Received for publication February 2, 2006.
Revised March 7, 2006.
Accepted for publication March 7, 2006.

EPIGALLOCATECHINE-3-GALLATE REDUCES ALLERGEN-INDUCED ASTHMA-LIKE REACTION IN SENSITISED GUINEA PIGS

Abstract

In this study we have evaluated the effects of the polyphenol epigallocatechine-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 epicatechine, which shares antioxidant but not NOS-modulating properties with EGCG. Ovalbumin-sensitized guinea pigs placed in a respiratory chambers were challenged with ovalbumin. EGCG (25 mg/kg b.wt.) or epicatechine (25 mg/kg b.wt.) were given i.p. 20 min. before ovalbumin challenge. We analysed: 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, eMBP, and myeloperoxidase); oxygen free radical-mediated injury (by nitrotyrosine and 8-hydroxy-2-deoxyguanosine, 8OHdG, and superoxide dismutase, SOD); NOS activity; bronchial inflammatory response (by TNF- 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 epicatechine, significantly reduced all the above parameters and sustained endothelial-type NOS activity. These findings provide evidence that EGCG, likely 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.

Key words: apoptosis, asthma-like reaction, eosinophils, epigallocatechine-3-gallate, nitric oxide, nitric oxide synthase