Metabolomic analysis of the effect of endocannabinoid metabolism inhibition in ovalbumin-induced allergic airway inflammation in Guinea pigs

Abstract

Background and aims: Asthma manifests as a multifaceted airway inflammation. The therapeutic potential of targeting endocannabinoids in mitigating asthma remains incompletely elucidated. Therefore, we aim to scrutinize metabolic alterations, deepen our comprehension of the endocannabinoids therapeutic role, and discern novel biomarkers for monitoring allergic airway inflammation. Methods: Guinea pigs were sensitized with ovalbumin (150 ug) 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. Subsequently, bronchoalveolar lavage (BAL), blood, and lung samples were collected on the following day for analysis using GC-MS. Metabolites were meticulously categorized into 10 distinct classifications based on their chemical and biological functions. Subsequently, they were further organized into 5 principal metabolic pathways for a comprehensive metabolomic analysis. Results: Ovalbumin exposure exclusively altered the metabolic profile in the lung. Conversely, inhibition of endocannabinoids metabolism induced a systemic shift in energy metabolites such as carbohydrates, amino and fatty acids. Conclusions: 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 endocannabinoids mitigated these shifts, underscoring its anti-inflammatory efficacy.