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

Abstract

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.

Flavours and flavourings in waterpipe products: a comparison between tobacco, herbal molasses and steam stones

“…4 6 12-16 Not only do flavours contribute to attractiveness, the flavouring ingredients, from now on referred to as 'flavourings', can be hazardous too. [17][18][19] Flavoured waterpipe tobacco caused higher toxicity than unflavoured waterpipe tobacco in mice, when looking at different inflammatory and oxidative stress biomarkers. 17 Also, flavourings found in waterpipe tobacco such as limonene, linalool and eugenol are known as being allergenic in human skin.…”

“…[17][18][19] Flavoured waterpipe tobacco caused higher toxicity than unflavoured waterpipe tobacco in mice, when looking at different inflammatory and oxidative stress biomarkers. 17 Also, flavourings found in waterpipe tobacco such as limonene, linalool and eugenol are known as being allergenic in human skin. 18 Tobacco products, herbal products for smoking and products such as e-cigarettes and e-liquids, are covered by the Tobacco Products Directive 2014/40/EU (TPD).…”

Effect of smoking cessation on chronic waterpipe smoke inhalation-induced airway hyperresponsiveness, inflammation, and oxidative stress

“…In humans, it has been shown that WPS induces augmentation of markers of DNA injury including 8-OH-dG and cytochrome P450 1A1 and induces the inhibition of DNA repair genes (46). We have experimentally shown that WPS inhalation in mice can cause DNA injury in various organs including the lung and the heart (18,24,28). It is recognized that DNA damage may cause apoptosis and that caspase-3 is a member of the caspase enzyme family that plays an important role in the execution of apoptosis in COPD (47,48).…”

“…The mean numbers of macrophages, neutrophils, and lymphocytes were then changed from per HPF to per mm 2 (1 mm 2 = 4 HPFs). The quantification in all the four studied groups was performed randomly on 10 HPFs in each section (24,25).…”

Differences in oxidative stress profile in adolescents smoking waterpipe versus cigarettes: The Irbid TRY Project

“…In animal models, exposure to Wp smoke has been shown to cause oxidative damage and subsequent tissue injury to various body organs including the lungs (Khabour et al, 2018;Khan, Sundar, & Rahman, 2018;Nemmar, Al-Salam, Beegam, Yuvaraju, & Ali, 2020a), heart (Al-Sawalha, Al-Filali, Nemmar et al, 2020b), brain (Alqudah, Alzoubi, Ma'Abrih, & Khabour, 2018;Alzoubi, Halboup, Alomari, & Khabour, 2019a, kidney (Al-Sawalha, Alsari, Khabour, & Alzoubi, 2019c;Nemmar et al, 2020c;Rababa'h, Sultan, Alzoubi, Khabour, & Ababneh, 2016), liver (Charab, Abouzeinab, & Moustafa, 2016), and reproductive organs (Ali, 2017;Al-Sawalha, Almahmmod, Alzoubi, Khabour, & Alyacoub, 2019b). These alterations include induction of oxygen-reactive species, lipid peroxidation, and alteration of antioxidative enzyme activities (Badran & Laher, 2020).…”