Metabolomic analysis of the effect of endocannabinoid metabolism inhibition in allergic airway inflammation

<bold>Background:</bold> Asthma manifests as a multifaceted airway inflammation. The therapeutic potential of targeting endocannabinoids (ECs) in mitigating asthma remains incompletely elucidated. <bold>Aims:</bold> To scrutinize metabolic alterations, deepen our comprehension of the ECs' therapeutic role, and discern novel biomarkers for monitoring allergic airway inflammation. <bold>Methods:</bold> Guinea pigs were sensitized with ovalbumin (150μg) or PBS on days 1, 4, and 7. On day 14, they were exposed to aerosols containing 0.3%ovalbumin or PBS. Treatment groups were administered inhibitors of fatty acid amide hydrolase (FAAH) and/or monoacylglycerol lipase (MAGL) one hour prior to aerosol exposure (Abohalaka et al. Life sciences 2022;306:12080). Subsequently, bronchoalveolar lavage (BAL), blood, and lung samples were collected on the following day for analysis using GC-MS (Abohalaka et al. Biomedical Chromatography 2022;36(1):e5231). <bold>Results:</bold> Ovalbumin exposure altered the metabolic profile in the lung. Conversely, inhibition of ECs metabolism induced a systemic shift in energy metabolites such as carbohydrates, amino and fatty acids (Figure 1). <bold>Conclusions:</bold> Allergen exposure induced an elevation in metabolites associated with glycolytic metabolism particularly in the lungs, indicating enhanced activation and increased numbers of immune cells. Notably, inhibition of ECs mitigated these shifts, underscoring its anti-inflammatory efficacy. <fig><object-id>erj;64/suppl_68/PA2989/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>