title: Role of ursodeoxycholic acid in prevention of methotrexate-induced liver toxicity.
abstract: OBJECTIVE
  Methotrexate (MTX)-induced hepatotoxicity restricts the clinical use of this immunosuppressive drug. In this study, our aim was to research the role of oxidative stress in the hepatic toxicity of MTX and the protective effect of ursodeoxycholic acid (UDCA) in this setting.
  
  
  METHODS
  Wistar type rats (n = 32) were divided into four groups; group-1 as the MTX + UDCA, group-2 as the MTX, group-3 as the UDCA, group-4 as the saline-receiving groups. The MTX + UDCA and MTX groups of rats received 50 mg/kg of UDCA administered orally; whilst physiological saline was administered orally to the MTX and saline groups and continued for the next 6 days. On the second day of the study, the MTX + UDCA and MTX groups had a single intraperitoneal dose of MTX of 20 mg/kg. The UDCA and saline groups also received similar volumes of physiological saline intraperitoneally. On the sixth day, serum samples were collected and analyzed for ALT, alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) and homogenated liver tissues were examined for reactive oxygen metabolites (ROM); luminol, lucigenin, lipid peroxygenation product malondialdehyde (MDA) and glutathione (GSH) levels.
  
  
  RESULTS
  In the MTX group, serum ALT, ALP, GGT and tissue ROM levels were higher and GSH level was lower. On the histopathological examination, hepatocellular necrosis was clearly more evident in the MTX group than the MTX + UDCA group.
  
  
  CONCLUSIONS
  UDCA treatment protects against MTX-induced liver toxicity. Histopathologically hepatocyte necrosis can be prevented by UDCA treatment, indicating clearly the hepatoprotective effect of this agent on MTX-induced liver injury.
authors.affiliation: Department of Gastroenterology, Kocaeli University Medical Faculty, Kocaeli, Turkey.
authors.forename: Suleyman
authors.initials: S
authors.lastname: Uraz
authors.forename: Veysel
authors.initials: V
authors.lastname: Tahan
authors.forename: Cem
authors.initials: C
authors.lastname: Aygun
authors.forename: Fatih
authors.initials: F
authors.lastname: Eren
authors.forename: Goksenin
authors.initials: G
authors.lastname: Unluguzel
authors.forename: Meral
authors.initials: M
authors.lastname: Yuksel
authors.forename: Omer
authors.initials: O
authors.lastname: Senturk
authors.forename: Erol
authors.initials: E
authors.lastname: Avsar
authors.forename: Goncagul
authors.initials: G
authors.lastname: Haklar
authors.forename: Cigdem
authors.initials: C
authors.lastname: Celikel
authors.forename: Sadettin
authors.initials: S
authors.lastname: Hulagu
authors.forename: Nurdan
authors.initials: N
authors.lastname: Tozun
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015227:Lipid Peroxidation / Q000502:physiology; D008107:Liver Diseases / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D002756:Cholagogues and Choleretics; D007166:Immunosuppressive Agents; D014580:Ursodeoxycholic Acid; D008727:Methotrexate