title: Rivaroxaban Induces Mucosal Healing in a Rat Model of Trinitrobenzene Sulfonic Acid-Induced Colitis.
abstract: OBJECTIVE
  This study was designed to identify the effect of rivaroxaban, a direct factor Xa inhibitor, on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats.
  
  
  METHODS
  Twenty-four female Wistar rats were divided into 4 groups of 6 each. Group 1 received TNBS + rivaroxaban, group 2 received TNBS + methylprednisolone, group 3 received TNBS and group 4 received a saline enema. Colitis was induced in the rats by the intracolonic administration of TNBS. Rivaroxaban and methylprednisolone were given by oral gavage daily for 7 days. The rats were killed 7 days after the induction of colitis.
  
  
  RESULTS
  Rivaroxaban and methylprednisolone significantly reduced gross damage and histopathological scores. Rivaroxaban was more effective than methylprednisolone in terms of microscopic mucosal healing. Rivaroxaban attenuated the accumulation of malonyldialdehyde (MDA) and transforming growth-factor β1 (TGF-β1) and the activities of myeloperoxidase (MPO), matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1. Methylprednisolone reduced only the activity of MPO and the accumulation of MDA and TGF-β1. Superoxide dismutase activity showed a restoration to normal levels after rivaroxaban and methylprednisolone administration.
  
  
  CONCLUSIONS
  Rivaroxaban showed a therapeutic effect in the TNBS model of experimental colitis, and it seemed to be at least as effective as methylprednisolone. This effect may be brought about by the inhibition of oxidative stress and metalloproteinase activity associated with tissue injury and remodeling.
authors.affiliation: Department of Gastroenterology, Gazi University Medical School, Ankara, Turkey.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Gul Utku
authors.forename: Eylem
authors.initials: E
authors.lastname: Akbay Karatay
authors.forename: Harun
authors.initials: H
authors.lastname: Erdal
authors.forename: Mehmet
authors.initials: M
authors.lastname: Arhan
authors.forename: Ibrahim Koral
authors.initials: IK
authors.lastname: Onal
authors.forename: Mehmet
authors.initials: M
authors.lastname: Ibis
authors.forename: Ozgur
authors.initials: O
authors.lastname: Ekinci
authors.forename: Canan
authors.initials: C
authors.lastname: Yilmaz Demirtas
authors.forename: Selahattin
authors.initials: S
authors.lastname: Unal
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D065427:Factor Xa Inhibitors / Q000494:pharmacology*; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects*; D008315:Malondialdehyde / Q000378:metabolism; D008775:Methylprednisolone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000069552:Rivaroxaban / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid / Q000009:adverse effects; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D065427:Factor Xa Inhibitors; D007166:Immunosuppressive Agents; D053773:Transforming Growth Factor beta1; D008315:Malondialdehyde; D014302:Trinitrobenzenesulfonic Acid; D000069552:Rivaroxaban; D008775:Methylprednisolone