Comparative Study on Pulmonary Toxicity in Mice Induced by Exposure to Unflavoured and Apple- and Strawberry-Flavoured Tobacco Waterpipe Smoke.

The use of flavoured tobacco products in waterpipe smoking (WPS) has increased its attractiveness and consumption. Nonetheless, the influence of flavourings on pulmonary toxicity caused by WPS remains unclear. Here, the pulmonary toxicity induced by plain (P)-WPS, apple-flavoured (AF)-WPS, and strawberry-flavoured (SF)-WPS (30 minutes/day, 5 days/week for 1 month) was investigated in mice. Control mice were exposed to air. Exposure to P-WPS or AF-WPS or SF-WPS induced a dose-dependent increase of airway hyperreactivity to methacholine. The histological evaluation of the lungs in all the WPS groups revealed the presence focal areas of dilated alveolar spaces and foci of widening of interalveolar spaces with inflammatory cells. In the lung, the activity of neutrophil elastase and myeloperoxidase and the concentrations of tumor necrosis factor-α and glutathione were increased by the exposure to P-WPS, AF-WPS, or SF-WPS. However, the levels of interleukin-6 and catalase were only increased in the AF-WPS and SF-WPS groups, while nitric oxide activity was only increased in the SF-WPS group. DNA injury was increased in all the WPS groups, but the concentration of cleaved caspase-3 was only elevated in the SF-WPS group. The exposure to either P-WPS or AF-WPS or SF-WPS increased the expression of nuclear factor kappa-B (NF-κB) in the lung. In conclusion, the exposure to P-WPS or AF-WPS or SF-WPS induces alterations in lung function and morphology and causes oxidative stress and inflammation via mechanisms that include activation of NF-κB. Overall, the toxicity of flavoured tobacco WPS, in particular SF-WPS, was found to be greater than that of unflavoured WPS.