Increased oxidative stress and disrupted small intestinal tight junctions in cigarette smoke-exposed rats.

Chronic obstructive pulmonary disease (COPD) is a major public health problem, and cigarette smoke (CS) is the primary risk factor. The pathology is often observed in the lung, but COPD is also associated with intestinal barrier disruption, although the underlying mechanisms are poorly understood. To address this, a CS-exposed rat model was evaluated in the present study by analyzing small intestinal gene expression using reverse transcription-quantitative polymerase chain reaction. CS exposure caused upregulation of the nicotinamide adenine dinucleotide phosphate-oxidase subunits nox2 and p22(phox) in the small intestine, while the antioxidative enzyme superoxide dismutase was downregulated. CS exposure also increased bax expression and decreased bcl-2 expression. This was associated with an elevation of hypoxia-inducible factor (HIF)-1 alpha. Claudin-1 was decreased and claudin-2 increased, indicating a loosening of small intestinal tight junctions (TJs). These data suggest that during the development of COPD, HIF-1 alpha expression is altered in the small intestine, which may be associated with the increased oxidative stress and apoptosis, eventually resulting in disruption of the intestinal TJs.