Reactive oxygen species have been implicated in the pathogenesis of
asthma and, in atopic asthmatics, endogenous
superoxide dismutase (SOD)
enzyme levels are known to decrease. This suggests that replacing a failed endogenous SOD
enzyme system with a mimetic of the endogenous
enzyme would be beneficial and protective. In this study we demonstrate that removal of
superoxide by the SOD mimetic (SODm)
M40403 reduces the respiratory and histopathological lung abnormalities due to
ovalbumin (OA)
aerosol in a model of allergic
asthma-like reaction in sensitized guinea pigs. Both respiratory abnormalities and bronchoconstriction in response to OA challenge are nearly absent in naïve animals, while they sharply became severe in sensitized animals. In addition, OA
aerosol induced a reduction of MnSOD activity which was paralleled with bronchiolar lumen reduction, pulmonary air space hyperinflation, mast cell degranulation, eosinophil infiltration, bronchial epithelial cell apoptosis, increase in
myeloperoxidase activity,
malonyldialdehyde production and
8-hydroxy-2'-deoxyguanosine formation in the lung tissue, as well as elevation of
PGD2 in the bronchoalveolar lavage fluid. Treatment with
M40403 restored the levels of MnSOD activity and significantly reduced all the above parameters. In summary, our findings support the potential
therapeutic use of SOD mimetics in
asthma and
anaphylactic reactions and account for a critical role for
superoxide in acute allergic
asthma-like reaction in actively sensitized guinea pig.