Rivaroxaban Induces Mucosal Healing in a Rat Model of Trinitrobenzene Sulfonic Acid-Induced Colitis

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. Materials and 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 activites 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.

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