title: Effect of rosiglitazone on asymmetric dimethylarginine metabolism in thioacetamide-induced acute liver injury.
abstract: Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, is metabolized in the liver by dimethylarginine dimethylaminohydrolase (DDAH). We aimed to investigate the effect of rosiglitazone, a peroxysome proliferator-activated receptor-gamma (PPAR-γ) agonist, on ADMA metabolism in acute liver injury. Male Sprague Dawley rats were injected thioacetamide (TAA; 500mgkg(-1)) intraperitoneally in order to induce acute liver injury. ADMA, SDMA and arginine levels were determined in plasma by the HPLC. Liver DDAH activity and malondialdehyde (MDA) levels were measured by spectrophotometric procedures. TAA injection caused marked increases in ALT and AST activities. Plasma ADMA levels were increased, while arginine levels and arginine/ADMA ratio were decreased. Liver DDAH activity was significantly diminished and MDA levels were elevated. In another group of animals which were treated with a PPAR-γ agonist (rosiglitazone, 5mgkg(-1)) daily via gastric intubation for a week prior to TAA injection, significant recoveries in DDAH activity and antioxidant status were observed when compared with solely TAA-injected animals. Rosiglitazone pretreatment improved the plasma arginine/ADMA ratio. Our findings indicated that PPAR-γ agonist rosiglitazone beneficially influenced hepatic metabolism of ADMA in TAA-induced acute liver damage.
authors.affiliation: Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Capa, 34093, Istanbul, Turkey. Electronic address: seldabekpinar@hotmail.com.
authors.forename: Seldag
authors.initials: S
authors.lastname: Bekpinar
authors.affiliation: Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Capa, 34093, Istanbul, Turkey.
authors.forename: Duygu
authors.initials: D
authors.lastname: Vardagli
authors.affiliation: Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Capa, 34093, Istanbul, Turkey.
authors.forename: Yesim
authors.initials: Y
authors.lastname: Unlucerci
authors.affiliation: Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Capa, 34093, Istanbul, Turkey.
authors.forename: Ayten
authors.initials: A
authors.lastname: Can
authors.affiliation: Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Capa, 34093, Istanbul, Turkey.
authors.forename: Mujdat
authors.initials: M
authors.lastname: Uysal
authors.affiliation: Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Capa, 34093, Istanbul, Turkey.
authors.forename: Figen
authors.initials: F
authors.lastname: Gurdol
keywords: Acute liver injury; Asymmetric dimethylarginine; Dimethylarginine dimethylaminohydrolase; PPAR-γ agonists; Rosiglitazone