In the present study, we tested the antioxidant and anti-inflammatory potential of the plant flavonoid, fisetin against cigarette smoke-induced oxidative stress, and inflammation in rat lungs. Male Wistar rats were chronically exposed to cigarette smoke (CS) with or without administration of fisetin. Fisetin administration to CS-exposed rats resulted in a significant reduction in neutrophils and macrophages in bronchoalveolar lavage fluid as well as malondialdehyde, 3-nitrotyrosine, 8-isoprostane, tumor necrosis factor-alpha, interleukin-1beta, granulocyte macrophage-colony stimulating factor, interleukin-4, and interleukin-10 levels in lung tissues compared to those in CS-exposed rats not treated with fisetin. Fisetin also significantly augmented lung hemoxinase-1, glutathione peroxidase-2, reduced glutathione, superoxide dismutase, nitric oxide, and nuclear factor erythroid 2-related factor (Nrf2) levels in CS-exposed rats. In addition, a marked reversal in CS-induced histopathological changes was noted in fisetin-treated rats. Collectively, these data demonstrate the potential of fisetin to blunt CS-induced oxidative stress and inflammation in the lung and to prevent tissue damage via the Nrf2-mediated upregulation of antioxidant gene expression. PRACTICAL APPLICATIONS: In the present study, we found that the plant flavonoid, fisetin significantly abrogated the oxidative stress, inflammation, and tissue damage induced by cigarette smoke, a powerful pro-oxidant in rat lungs. Additionally, fisetin markedly reversed cigarette smoke-induced increases in neutrophil and macrophage cell populations in bronchoalveolar lavage fluid. These findings are particularly significant considering the association of cigarette smoking with increased oxidative stress and inflammation, which are central to the pathologies of a wide variety of chronic diseases including chronic obstructive pulmonary disease, cancer, and cardiovascular diseases. Therefore, the present work underscores the beneficial effects of the regular consumption of plant-based foods with medicinal properties for the effective prevention of these chronic diseases.
Keywords: antioxidants; cigarette smoke; fisetin; inflammation; oxidative stress.
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