Abstract

Background: Oxidative stress has been implicated in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD), and cigarette smoke (CS) is known to be one of the major sources of oxidants in the lungs. We postulated that acute administration of GSE (grape skin extract) would either reduce or protect the ALI (acute lung inflammation) produced by CS via NO release.
Material/Methods: We adopted a nutritional approach by investigating the inflammatory cells, metalloproteinase 9 (MMP-9) activity, and oxidative stress markers (superoxide dismutase – SOD; catalase – CAT; glutathione peroxidase (GPx) activities and malondialdehyde – MDA – levels) that play a role in the development of acute lung inflammation (ALI). Therefore, we tested an orally active antioxidant produced from grape skin manipulation (grape skin extract – GSE), in mice exposed to CS from 6 cigarettes a day for 5 days. In addition, we used a separate group treated with NG-nitro-L-arginine methyl ester (an NO inhibitor) to confirm nitric oxide (NO) involvement in GSE effects.
Results: We showed for the first time that administration of GSE inhibited ALI and oxidative damage induced by CS. This is associated with decreased MMP-9 activity, decreased number of inflammatory cells in the bronchoalveolar lavage fluid, and reduced levels of lipid peroxidation. Our results indicate that beneficial effects of GSE are NO-dependent.
Conclusions: The study indicates that alteration of the oxidant-antioxidant balance is important in the pathogenesis of CS-induced ALI and suggests lung protective effects of GSE treatment in the mouse.

Keywords: Pneumonia - pathology, Plant Extracts - pharmacology, Oxidative Stress - physiology, Oxidation-Reduction, Mice, Inbred C57BL, Matrix Metalloproteinase 9 - metabolism, Lung - pathology, Glutathione Peroxidase - metabolism, Catalase - metabolism, Biological Markers - metabolism, Smoking - adverse effects, Superoxide Dismutase - metabolism, Thiobarbituric Acid Reactive Substances - metabolism, Tobacco, Vitis - chemistry