Ebselen prevents cigarette smoke-induced gastrointestinal dysfunction in mice

Abstract

Gastrointestinal (GI) dysfunction is a common comorbidity of Chronic Obstructive Pulmonary Disease (COPD) for which a major cause is cigarette smoking (CS). The underlying mechanisms and precise effects of CS on gut contractility, are not fully characterised. Therefore, this study aimed to investigate whether CS impacts GI function and structure in a mouse model of CS-induced COPD. We also aimed to investigate GI function in the presence of ebselen, an antioxidant that has shown beneficial effects on lung inflammation resulting from CS exposure. Mice were exposed to CS for 2 or 6 months. GI structure was analysed by histology and immunofluorescence. After 2-months of CS exposure, ex vivo gut motility was analysed using video-imaging techniques to examine changes in colonic migrating motor complexes (CMMCs). CS decreased colon length in mice. Mice exposed to CS for 2 months had a higher frequency of CMMCs and a reduced resting colonic diameter but no change in enteric neuron numbers. 10-days cessation after 2 months CS reversed CMMC frequency changes but not the reduced colonic diameter phenotype. Ebselen treatment reversed CS-induced reduction in colonic diameter. After 6 months CS, the number of myenteric nitric-oxide producing neurons was significantly reduced. This is the first evidence of colonic dysmotility in a mouse model of CS-induced COPD. Dysmotility after 2 months CS is not due to altered neuron numbers, however, prolonged CS-exposure significantly reduced enteric neuron numbers in mice. Further research is needed to assess potential therapeutic applications of ebselen in GI dysfunction in COPD.

The Bidirectional Gut–Lung Axis in Chronic Obstructive Pulmonary Disease

“…Moreover, exposure to cigarette smoke for 2 months caused decreased colonic diameter and an increased frequency of colonic contractions in male Balb/c mice; it is possible that nicotine contributed to these changes in gut function by acting on enteric neurons expressing nAChR to contract intestinal smooth muscle (95).…”

“…Antioxidants might have therapeutical potentials in gastrointestinal dysfunction in patients with COPD. The antioxidant ebselen prevents the reduction in colonic diameter in mice exposed to cigarette smoke for 2 months (95).…”

Chronic Exposure to Cigarette Smoke Affects the Ileum and Colon of Guinea Pigs Differently. Relaxin (RLX-2, Serelaxin) Prevents Most Local Damage

“…Indeed, although changes in gut motility are present in smokers and, mostly, in people affected by IBDs, this topic is very little investigated. In this regard, an interesting experimental paper has been recently published ( Balasuriya et al, 2020 ). In perspective, we could apply our methodology to investigate whether RLX-2 is able to prevent the increase in cell infiltrates consisting of eosinophils and the decrease in SP and VIP expressions reported in the colon of animal models ( Traini et al, 2017 ; Traini et al, 2021 ) that mimic the most common intestinal morpho-functional disease, irritable bowel syndrome.…”

Sigara İçiminin Gastrik Miyoelektrik Aktiviteye Etkisinin Araştırılması

“…İnsanlarda 2 -4 cpm dir. Yavaş dalga frekansı < 2cpm ise bradigastri, > 4cpm ise taşigastri ve spektrumda baskın bir pik gücü yoksa aritmi olarak isimlendirilir 1 [3][4][5] . Son zamanlarda mide-barsak motilite bozukluğunun birçok gastrointestinal hastalığın patogenezinde önemli rol oynayabileceği ve hastalığın iyileşme sürecini geciktirebileceği belirtilmiştir 6 .…”