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INFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA
Department of Anatomy, Histology, and Forensic Medicine, Section of Histology (D.B., S.N.) and Department of Preclinical and Clinical Pharmacology (L.G., E.M.), University of Florence, Florence, Italy; and Department of Morphological-Biomedical Sciences, Section of Biochemistry (A.C., M.M., H.S.) and Department of Pediatrics (Y.S.), University of Verona, Verona, Italy
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-
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.
Address correspondence to: Hisanori Suzuki, Department of Morphological-Biomedical Sciences, Section of Biochemistry, University of Verona, Strada Le Grazie 8, I-37134 Verona, Italy. E-mail: hisanori.suzuki{at}univr.it