title: Effect of mesalamine and prednisolone on TNBS experimental colitis, following various doses of orally administered iron.
abstract: BACKGROUND
  Experimental data suggest that oral iron (I.) supplementation can worsen colitis in animals.
  
  
  OBJECTIVE
  To investigate the influence of various concentrations of orally administered I. in normal gut mucosa and mucosa of animals with TNBS colitis, as well as the influence of Mesalamine (M.) and Prednisolone (P.) on the severity of TNBS colitis following orally administered I.
  
  
  METHODS
  156 Wistar rats were allocated into 10 groups. Colitis was induced by TNBS. On the 8th day, all animals were euthanatized. Activity of colitis and extent of tissue damage were assessed histologically. The levels of tissue tumor necrosis factor- α (t-TNF- α ) and tissue malondialdehyde (t-MDA) were estimated in all animal groups.
  
  
  RESULTS
  Moderate and high I. supplementation induced inflammation in the healthy colon and increased the activity of the experimentally induced TNBS colitis. Administration of M. on TNBS colitis following moderate iron supplementation (0.3 g/Kg diet) resulted in a significant improvement in the overall histological score as well as in two individual histological parameters. M. administration, however, did not significantly reduce the t-TNF- α levels (17.67 ± 4.92 versus 14.58 ± 5.71, P = 0.102), although it significantly reduced the t-MDA levels (5.79 ± 1.55 versus 3.67 ± 1.39, P = 0.000). Administration of M. on TNBS colitis following high iron supplementation (3.0 g/Kg diet) did not improve the overall histological score and the individual histological parameters, neither reduced the levels of t-TNF- α (16.57 ± 5.61 versus 14.65 ± 3.88, P = 0.296). However, M. significantly reduced the t-MDA levels (5.99 ± 1.37 versus 4.04 ± 1.41, P = 0.000). Administration of P. on TNBS colitis after moderate iron supplementation resulted in a significant improvement in the overall histological score as well as in three individual histological parameters. P. also resulted in a significant reduction in the t-TNF- α levels (17.67 ± 4.92 versus 12.64 ± 3.97, P = 0.003) and the t-MDA levels (5.79 ± 1.54 versus 3.47 ± 1.21, P = 0.001). Administration of P on TNBS colitis after high I. supplementation resulted in a significant improvement of the overall histological score and three individual histological parameters and significantly reduced the levels of t-TNF- α (16.6 ± 5.6 versus 11.85 ± 1.3, P = 0.001).
  
  
  CONCLUSIONS
  I. can induce colonic inflammation and aggravate TNBS colitis. M. and P. can significantly improve the inflammatory process in the colonic mucosa in TNBS colitis aggravated by orally administered I. P. has a stable anti-TNF- α effect. These findings suggest that the harmful.
authors.affiliation: Inflammatory Bowel Disease Unit, IASO General Hospital, 264 Mesogeion Avenue, Holargos, 15562 Athens, Greece.
authors.forename: John K
authors.initials: JK
authors.lastname: Triantafillidis
authors.affiliation: Inflammatory Bowel Disease Unit, IASO General Hospital, 264 Mesogeion Avenue, Holargos, 15562 Athens, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Douvi
authors.affiliation: 1st Department of Pathology, University of Athens, School of Medicine, 75 Mikras Asias, 115 27 Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Agrogiannis
authors.affiliation: 1st Department of Pathology, University of Athens, School of Medicine, 75 Mikras Asias, 115 27 Athens, Greece.
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.affiliation: Health Center of Kalivia, Attiki, 1st Klm Kalivion Avenue, 19010 Kalivia, Greece.
authors.forename: Aristofanis
authors.initials: A
authors.lastname: Gikas
authors.affiliation: Experimental and Research Center, ELPEN Pharma, 95 Marathonos Avenue, Pikermi, 19009 Athens, Greece.
authors.forename: Apostolos E
authors.initials: AE
authors.lastname: Papalois
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003092:Colitis / Q000188:drug therapy* / Q000473:pathology; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007501:Iron / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D019804:Mesalamine / Q000494:pharmacology / Q000627:therapeutic use*; D011239:Prednisolone / Q000494:pharmacology / Q000627:therapeutic use*; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D019804:Mesalamine; D008315:Malondialdehyde; D014302:Trinitrobenzenesulfonic Acid; D011239:Prednisolone; D007501:Iron