A metabonomic approach to evaluate COPD in a model of cigarette smoke exposure in mice

This study aims to develop an NMR-based metabonomic approach to diagnostic evaluation of Chronic Obstructive Pulmonary Disease (COPD) in a model of smoke exposure in mice. The current study compared the effects of acute and chronic smoke exposures performed on three strains of mice susceptible to develop COPD and two strains resistant to this disease. Intact lung tissue was examined using high-resolution magic angle spinning (HR-MAS). Six chemical shifts of the H-1 NMR spectrum including taurine, glutathione, phosphoryl choline and glycero-phosphocholine, were selected to ensure a high discrimination between control and acute exposed mice in the susceptible strain and, simultaneously, a low discrimination in the resistant strains. Using these metabolites, a chronic predictive model was developed and validated. The multivariate analysis provides a 100% true classification for sick mice and 78% for control animals. This pioneering study demonstrates that the NMR-based metabonomic analysis of intact lung tissue is a potential technique for the detection of COPD biomarkers and for the diagnosis of COPD in a mouse model of COPD. It might boost the study of tobacco smoke effects on other non- or less-invasive samples.