Neonatal hyperoxia disrupts the intestinal barrier and impairs intestinal function in rats

Animal studies have demonstrated that neonatal hyperoxia injures the distal small intestine and disrupts the intestinal barrier. This study evaluated the effects of brief hyperoxia exposure on intestinal function in newborn rats. Newborn Sprague–Dawley rat pups were exposed to room air or normobaric hyperoxia (85% O2) for 1 week. The rats were euthanized on Postnatal Day 7, and their terminal ilea and sera were collected for histological analyses and intestinal permeability measurements, respectively. Bacterial translocation to the liver and spleen under aerobic and anaerobic conditions was determined. The expression and localization of epithelial injury markers [intestinal fatty acid binding protein (I-FABP)], intestinal barrier proteins [occludin and zonula occludens (ZO)-1], and inflammation biomarkers [Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB)] were analyzed through immunofluorescence staining. The body weight at birth was comparable between the two groups. On Postnatal Day 7, the rats in the hyperoxic group exhibited significantly lower body weights, higher intestinal injury scores, lower numbers of goblet cells, higher I-FABP expression, lower occludin and ZO-1 expression, higher TLR4 and NF-κB expression, and higher intestinal permeability and bacterial translocation than did those in the room air group. The rats reared in O2-enriched air displayed indistinct tight junction with widening of the paracellular spaces. Hyperoxia exposure injured the distal small intestine, disrupted the intestinal barrier, and impaired intestinal function in newborn rats. Hyperoxia-induced intestinal injury may be attributable to increased activity of the TLR4/NF-κB pathway during the postnatal period.