In this study, we have evaluated the effects of the
polyphenol epigallocatechin-3-gallate (EGCG), an
antioxidant molecule that also enhances constitutive
nitric-oxide synthase (NOS) activity, on
antigen-induced
asthma-like reaction in sensitized guinea pigs. For comparison, we used
epicatechin, which shares
antioxidant but not NOS-modulating properties with EGCG.
Ovalbumin-sensitized guinea pigs placed in a respiratory chamber were challenged with
ovalbumin. EGCG (25 mg/kg b.wt.) or
epicatechin (25 mg/kg b.wt.) was given i.p. 20 min before
ovalbumin challenge. We analyzed latency time for the onset of respiratory abnormalities,
cough severity, duration of
dyspnea, lung tissue histopathology, mast cell activation (by granule release), leukocyte/eosinophilic infiltration (by major basic
protein and
myeloperoxidase),
oxygen free radical-mediated injury (by
nitrotyrosine and
8-hydroxy-2-deoxyguanosine and
superoxide dismutase), NOS activity, and bronchial inflammatory response [by
tumor necrosis factor-alpha in bronchoalveolar lavage (BAL)]. In the sensitized animals, severe respiratory abnormalities appeared soon after the
antigen challenge, accompanied by bronchoconstriction, alveolar inflation, and a marked increase in the assayed parameters of inflammatory cell recruitment,
free radical lung injury, and release of proinflammatory molecules in BAL fluid. This was associated with marked depression of constitutive NOS activity. Pretreatment with EGCG, but not
epicatechin, significantly reduced all the above parameters and sustained endothelial-type NOS activity. These findings provide evidence that EGCG, probably by modulating NOS activity, can counteract allergic
asthma-like reaction in sensitized guinea pigs and suggest its possible future use for the treatment of
asthma.