title: Antidiabetic drug metformin is effective on the metabolism of asymmetric dimethylarginine in experimental liver injury.
abstract: OBJECTIVE
  We aimed to investigate the pharmacological efficiency of metformin on asymmetric dimethylarginine (ADMA) metabolism in inflammation caused by the lipopolysaccharide (LPS)/D-galactosamine (D-GalN) treatment.
  
  
  METHODS
  Adult Sprague-Dawley rats were injected LPS/D-GalN intraperitoneally. One half of the animals was injected metformin (250 mg kg(-1) body mass for one week) prior to LPS/D-GalN treatment. Six hours after the LPS/D-GalN injection, livers were removed, and used for the measurements of dimethylarginine dimethylaminohydrolase (DDAH) and myeloperoxidase (MPO) activities, glutathione (GSH), ADMA and arginine levels. Liver tissues were examined histopathologically. The Kruskal-Wallis (posthoc Mann-Whitney U) test was used for the statistics. LPS/D-GalN injections caused liver injury as evidenced by the activities of aminotransferases and arginase. GSH level and DDAH activity were decreased in the liver. Metformin pretreatment alleviated the activity of serum enzymes, and attenuated histopathological lesions caused by LPS/D-GalN injections. LPS/D-GalN-induced inflammation, as confirmed by the increased MPO activity, created an asymmetrical distribution of arginine and ADMA between the tissue and plasma. Metformin decreased tissue ADMA level while it restored the DDAH activity and GSH.
  
  
  CONCLUSIONS
  Our findings showed that metformin administration for one week has a potency to protect liver through regulating ADMA metabolism in LPS/D-GalN-induced injury.
authors.affiliation: Istanbul University, Istanbul Faculty of Medicine, Department of Biochemistry, Capa, Istanbul 34093, Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Bal
authors.affiliation: Istanbul University, Istanbul Faculty of Medicine, Department of Biochemistry, Capa, Istanbul 34093, Turkey.
authors.forename: Seldag
authors.initials: S
authors.lastname: Bekpinar
authors.affiliation: Istanbul University, Istanbul Faculty of Medicine, Department of Biochemistry, Capa, Istanbul 34093, Turkey.
authors.forename: Yesim
authors.initials: Y
authors.lastname: Unlucerci
authors.affiliation: Istanbul University, Istanbul Faculty of Medicine, Department of Biochemistry, Capa, Istanbul 34093, Turkey.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Kusku-Kiraz
authors.affiliation: Istanbul University, Istanbul Faculty of Medicine, Department of Pathology, Capa, Istanbul 34093, Turkey.
authors.forename: Semen
authors.initials: S
authors.lastname: Önder
authors.affiliation: Istanbul University, Istanbul Faculty of Medicine, Department of Biochemistry, Capa, Istanbul 34093, Turkey.
authors.forename: Mujdat
authors.initials: M
authors.lastname: Uysal
authors.affiliation: Istanbul University, Istanbul Faculty of Medicine, Department of Biochemistry, Capa, Istanbul 34093, Turkey. Electronic address: figur@istanbul.edu.tr.
authors.forename: Figen
authors.initials: F
authors.lastname: Gurdol
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005688:Galactosamine; D005978:Glutathione / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008070:Lipopolysaccharides; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D009195:Peroxidase / Q000378:metabolism; D020011:Protective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007004:Hypoglycemic Agents; D008070:Lipopolysaccharides; D020011:Protective Agents; C018524:N,N-dimethylarginine; D005688:Galactosamine; D008687:Metformin; D001120:Arginine; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000581:Amidohydrolases; C059999:dimethylargininase; D005978:Glutathione
keywords: Arginine; Asymmetric dimethylarginine; Dimethylarginine dimethylaminohydrolase; Inflammation; Liver injury; Metformin