title: The Impact of Resveratrol on Oxidative Stress Induced by Methotrexate in Rat Ileum Tissue: Evaluation of Biochemical and Histopathological Features and Analysis of Gene Expression.
abstract: OBJECTIVE
  The aim of this study was to assess the impact of resveratrol (RST) on oxidative stress induced by methotrexate in rat ileum tissue.
  
  
  METHODS
  Twenty-four rats were divided into 4 groups with 6 in each group. Each rat was orally administered the following every day for 30 days: group 1 (MTXG), methotrexate (MTX; 5 mg/kg); group 2 (RMTXG), MTX (5 mg/kg) plus RST (25 mg/kg/day); group 3 (RSTG), RST alone (25 mg/kg/day), and group 4 (controls), distilled water. After the rats had been sacrified, the ilea were removed for the assessment of malondialdehyde (MDA), total glutathione (tGSH) and glutathione peroxidase (GSH-Px). Gene expression analyses for interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) were also performed. Hematoxylin and eosin-stained paraffin-embedded sections of the ileum were analyzed under a light microscope and the findings were recorded. Statistical analyses of the data were performed using one-way ANOVA.
  
  
  RESULTS
  The administration of MTX in group 1 yielded a higher level of MDA (8.33 ± 2.5 μmol/g protein, p < 0.001) and lower levels of tGSH (0.97 ± 0.29 nmol/g protein) and GSH-Px (5.22 ± 0.35 U/g protein, p < 0.001) compared to the other groups. MTX also increased IL-1β (40.33 ± 5.43 gene expression levels), TNF-α (6.08 ± 0.59) and MPO gene expression (9 ± 1.41) in group 1 compared to the controls (11.33 ± 2.07, 2.15 ± 0.33 and 3.43 ± 0.48, respectively, p < 0.001). The impact of RST on IL-1β, TNF-α and MPO gene expression induced by MTX was observed as a reversal of these findings (p < 0.05). Severe inflammation, damage to the villus epithelium and crypt necrosis was observed histopathologically in the MTXG group, whereas only mild inflammation was seen in the RMTXG group.
  
  
  CONCLUSIONS
  In this study, ileal damage caused by MTX was inhibited by RST.
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Erzincan University, Erzincan, Turkey.
authors.forename: Adalet
authors.initials: A
authors.lastname: Ozcicek
authors.forename: Nihal
authors.initials: N
authors.lastname: Cetin
authors.forename: Ferda
authors.initials: F
authors.lastname: Keskin Cimen
authors.forename: Levent
authors.initials: L
authors.lastname: Tumkaya
authors.forename: Ismail
authors.initials: I
authors.lastname: Malkoc
authors.forename: Mine
authors.initials: M
authors.lastname: Gulaboglu
authors.forename: Oguzhan
authors.initials: O
authors.lastname: Yarali
authors.forename: Bahadir
authors.initials: B
authors.lastname: Suleyman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D005260:Female; D005979:Glutathione Peroxidase / Q000097:blood; D007077:Ileal Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D007082:Ileum / Q000187:drug effects* / Q000473:pathology; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D008727:Methotrexate / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000975:Antioxidants; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D005979:Glutathione Peroxidase; D008727:Methotrexate