Epigallocatechin-3-gallate reduces allergen-induced asthma-like reaction in sensitized guinea pigs.
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.
Bani
Daniele
D
Department of Anatomy, Section of Histology, University of Florence, Florence, Italy.
Giannini
Lucia
L
Ciampa
Anna
A
Masini
Emanuela
E
Suzuki
Ylenia
Y
Menegazzi
Marta
M
Nistri
Silvia
S
Suzuki
Hisanori
H
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology
D000485:Allergens; D018927:Anti-Asthmatic Agents; D002392:Catechin; D010047:Ovalbumin; C045651:epigallocatechin gallate; D019001:Nitric Oxide Synthase