Protective effects of nootkatone against particles-induced lung injury caused by diesel exhaust is mediated via the NF-?B pathway

Numerous studies have shown that acute particulate air pollution exposure is linked with pulmonary adverse effects. Nootkatone, a constituent of grapefruit, has antioxidant and anti-inflammatory effects. However, the effect of nootkatone on lung toxicity has not been reported before. Here, we have evaluated the possible protective effect of nootkatone on diesel exhaust particles (DEP)-induced lung toxicity, and the possible mechanisms underlying these effects. Mice were intratracheally (i.t.) instilled with either DEP (30 µg/mouse) or saline (control). Nootkatone was given to mice by gavage 1 h before i.t. instillation with either DEP or saline. Twenty-four h following DEP exposure, several physiological and biochemical endpoints were assessed. Nootkatone pretreatment prevented the DEP-induced increase in airway resistance in vivo, decreased neutrophil infiltration in bronchoalveolar lavage fluid, and abated the macrophages and neutrophils infiltration in the lung interstitium assessed by histolopathology. Moreover, DEP caused an increase in lung concentrations of 8-isoprostane and tumor necrosis factor α, and decreased the reduced glutathione concentration and total nitric oxide activity. These actions were all alleviated by nootkatone pretreatment. Similarly, nootkatone prevented both DEP-induced DNA damage and proteolytic cleavage of caspase-3. Moreover, nootkatone inhibited nuclear factor-kappaB (NF-B) induced by DEP. We conclude that nootkatone prevented the ...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Occupational and Environmental Health Source Type: research