Acute glutathione depletion underlies the early asthmatic response in a guinea pig model of allergic asthma

Substantial evidence suggests that oxidative stress in the lungs can affect the pathological events observed in asthma. We used a guinea pig model of asthma to assess whether the early asthmatic reaction is associated with decreased lung levels of glutathione, and whether a decrease in glutathione is implicated in the increased airway smooth muscle reactivity that is associated with exposure of the lungs to allergen. Lung glutathione levels were decreased immediately after the onset of the early asthmatic reaction in vivo. Glutathione-ethyl ester, a glutathione precursor, blunted the airway obstruction during an early asthmatic reaction in a perfusion model and glutathione depletion rendered the airways hyperreactive. Glutathione ethyl ester in the buffer prevented this hyperreactivity. These results indicate that glutathione modulates airway responsiveness in the early asthmatic reaction. Early asthmatic response and glutathione depletion | 49