DEVELOPMENT OF ISCHEMIA REPERFUSION TOLERANCE IN THE RAT SMALL-INTESTINE - AN EPITHELIUM-INDEPENDENT EVENT/

In stable organ systems, such as the heart and kidneys, an oxidant str ess induces an increase in endogenous antioxidant systems resulting in an increased resistance of the tissue to a subsequent oxidant challen ge. The development of this oxidant tolerance requires 1.5-6 d. The ai m of the present study was to determine whether oxidant tolerance can be induced in the small intestinal mucosa, a labile system whose epith elium turns over every 2-3 d. Ischemia/reperfusion-induced epithelial barrier dysfunction of the small intestinal mucosa was monitored in Sp rague-Dawley rats whose intestines had been exposed to an ischemic ins ult 1, 24, or 72 h previously. At 24 h, but not 1 or 72 h after the in itial ischemic insult, the mucosa was more resistant to ischemia/ repe rfusion-induced barrier dysfunction. The antioxidant status of the muc osa was enhanced at 24 h, but not at 1 or 72 h after the initial ische mic insult. This adaptation appears to be specific for oxidants, since an initial ischemic insult imposed 24 h earlier also protected agains t H2O2-induced, but not acid- or ethanol-induced, barrier dysfunction. Further studies indicated that the increase in antioxidant status of the mucosa observed 24 h after the initial ischemic insult was a resul t of adaptational changes in the lamina propria, rather than the epith elium. In vitro studies with isolated epithelial cells also indicated that epithelial cells do not develop oxidant tolerance, We conclude th at the development of oxidant tolerance in the small intestinal mucosa does not involve an active participation of the epithelial lining.