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

Abstract

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 p22phox 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)‑1α. 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‑1α 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.

Alterations in the gut barrier and involvement of Toll‐like receptor 4 in murine postoperative ileus

“…It includes claudin‐1 which is a pore‐sealing claudin. Its increase enhances epithelial tightness, whereas claudin‐2 is a pore‐forming protein whose increase results in decreased epithelial tightness and increased intestinal permeability . In this study, we found that claudin‐1 mRNA and protein levels were not significantly changed, whereas claudin‐2 was upregulated in POI mice.…”

Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3

“…Interestingly, our experiments also demonstrated a role for claudin 3 in regulating aspartame-induced oxidative stress in the intestinal epithelial cell. Previous in vivo studies have demonstrated a role for oxidative stress in the dysregulation of claudin 1, 2, and 4 expression at the tight junction due to reduced levels of the antioxidant and superoxide dismutase or increased levels of hypoxia-inducible factor-1 [ 49 , 50 ]. In addition, in gastric epithelial cells, claudin 3 was identified to be sensitive to oxidative stress, with the siRNA knockdown of the tight junction protein exacerbating the permeability of the monolayer [ 51 ].…”

Impact of Cigarette Smoking on the Gastrointestinal Tract Inflammation: Opposing Effects in Crohn’s Disease and Ulcerative Colitis

“…In addition, cigarette smoke has high levels of reactive oxygen species, peroxynitrite, peroxynitrate, free radicals, and reactive organic compounds that produce oxidative stress and modulate nitric oxide-dependent endothelial function ( 4 ). In fact, both smokers and animals exposed to cigarette smoke have markers of systemic oxidative stress ( 8 ), which can negatively affect susceptible tissues, such as the gastrointestinal tract.…”

“…Indeed, oxidative stress has been widely associated with CD, especially because enhanced oxidative stress and decreased antioxidant levels have been reported in patients with active CD ( 78 ). Interestingly, Li et al demonstrated that cigarette smoke exposure increases oxidative stress in the small intestine of rats, causing upregulation of the nicotinamide adenine dinucleotide phosphate oxidase, while the antioxidative enzyme superoxide dismutase was downregulated ( 8 ). Again, this deleterious effect seems to predominate in CD, due to the impact it would have on bacterial clearance, as explained below.…”