Supplementation of antioxidants glutathione and α-lipoic acid attenuates oxidative stress and Th2 response in allergic airway inflammation

Abstract

Background: Inflammatory lung diseases such as asthma are characterized by chronic inflammation, oxidative stress, and altered antioxidant defenses. Increased levels of reactive oxygen species (ROS) contribute to asthma exacerbation and cell damage. Exogenous supplementation of antioxidant combinations has shown potential in asthma management. Previously, a hypoallergenic mutated glutathione S-transferase (mGST) singly or in combination with reduced glutathione (GSH) showed reduction in airway inflammation in mice model. Objective: The present study evaluates the effects of antioxidants α-lipoic acid and α-tocopherol in combination with mGST or GSH in neutralizing the oxidative stress and reducing the inflammatory responses in a mouse model. Materials and Methods: BALB/c mice were immunized and challenged with ovalbumin, treated with different antioxidant combinations by inhalation, and sacrificed to evaluate inflammation and oxidative stress parameters. Result: Treatment with GSH + α-lipoic acid showed significantly reduced total cell and eosinophil counts in bronchoalveolar lavage fluid (BALF) and decreased infiltration of cells into lung interstitium, compared to ovalbumin group. Also, the treatment reduced interleukin (IL)-4 and ovalbumin-specific IgE levels possibly through modulation of redox-sensitive transcription factor nuclear factor-kappa B (NF-κB) levels. Administration of all antioxidant combinations decreased the ROS compared to ovalbumin group as indicated by reduced thiobarbituric acid reactive substance (TBARS) and 8-isoprostane levels in BALF. Conclusion: All antioxidant combinations of α-lipoic acid and α-tocopherol in combination with mGST or GSH showed reduction in airway inflammation and oxidative stress in vivo, but maximum therapeutic efficacy was observed in GSH + α-lipoic acid group. Therefore, a combination of antioxidants may prevent allergic inflammation in the best possible way.