Ebselen prevents cigarette smoke-induced gastrointestinal dysfunction in mice

Area of Science:

• Gastroenterology
• Pulmonology
• Toxicology

Background:

• Gastrointestinal (GI) dysfunction is a frequent comorbidity in chronic obstructive pulmonary disease (COPD).
• Cigarette smoking (CS) is a primary cause of COPD and associated GI issues, yet mechanisms remain unclear.
• Investigating CS effects on gut function is crucial for understanding COPD comorbidities.

Purpose of the Study:

• To investigate the impact of CS on GI function and structure in a mouse model of CS-induced COPD.
• To explore the therapeutic potential of ebselen, an antioxidant, in mitigating CS-induced GI changes.
• To characterize changes in colonic motility and neuronal structure following short-term and long-term CS exposure.

Main Methods:

• Mice were exposed to CS for 2 or 6 months.
• GI structure analyzed via histology and immunofluorescence.
• Ex vivo colonic motility assessed using video imaging to measure colonic migrating motor complexes (CMMCs) and colonic diameter.

Main Results:

• CS exposure reduced colon length and resting colonic diameter after 2 months.
• CMMC frequency increased after 2 months of CS, reversing upon cessation, while diameter changes persisted.
• Ebselen treatment reversed CS-induced reductions in colonic diameter.
• Prolonged CS exposure (6 months) significantly reduced myenteric nitric-oxide producing neurons.

Conclusions:

• This study provides the first evidence of colonic dysmotility in a mouse model of CS-induced COPD.
• Early GI dysmotility is not neuron-number dependent but is influenced by prolonged CS exposure.
• Ebselen shows promise in reversing CS-induced colonic diameter changes, warranting further investigation for therapeutic applications in COPD-related GI dysfunction.