Influence des donneurs de méthyle et du métabolisme de l'homocystéine dans la physiopatholie des MICI : Etudes de population et modèle expérimental chez le raton carencé

Abstract : Studies in populations from Central China and Lorraine showed a correlation between MTR, MTRR, MTHFR and hemorrhagic colitis and Crohn disease. In addition there was a correlation between MTRR and oxidative stress depending on superoxyde dismutase concentration and disease severity. Besides, Crohn disease was characterized by elevated homocysteine and decreased vitamin B12 linked to ileal resection and the effect of oxidative stress on MTRR capacity to reduce vitamin B12. On the other hand, in rats exposed to DSS, which is a potent inducer of inflammatory lesions in colonic mucosa, the extent of inflammation was aggravated by additional exposure to a diet deficient in methyl group donors. Unexpectedly, methyl group donor deficiency in rats did not yield any effect on apoptosis nor oxidative stress. However methyl group donor deficiency induced elevated expression of actors in the p38/cPLA2/COX2 pathway that leads to PGE2 production without affecting neither COX1 nor 5-LOX. These results uncover new pathophysiological events in inflammatory bowel disease (IBD). They depict intricated relationships in which the disease may cause malabsorption, and therefore a deficiency in methyl donors, oxidative stress decreases the capacity to reduce vitamin B12 in the digestive epithelium and methyl group donors deficiency exacerbates inflammatory mechanisms triggered by exposure to exogenous agents such as bacteria.
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Min Chen. Influence des donneurs de méthyle et du métabolisme de l'homocystéine dans la physiopatholie des MICI : Etudes de population et modèle expérimental chez le raton carencé. Sciences agricoles. Université Henri Poincaré - Nancy 1, 2009. Français. ⟨NNT : 2009NAN10044⟩. ⟨tel-01748502⟩

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