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P024. Jejunal glucose absorption is decreased in rat models of colitis through extrinsic neuronal mechanisms

F.H. Mourad, K.A. Barada, D. Bou Matar, N.E. Saade

American University of Beirut, Beirut, Lebanon

Background and Aims: A significant decrease in jejunal fluid, amino acid and fat absorption has been described in patients with inflammatory bowel disease and in models of experimental colitis. The pathophysiology of this dysfunction has not been elucidated. Our aim is to study the effect of experimental colitis on jejunal glucose absorption and to determine the role of the extrinsic innervation, and the possible involvement of neuronal and inducible NO in this process.

Methods: Two established rat models of acute and chronic colitis induced by iodoacetamide (IA) and trinitrobenzenesulphonic acid (TNBS), respectively, were used. Jejunal glucose absorption was evaluated by the in-vivo single pass perfusion technique at different time intervals after colitis induction. The effects of (i) the peripheral adrenergic blocking agent guanethidine, (ii) the nicotinic receptor antagonist hexamethonium, (iii) the neuronal nitric oxide synthase (NOS) inhibitor L-nitroindazole, (iv) the inducible NOS inhibitor aminoguanidine, and v) those of ablation of capsaicin sensitive primary afferent (CSPA) fibres were studied.

Results: Basal jejunal glucose absorption (13.9±0.5 μmol×h−1×cm−1) significantly decreased at 2 days post IA (8.5±0.4; p < 0.001), and at 7 and 21 days following TNBS treatment (7.5±0.2 and 10.9±0.2, respectively; p < 0.001). Guanethidine totally prevented this drop in glucose absorption in both models (IA: 12.8±0.5 at 2 days, p < 0.001; TNBS: 11.1±0.7 and 14.8±0.7 at 7 and 21 days, respectively; both p < 0.01). Hexamethonium had an effect similar to that of guanethidine (IA: 12.3±1 at 2 days, p < 0.01; TNBS: 14.0±0.6 and 13.9±0.5 at 7 and 21 days, respectively; both p < 0.001). Guanethidine and hexamethonium had no effect on basal glucose absorption in controls. Nitroindazole and aminoguanidine partially prevented the IA-induced inhibition of glucose absorption (10.1±0.5; p < 0.01 and 12.0±0.5; p < 0.05, respectively) although they both decreased basal glucose absorption. CSPA fibres ablation significantly decreased basal jejunal glucose absorption (8.91±0.6; p < 0.01) but no further drop was observed after induction of colitis.

Conclusion: Chemical colitis is associated with a significant decrease in jejunal glucose absorption. This decrease is mediated, at least partially by sympathetic intestinal efferents innervation and involves NO-related mechanisms.