the present study, the pharmacological efficiency of metformin in lipopolysaccharide (LPS)-induced hepatic injury in D-galactosamine (D-Gal)-sensitized mice was investigated. We found that pretreatment with metformin significantly decreased serum ALT and AST levels in LPS/D-Gal-exposed mice. These were accomplished with improved histological alterations in liver sections, decreased myeloperoxidase (MPO) activity, reduced malondialdehyde (MDA) content in liver homogenates and increased survival rate of experimental animals. Metformin also markedly reduced hepatic TNF-α mRNA content and blood TNF-α level. Additional experiment showed that metformin significantly attenuated LPS/D-Gal-induced hepatic apoptosis as evidenced by decreased caspase activities in liver tissues and reduced number of TUNEL-positive cells in liver sections. Furthermore, therapeutic administration of metformin after LPS/D-Gal challenge also improved the survival rate of experimental animal. These results indicated that the hypoglycemic reagent metformin could also provide therapeutic benefits in endotoxin-induced hepatic injury, suggesting its pharmacological potential in inflammation-base disorders.
authors.affiliation: Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Yuan
authors.forename: Longjiang
authors.initials: L
authors.lastname: Li
authors.forename: Weiping
authors.initials: W
authors.lastname: Zheng
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Wan
authors.forename: Pu
authors.initials: P
authors.lastname: Ge
authors.forename: Hongzhong
authors.initials: H
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005688:Galactosamine; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008070:Lipopolysaccharides; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008687:Metformin / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D007004:Hypoglycemic Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D005688:Galactosamine; D008687:Metformin; D020169:Caspases