Glutathione peroxidase activity in blood cells from aspirin-induced asthma patients

Abstract

Aspirin and other inhibitors of cyclo-oxygenase precipitate acute bronchospasm in about 10% of adult asthmatics. It has been assumed that cyclo-oxygenase is involved in the pathogenesis of bronchospasm, but the precise mechanism remains poorly understood. The oxygenation products of arachidonic acid include hydroperoxyeicosatetraenoic acid and cyclic endoperoxides. Glutathione peroxidase (GPX) reduces semi-stable hydroperoxides to less reactive alcohols and removes H(2)O(2) involved in inflammation. GPX could, therefore, modulate oxidation of arachidonic acid in the cyclo-oxygenase and lipoxygenase pathways, but the involvement of GPX in the pathogenesis of asthma has received little attention. We measured GPX activity in platelets, peripheral blood lymphocytes (PBL), red blood cells (RBC) and plasma from 13 patients with aspirin-induced asthma (AIA). Age- and sex-matched healthy individuals served as the comparison group. The patients had significantly higher GPX activity in platelets (P = 0.05) and tended to have high GPX activity (P = 0.08) in plasma but not in RBC or PBL. The results suggest that the increased GPX activity may be an adaptive advantage in AIA to protect against increased free radical production by inflammatory cells. That the higher GPX activity was not evident in all cell types studied may indicate a differential role played by them as effector cells in the pathogenesis of AIA.

Application of an Integrative Drug Safety Model for Detection of Adverse Drug Events Associated With Inhibition of Glutathione Peroxidase 1 in Chronic Obstructive Pulmonary Disease

“…In the FAERS analysis, dyspnoea seems to be reported more frequently for acetylsalicylic acid compared to other drugs (ROR 1.05 95% CI 1.02–1.07). Its use is also associated with acute bronchospasm in approximately 10% of people diagnosed with asthma [ 65 , 66 ]. Moreover, GPx activity has been shown to be significantly compromised in the red blood cells of patients with acetylsalicylic acid-induced asthma compared to control patients [ 65 ].…”

“…Its use is also associated with acute bronchospasm in approximately 10% of people diagnosed with asthma [ 65 , 66 ]. Moreover, GPx activity has been shown to be significantly compromised in the red blood cells of patients with acetylsalicylic acid-induced asthma compared to control patients [ 65 ]. Further analyses are required to determine whether acetylsalicylic acid alters GPx1 function in vitro at either antiplatelet or analgesic doses.…”