Dietary Long Chain Triglycerides Protect Against Oral Sensitization to Peanut Protein and Promote Oral Tolerance in Mice in a Chylomicron-Dependent Manner

Abstract

induced intestinal lesions were examined in rats. The role of intestinal motility, capsaicinsensitive sensory neurons (CSSNs) and nitric oxide (NO) in the effects of the drugs was also examined. METHODS: Male Wistar rats were treated with IND (10 mg/kg, p.o.) after a 16 h-fast (for gastric ulcers) or without fasting (for intestinal ulcers). The animals were autopsied 24 h after IND administration, and the stomach and small intestine were examined for lesions. Intestinal motility was measured using a balloon method in anesthetized rats. RESULTS: 1. Gastric lesions: IND produced many linear lesions in the corpus mucosa, and the lesion index (LI, total length) in the vehicle-treated group was 25.6±5.3 mm (n=7). The LI was significantly (P<0.05) decreased by pretreatment with oral doses (mg/kg) of CIM (100), RAN (30), FAM (10), OPZ (30), LPZ (30) and RPZ (30). 2. Small intestinal lesions: IND produced many lesions in the middle and lower parts of the small intestine. The LI in the vehicle-treated group was 57.0±10.0 mm (n=10). (a) Effects of H2-RAs: CIM, RAN and FAM increased the LI by 94% (P<0.01), 82% (P<0.01), and 68% (P<0.05), respectively. H2-RAs (3-30, i.v.) did not directly affect intestinal motility, but they did increase the motility induced by IND (10, s.c.). (b) Effects of PPIs: OPZ (100) and RPZ (100) significantly (P<0.05) increased the LI by 48% and 33%, respectively, whereas LPZ (30) significantly (P<0.01) decreased the LI by 61%. The inhibitory effect of LPZ was abolished by functional ablation of CSSNs (20, 30 and 50 mg/kg of capsaicin was administered s.c. for 3 consecutive days 2 weeks before the experiment) or pretreatment with L-NAME (a NO synthase inhibitor). CONCLUSIONS: Though H2-RAs and PPIs markedly inhibited the formation of gastric lesions induced by IND, they (except for LPZ) increased the formation of small intestinal lesions. The results suggest that antisecretory drugs aggravate intestinal lesions induced by NSAIDs, probably by increasing the amount of indigestive foods in the intestine and by increasing intestinal motility. LPZ, though having a potent antisecretory action, inhibited the formation of intestinal lesions, and this action can be explained by its protective action on the mucosa via CSSNs and NO.