Search in the Abstract Database

Search Abstracts 2011

* = Presenting author

P012. Intrarectal administration of oxygenated perfluorodecalin promotes healing of murine colitis by targeting inflammatory hypoxia

P. Hindryckx, L. Devisscher, D. Laukens, H. Peeters, M. De Vos

Ghent University Hospital, Ghent, Belgium

Objective: Intestinal inflammation is associated with enhanced mucosal hypoxia, which contributes to the ongoing inflammatory process and hampers appropriate mucosal healing. We questioned whether local treatment with an oxygen-carrying and -releasing molecule (oxygenated perfluorodecalin, O2-PFD) could positively influence the course of experimental colitis.

Design: The impact of intrarectal treatment with O2-PFD was tested using the murine dextran sodium sulfate (DSS)-induced model of distal colitis, both in preventive and therapeutic settings. Colonic mucosal hypoxia was visualized by pimonidazole-staining. Colonic permeability was evaluated with FITC-dextran.

Results: In the preventive study, mice treated with O2-PFD were protected against DSS colitis compared to saline-treated mice, as demonstrated by reduced shortening of colon length, reduced colonic TNF-α levels and a lower histological inflammation score (P < 0.05 for all parameters). In the therapeutic study, administration of O2-PFD resulted in accelerated recovery of colitis compared to saline-treated littermates, and this was reflected by a better weight evolution, lower myeloperoxidase activity and a lower histological inflammation score (P < 0.05 for all parameters).

It was found that O2-PFD established its therapeutic effects through (i) intrinsic anti-inflammatory effects of the PFD molecule and (ii) O2-induced preservation and healing of the intestinal epithelial surface. Further in vitro and in vivo studies showed that the barrier-protective activity of O2-PFD was obtained through prevention of colonocyte apoptosis and stimulation of colonocyte proliferation during inflammatory hypoxia.

Conclusions: These data show that intrarectal treatment with oxygenated PFD promotes colitis healing by the combined actions of direct anti-inflammatory effects and O2-induced restitution of the epithelial barrier. As such, O2-PFD enemas could be an attractive treatment option for patients with distal IBD.