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* = Presenting author

P009. Treatment of intestinal fibrosis with tocotrienols in an optimized rat model

J. Luna1, R. Mora1, M. Masamunt1, T. Nunes1, J. Llach1, S. Delgado1, X. Molero2, E. Vaquero1, M. Sans1

1IDIBAPS, Barcelona, Spain; 2Hospital Vall d'Hebron, Barcelona, Spain

Background: Tocotrienols have potent antifibrogenic effects in vitro on human intestinal fibroblasts. The aim of this study was to evaluate the usefulness of tocotrienols to prevent the development of intestinal fibrosis in an optimized rat model.

Methods: Sprague-Dawley rats were treated with several regimes of intrarectal TNBS. Once the optimal model was established, animals were treated with oral administration of 10, 50 or 150 μl/day of tocotrienol rich fraction (TRF) from palm oil, started 10 days prior to the first TNBS dose and continued for 3 weeks after the first TNBS dose. At this point animals were sacrificed and intestinal fibrosis was quantified in colonic preparations stained with Mason's trichromic, by means of a computer-assisted morphometric analysis. Colonic expression of collagen I and III, TNF-α and vimentin was measured by RT-PCR and TGF-β1 activation and MMP-3 and TIMP-1 production by Western-blot.

Results: Treatment with 10 mg/week of TNBS for 3 weeks was the best regime to induce intestinal fibrosis. After 1 week marked submucosal enlargement was due to inflammatory infiltrate and edema, which was substituted by fibrotic tissue at 3 weeks. None of the TRF doses was able to reduce the fibrotic tissue area. However, treatment with 150 μl of TRF significantly (p < 0.05) reduced diarrhea, rectal bleeding and animal weight loss, as well as colonic TNF-α and vimentin expression.

Conclusions: TRF did not prevent intestinal fibrosis in an optimized rat model. However, treatment with TRF had anti-inflammatory effects, decreasing some of the clinical hallmarks of TNBS-induced colitis. We therefore can't rule out the possibility that treatment with TRF for longer periods of time might improve intestinal fibrosis.