title: Pre-administration of turmeric prevents methotrexate-induced liver toxicity and oxidative stress.
abstract: BACKGROUND
  Methotrexate (MTX) is an antimetabolite broadly used in treatment of cancer and autoimmune diseases. MTX-induced hepatotoxicity limits its application. We investigated hepatoprotective effects of turmeric in MTX-induced liver toxicity.
  
  
  METHODS
  All experiments were performed on male Wistar albino rats that were randomly divided into six groups. Group one received saline orally for 30 days (control group), groups two and three received turmeric extract (100, 200 mg/kg respectively) orally for 30 days, group four received single dose, of MTX IP at day 30, groups five and six received turmeric extract 100 and 200 mg/kg orally respectively for 30 days and single dose of methoterxate IP (20 mg/kg) at day 30. Four days after MTX injection animals were sacrificed and evaluated. Blood ALT and AST (indicators of hepatocyte injury), ALP and bilirubin (markers of biliary function), albumin (reflect liver synthetic function) as well as the plasma TAS concentration (antioxidant defenses) were determined. The cellular antioxidant defense activities were examined in liver tissue samples using SOD, CAT, and GSH-Px for the oxidative stress, and MDA for lipid peroxidation. In addition, liver damage was evaluated histopathologically.
  
  
  RESULTS
  MTX significantly induced liver damage (P<0.05) and decreased its antioxidant capacity, while turmeric was hepatoprotective. Liver tissue microscopic evaluation showed that MTX treatment induced severe centrilobular and periportal degeneration, hyperemia of portal vein, increased artery inflammatory cells infiltration and necrosis, while all of histopathological changes were attenuated by turmeric (200 mg/kg).
  
  
  CONCLUSIONS
  Turmeric extract can successfully attenuate MTX-hepatotoxicity. The effect is partly mediated through extract's antinflammatory activity.
authors.affiliation: Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran. armoghadm@hotmail.com.
authors.forename: Adel Rezaei
authors.initials: AR
authors.lastname: Moghadam
authors.affiliation: Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran. soheyl_7@yahoo.com.
authors.forename: Soheil
authors.initials: S
authors.lastname: Tutunchi
authors.affiliation: Young Researchers and Elite club, Tabriz Branch, Islamic Azad University, Tabriz, Iran, Shiraz, Iran. dr.namvran@gmail.com.
authors.forename: Ali
authors.initials: A
authors.lastname: Namvaran-Abbas-Abad
authors.affiliation: Faculty of Veterinary Medicine, Tehran University, Tehran, Iran. Mina.Yazdi@gmail.com.
authors.forename: Mina
authors.initials: M
authors.lastname: Yazdi
authors.affiliation: Faculty of Medicine, Tehran Branch, Islamic Azad University, Tehran, Iran. f.bonyadi86@gmail.com.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Bonyadi
authors.affiliation: Department of Pathobiology, Tabriz Branch, Islamic Azad University, Islamic Azad University, Tabriz, Iran. daryoushmohajeri@yahoo.com.
authors.forename: Daryoush
authors.initials: D
authors.lastname: Mohajeri
authors.affiliation: Department of Biochemistry, Ardabil University of Medical Science, Ardabil, Iran. m.mazani@arums.ac.ir.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Mazani
authors.affiliation: Department of Human Anatomy and Cell Science, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada. hassan.marzban@med.umanitoba.ca.
authors.forename: Hassan
authors.initials: H
authors.lastname: Marzban
authors.affiliation: Department of Clinical and Experimental Medicine (IKE), Division of Cell Biology, and Integrative Regenerative Medicine Center (IGEN), Linköping University, Linköping, Sweden. marek.los@liu.se.|Department of Pathology, Pomeranian Medical University, Szczecin, Poland. marek.los@liu.se.|ENT Department, School of Medicine, Medical University of Silesia, Katowice, Poland. marek.los@liu.se.
authors.forename: Marek J
authors.initials: MJ
authors.lastname: Łos
authors.affiliation: Department of Human Anatomy and Cell Science, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada. saeid.Ghavami@gmail.com.|The Children Hospital Research Institute of Manitoba, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada. saeid.Ghavami@gmail.com.|Health Policy Research Centre, Shiraz Medical University, Shiraz, Iran. saeid.Ghavami@gmail.com.
authors.forename: Saeid
authors.initials: S
authors.lastname: Ghavami
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D030024:Curcuma; D008099:Liver / Q000187:drug effects*; D008297:Male; D008727:Methotrexate / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010936:Plant Extracts; D020011:Protective Agents; C012596:turmeric extract; D008727:Methotrexate