Protection is supplied by complex mechanisms which support one another: intestinal secretions (primarily mucus and secretory IgA), the mucosal epithelium, and intramural lymphocytes .
This primary, intestinal barrier is supported by the liver, through which all enterically-derived substances must pass before entering the arterial circulation for transport to other tissues and organs.
Single doses of aspirin or of indomethacin increase -cellular permeability, in part by inhibiting the synthesis of protective prostaglandins [20, 49, 50, 84, 85].
We designed and synthesized conformationally restricted analogues and regioisomers of the nonsteroidal anti-inflammatory drug indomethacin. Evaluation of the inhibitory effects of these compounds on COX, P-glycoprotein, and multidrug resistance indicated that NSAIDS modulation of multidrug-resistant P-glycoprotein and multidrug-resistant protein-1 is not associated with COX-1 and COX-2 inhibitory activities.
T1 - Design and synthesis of indomethacin analogues that inhibit P-glycoprotein and/or multidrug resistant protein without Cox inhibitory activity
Direct measurement of intestinal permeability allows the clinician to plan appropriate strategies and to gauge the effectiveness of treatment, using objective parameters.
At high levels of supplementation, they produce hyperpermeability, probably by inducing synthesis of bacterial enzymes which degrade intestinal mucins[148-151].
In experimental animals, fish oil feeding ameliorates the intestinal mucosal injury produced by methotrexate and, additionally, blunts the systemic circulatory response to endotoxin.
Patients with intestinal mucosal injury secondary to chemotherapy or radiation benefit from glutamine supplementation with less villous atrophy, increased mucosal healing and decreased passage of endotoxin through the gut wall[140-143].
Patients and experimental animals that are fasted or fed only by a parenteral route develop intestinal villous atrophy, depletion of SIgA, and translocation of bacteria from the gut lumen to the systemic circulation.
Avoidance of enterotoxic drugs, treatment of intestinal infection or dysbiosis, and an allergy elimination diet of high nutrient density that is appropriate for the individual patient are the primary treatment strategies for the Leaky Gut Syndromes.
Basic vitamin and mineral supplementation should include all the B vitamins, retinol, ascorbate, tocopherol, zinc, selenium, molybdenum, manganese, and magnesium.
Dietary supplementation with betaine hydrochloride is usually helpful but intermittent short courses of bismuth, citrus seed extract, artemisinin, colloidal silver and other natural antimicrobials are often needed.
In the absence of intestinal surgery, strictures or fistulae, bacterial overgrowth is most likely a sign of hypochlorhydria resulting from chronic gastritis due to infection.
NSAIDs like indomethacin, which undergo enteroheaptic recirculation, are more likely to damage the small intestine that NSAIDs that are not excreted in bile, like ibuprofen .
For maximum benefit with regard to intestinal permeability, dietary fibre supplementation should therefore contain a predominance of hypoallergenic insoluble fibre.