PT  - JOURNAL ARTICLE
AU  - Daniele Bani
AU  - Lucia Giannini
AU  - Anna Ciampa
AU  - Emanuela Masini
AU  - Ylenia Suzuki
AU  - Marta Menegazzi
AU  - Silvia Nistri
AU  - Hisanori Suzuki
TI  - Epigallocatechin-3-Gallate Reduces Allergen-Induced Asthma-Like Reaction in Sensitized Guinea Pigs
AID  - 10.1124/jpet.106.102178
DP  - 2006 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1002--1011
VI  - 317
IP  - 3
4099  - http://jpet.aspetjournals.org/content/317/3/1002.short
4100  - http://jpet.aspetjournals.org/content/317/3/1002.full
SO  - J Pharmacol Exp Ther2006 Jun 01; 317
AB  - 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-α 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. The American Society for Pharmacology and Experimental Therapeutics