Abstract
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.
Footnotes
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This work was supported by a grant from the Italian Ministry of Education, University and Research (Programma di Ricerca Scientifica di Interesse Nazionale Cofinanziati dal Ministero dell'Istruzione, dell'Università e della Ricerca 2002 to D.B. and H.S.) and by the Cassa di Risparmio di Verona Project (H.S.).
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doi:10.1124/jpet.106.102178.
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ABBREVIATIONS: NO, nitric oxide; NOS, nitric-oxide synthase; nNOS, neuronal nitric-oxide synthase; eNOS, endothelial nitric-oxide synthase; iNOS, inducible nitric-oxide synthase; TNF, tumor necrosis factor; EGCG, epigallocatechin-3-gallate; PBS, phosphate-buffered saline; BAL, bronchoalveolar lavage; eMBP, major basic protein; 8OHdG, 8-hydroxy-2-deoxyguanosine; SOD, superoxide dismutase; NBT, nitro blue tetrazolium; Chaps, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid; ANOVA, analysis of variance.
- Received February 2, 2006.
- Accepted March 7, 2006.
- The American Society for Pharmacology and Experimental Therapeutics
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