{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:57:47Z","timestamp":1790315867680,"version":"4.1.0"},"reference-count":84,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"College of Medicine and Health Sciences","award":["12M167"],"award-info":[{"award-number":["12M167"]}]},{"name":"College of Medicine and Health Sciences","award":["12R166"],"award-info":[{"award-number":["12R166"]}]},{"name":"Zayed Center for Health Sciences","award":["12M167"],"award-info":[{"award-number":["12M167"]}]},{"name":"Zayed Center for Health Sciences","award":["12R166"],"award-info":[{"award-number":["12R166"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>While the pulmonary effects of regular waterpipe smoking (R-WPS) are well-defined, the impact of occasional waterpipe smoking (O-WPS) on the lungs remains less established. This study investigated the pulmonary toxicity and underlying mechanisms of O-WPS versus R-WPS following 6 months of exposure, focusing on histopathology, inflammation in the lung, bronchoalveolar lavage fluid (BALF), and plasma, as well as oxidative stress, genotoxicity, mitochondrial dysfunction, and the expression of mitogen-activated protein kinases (MAPKs) in lung homogenates. Exposure to both O-WPS and R-WPS resulted in significant histological changes, including increased numbers of alveolar macrophages and lymphocytes, as well as interstitial fibrosis. Only R-WPS increased the number of neutrophil polymorphs and plasma cells. R-WPS also significantly increased the chemokines CXCL1, CXCL2, and CCL2 in the lung, BALF, and plasma, while O-WPS increased CXCL1 and CXCL2 in the lung and CXCL1 in the plasma. Both exposure regimens significantly increased lung injury markers, including matrix metalloproteinase-9 and myeloperoxidase. Additionally, R-WPS induced a significant increase in the cytokines IL1\u03b2, IL6, and TNF\u03b1 in the lung, BALF, and plasma, while O-WPS elevated IL1\u03b2 and IL6 in the lung. Oxidative stress was observed, with increased levels of thiobarbituric acid reactive substances and superoxide dismutase in both the O-WPS and R-WPS groups. Exposure to either O-WPS or R-WPS triggered genotoxicity and altered mitochondrial complex activities. R-WPS exposure also resulted in elevated expression of p-JNK\/JNK, p-ERK\/ERK, and p-p38\/p38, while O-WPS augmented the p-ERK\/ERK ratio in the lungs. Taken together, these findings indicate that both O-WPS and R-WPS contribute to lung injury and induce inflammation, oxidative stress, genotoxicity, and mitochondrial dysfunction, with R-WPS having a more pronounced effect. These effects were associated with the activation of MAPKs.<\/jats:p>","DOI":"10.3390\/ijms26010430","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T10:40:52Z","timestamp":1736160052000},"page":"430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Chronic Exposure to Two Regimens of Waterpipe Smoke Elicits Lung Injury, Genotoxicity, and Mitochondrial Impairment with the Involvement of MAPKs Activation in Mice"],"prefix":"10.3390","volume":"26","author":[{"given":"Naserddine","family":"Hamadi","sequence":"first","affiliation":[{"name":"Department of Environmental Sciences and Sustainability, College of Natural and Health Sciences, Zayed University, Abu Dhabi P.O. Box 144534, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhail","family":"Al-Salam","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"},{"name":"Zayed Center for Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumaya","family":"Beegam","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur Elena","family":"Zaaba","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozaz","family":"Elzaki","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0699-1015","authenticated-orcid":false,"given":"Abderrahim","family":"Nemmar","sequence":"additional","affiliation":[{"name":"Zayed Center for Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"},{"name":"Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Almomen, S., Aldossari, M., Khaleel, Y., Altamimi, M., Alharbi, O., Alsuwaydani, A., Almutairi, M., Alyousef, S., Hafiz, R., and Alshomer, F. (2023). Effect of glycerol concentration on levels of toxicants emissions from water-pipe tobacco smoking (WTS). BMC Public Health, 23.","DOI":"10.1186\/s12889-023-16740-2"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chaouachi, K. (2006). A critique of the WHO TobReg\u2019s \u201cAdvisory Note\u201d report entitled: \u201cWaterpipe tobacco smoking: Health effects, research needs and recommended actions by regulators\u201d. J. Negat. Results Biomed., 5.","DOI":"10.1186\/1477-5751-5-17"},{"key":"ref_3","first-page":"34","article-title":"Waterpipe (hookah) tobacco smoking among youth","volume":"41","author":"Martinasek","year":"2011","journal-title":"Curr. Probl. Pediatr. Adolesc. Health Care"},{"key":"ref_4","first-page":"91","article-title":"Waterpipe smoking: Not necessarily less hazardous than cigarette smoking: Possible consequences for (cardiovascular) disease","volume":"22","author":"Jukema","year":"2014","journal-title":"Neth. Heart J. Mon. J. Neth. Soc. Cardiol. Neth. Heart Found."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1617-9625-5-16","article-title":"Perceptions of hookah smoking harmfulness: Predictors and characteristics among current hookah users","volume":"5","author":"Aljarrah","year":"2009","journal-title":"Tob. Induc. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"i3","DOI":"10.1136\/tobaccocontrol-2014-051903","article-title":"The global epidemiology of waterpipe smoking","volume":"24","author":"Maziak","year":"2015","journal-title":"Tob. Control"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e10635","DOI":"10.1016\/j.heliyon.2022.e10635","article-title":"Discussion of waterpipe tobacco smoking on reddit","volume":"8","author":"Zheng","year":"2022","journal-title":"Heliyon"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.puhe.2024.03.008","article-title":"Association between waterpipe smoking and lung cancer: A multicentre case-control study in Iran","volume":"231","author":"Rashidian","year":"2024","journal-title":"Public Health"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Jawad, M., Bakir, A., Ali, M., and Grant, A. (2015). Impact of Waterpipe Tobacco Pack Health Warnings on Waterpipe Smoking Attitudes: A Qualitative Analysis among Regular Users in London. BioMed Res. Int., 2015.","DOI":"10.1155\/2015\/745865"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e917","DOI":"10.1161\/CIR.0000000000000671","article-title":"Water Pipe (Hookah) Smoking and Cardiovascular Disease Risk: A Scientific Statement From the American Heart Association","volume":"139","author":"Bhatnagar","year":"2019","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1158\/1055-9965.EPI-12-1422","article-title":"Comparison of nicotine and carcinogen exposure with water pipe and cigarette smoking","volume":"22","author":"Jacob","year":"2013","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.drugalcdep.2010.11.026","article-title":"Acute effects of waterpipe tobacco smoking: A double-blind, placebo-control study","volume":"116","author":"Blank","year":"2011","journal-title":"Drug Alcohol Depend."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"667","DOI":"10.3109\/08958378.2012.710918","article-title":"Acute exposure to waterpipe tobacco smoke induces changes in the oxidative and inflammatory markers in mouse lung","volume":"24","author":"Khabour","year":"2012","journal-title":"Inhal. Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.2147\/COPD.S106009","article-title":"Lung inflammation caused by inhaled toxicants: A review","volume":"11","author":"Wong","year":"2016","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"996","DOI":"10.26719\/2012.18.10.996","article-title":"Waterpipe smoking and dependence are associated with chronic bronchitis: A case-control study in Lebanon","volume":"18","author":"Salameh","year":"2012","journal-title":"East. Mediterr. Health J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1378\/chest.13-1499","article-title":"Chinese water-pipe smoking and the risk of COPD","volume":"146","author":"She","year":"2014","journal-title":"Chest"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1152\/japplphysiol.00194.2013","article-title":"Nose-only water-pipe smoking effects on airway resistance, inflammation, and oxidative stress in mice","volume":"115","author":"Nemmar","year":"2013","journal-title":"J. Appl. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1159\/000443050","article-title":"Chronic Exposure to Water-Pipe Smoke Induces Alveolar Enlargement, DNA Damage and Impairment of Lung Function","volume":"38","author":"Nemmar","year":"2016","journal-title":"Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e206436","DOI":"10.1001\/jamanetworkopen.2020.6436","article-title":"Dose-Response Association of Low-Intensity and Nondaily Smoking With Mortality in the United States","volume":"3","author":"Christensen","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"13","DOI":"10.33594\/000000491","article-title":"Comparative Study on the Chronic Vascular Responses Induced by Regular Versus Occasional Waterpipe Smoke Inhalation in Mice","volume":"56","author":"Hamadi","year":"2022","journal-title":"Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hamadi, N., Al-Salam, S., Beegam, S., Zaaba, N.E., Elzaki, O., and Nemmar, A. (2024). Impact of prolonged exposure to occasional and regular waterpipe smoke on cardiac injury, oxidative stress and mitochondrial dysfunction in male mice. Front. Physiol., 15.","DOI":"10.3389\/fphys.2024.1286366"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"337","DOI":"10.33549\/physiolres.935042","article-title":"Waterpipe smoke inhalation induces lung injury and aortic endothelial dysfunction in mice","volume":"72","author":"Nemmar","year":"2023","journal-title":"Physiol. Res."},{"key":"ref_23","first-page":"109","article-title":"Swimming Exercise Training Attenuates the Lung Inflammatory Response and Injury Induced by Exposing to Waterpipe Tobacco Smoke","volume":"12","author":"Nakhaee","year":"2020","journal-title":"Addict. Health"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.lfs.2018.03.034","article-title":"The effect of chronic exposure to waterpipe tobacco smoke on airway inflammation in mice","volume":"200","author":"Khabour","year":"2018","journal-title":"Life Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"L791","DOI":"10.1152\/ajplung.00420.2020","article-title":"Effect of smoking cessation on chronic waterpipe smoke inhalation-induced airway hyperresponsiveness, inflammation, and oxidative stress","volume":"320","author":"Nemmar","year":"2021","journal-title":"Am. J. Physiology. Lung Cell. Mol. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1186\/1465-9921-11-99","article-title":"Inflammatory changes in the airways of mice caused by cigarette smoke exposure are only partially reversed after smoking cessation","volume":"11","author":"Braber","year":"2010","journal-title":"Respir. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1080\/15412550902751738","article-title":"Alveolar macrophage recruitment and activation by chronic second hand smoke exposure in mice","volume":"6","author":"Woodruff","year":"2009","journal-title":"Copd"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"L377","DOI":"10.1152\/ajplung.00174.2015","article-title":"Cigarette smoke-induced necroptosis and DAMP release trigger neutrophilic airway inflammation in mice","volume":"310","author":"Pouwels","year":"2016","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"L602","DOI":"10.1152\/ajplung.00124.2016","article-title":"Cigarette smoke causes acute airway disease and exacerbates chronic obstructive lung disease in neonatal mice","volume":"311","author":"Jia","year":"2016","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1136\/thoraxjnl-2015-207886","article-title":"Cigarette smokers have exaggerated alveolar barrier disruption in response to lipopolysaccharide inhalation","volume":"71","author":"Moazed","year":"2016","journal-title":"Thorax"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1080\/00039899809605724","article-title":"Increase in memory (CD4+CD29+ and CD4+CD45RO+) T and naive (CD4+CD45RA+) T-cell subpopulations in smokers","volume":"53","author":"Tanigawa","year":"1998","journal-title":"Arch. Environ. Health"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature01322","article-title":"Inflammation and cancer","volume":"420","author":"Coussens","year":"2002","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1465-9921-9-7","article-title":"Bronchiolar chemokine expression is different after single versus repeated cigarette smoke exposure","volume":"9","author":"Betsuyaku","year":"2008","journal-title":"Respir. Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Allais, L., Verschuere, S., Maes, T., De Smet, R., Devriese, S., Gonzales, G.B., Peeters, H., Van Crombruggen, K., Bachert, C., and De Vos, M. (2020). Translational research into the effects of cigarette smoke on inflammatory mediators and epithelial TRPV1 in Crohn\u2019s disease. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0236657"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"L496","DOI":"10.1152\/ajplung.00290.2015","article-title":"p53- and PAI-1-mediated induction of C-X-C chemokines and CXCR2: Importance in pulmonary inflammation due to cigarette smoke exposure","volume":"310","author":"Tiwari","year":"2016","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Bratcher, P.E., Weathington, N.M., Nick, H.J., Jackson, P.L., Snelgrove, R.J., and Gaggar, A. (2012). MMP-9 cleaves SP-D and abrogates its innate immune functions in vitro. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041881"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1183\/09031936.00174612","article-title":"Alveolar macrophage proteinase\/antiproteinase expression in lung function and emphysema","volume":"43","author":"Ishii","year":"2014","journal-title":"Eur. Respir. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"81","DOI":"10.2147\/COPD.S190023","article-title":"Cigarette smoke-induced RANKL expression enhances MMP-9 production by alveolar macrophages","volume":"14","author":"Zhou","year":"2019","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1183\/09031936.00029307","article-title":"Myeloperoxidase modulates lung epithelial responses to pro-inflammatory agents","volume":"31","author":"Haegens","year":"2008","journal-title":"Eur. Respir. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"689","DOI":"10.3109\/08958378.2015.1085471","article-title":"Changes in the expression and protein level of matrix metalloproteinases after exposure to waterpipe tobacco smoke","volume":"27","author":"Khabour","year":"2015","journal-title":"Inhal. Toxicol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6450450","DOI":"10.1155\/2020\/6450450","article-title":"Comparative Study on Pulmonary Toxicity in Mice Induced by Exposure to Unflavoured and Apple- and Strawberry-Flavoured Tobacco Waterpipe Smoke","volume":"2020","author":"Nemmar","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1164\/rccm.201005-0718OC","article-title":"The role of matrix metalloproteinase-9 in cigarette smoke-induced emphysema","volume":"183","author":"Atkinson","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kim, M.D., Baumlin, N., Dennis, J.S., Yoshida, M., Kis, A., Aguiar, C., Schmid, A., Mendes, E., and Salathe, M. (2021). Losartan reduces cigarette smoke-induced airway inflammation and mucus hypersecretion. ERJ Open Res., 7.","DOI":"10.1183\/23120541.00394-2020"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Yu, D., Liu, X., Zhang, G., Ming, Z., and Wang, T. (2018). Isoliquiritigenin Inhibits Cigarette Smoke-Induced COPD by Attenuating Inflammation and Oxidative Stress via the Regulation of the Nrf2 and NF-\u03baB Signaling Pathways. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.01001"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"306","DOI":"10.4274\/MMJ.galenos.2022.45057","article-title":"Smoking Induces the Circulating Levels of Matrix Metalloproteinase-9 and Its Association with Cardiovascular Risk in Young Smokers","volume":"37","author":"Nath","year":"2022","journal-title":"Medeni. Med. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5346483","DOI":"10.1155\/2020\/5346483","article-title":"Clinical and Diagnostic Significance of Lactate Dehydrogenase and Its Isoenzymes in Animals","volume":"2020","author":"Klein","year":"2020","journal-title":"Vet. Med. Int."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e12258","DOI":"10.14814\/phy2.12258","article-title":"Early pulmonary events of nose-only water pipe (shisha) smoking exposure in mice","volume":"3","author":"Nemmar","year":"2015","journal-title":"Physiol. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.etap.2005.03.006","article-title":"Lactate dehydrogenase isoenzyme patterns upon chronic exposure to cigarette smoke: Protective effect of bacoside A","volume":"20","author":"Anbarasi","year":"2005","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Ranawat, P., Kaur, N., and Koul, A. (2023). Modulation of cigarette smoke induced alterations by aqueous Ocimum sanctum leaf extract in pulmonary tissue of rodents. Sci. Rep., 13.","DOI":"10.1038\/s41598-022-26152-8"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Zhou, L., Jian, T., Wan, Y., Huang, R., Fang, H., Wang, Y., Liang, C., Ding, X., and Chen, J. (2023). Luteolin Alleviates Oxidative Stress in Chronic Obstructive Pulmonary Disease Induced by Cigarette Smoke via Modulation of the TRPV1 and CYP2A13\/NRF2 Signaling Pathways. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25010369"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7459612","DOI":"10.1155\/2018\/7459612","article-title":"Exercise Training Mitigates Water Pipe Smoke Exposure-Induced Pulmonary Impairment via Inhibiting NF-\u03baB and Activating Nrf2 Signalling Pathways","volume":"2018","author":"Nemmar","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Belchamber, K., Hall, D.A., and Hourani, S.M. (2014). Smoking enhances the proinflammatory effects of nucleotides on cytokine release from human lung. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0099711"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"L1245","DOI":"10.1152\/ajplung.00253.2016","article-title":"Gene expression profiling of epigenetic chromatin modification enzymes and histone marks by cigarette smoke: Implications for COPD and lung cancer","volume":"311","author":"Sundar","year":"2016","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Frangie, C., and Daher, J. (2022). Role of myeloperoxidase in inflammation and atherosclerosis (Review). Biomed. Rep., 16.","DOI":"10.3892\/br.2022.1536"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Park, H.Y., Man, S.F., Tashkin, D., Wise, R.A., Connett, J.E., Anthonisen, N.A., and Sin, D.D. (2013). The relation of serum myeloperoxidase to disease progression and mortality in patients with chronic obstructive pulmonary disease (COPD). PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061315"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1056\/NEJMra1900475","article-title":"Update on the Pathogenesis of Chronic Obstructive Pulmonary Disease","volume":"381","author":"Hogg","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Barnes, P.J. (2022). Oxidative Stress in Chronic Obstructive Pulmonary Disease. Antioxidants, 11.","DOI":"10.3390\/antiox11050965"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1378\/chest.10-1833","article-title":"The acute effects of water-pipe smoking on the cardiorespiratory system","volume":"139","author":"Hakim","year":"2011","journal-title":"Chest"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e13579","DOI":"10.14814\/phy2.13579","article-title":"Strain- and sex-dependent pulmonary toxicity of waterpipe smoke in mouse","volume":"6","author":"Khan","year":"2018","journal-title":"Physiol. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Badran, M., and Laher, I. (2020). Waterpipe (shisha, hookah) smoking, oxidative stress and hidden disease potential. Redox Biol., 34.","DOI":"10.1016\/j.redox.2020.101455"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1080\/15376516.2018.1528650","article-title":"Genotoxic impact of long-term cigarette and waterpipe smoking on DNA damage and oxidative stress in healthy subjects","volume":"29","author":"Alsaad","year":"2019","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Martins, S.G., Zilh\u00e3o, R., Thorsteinsd\u00f3ttir, S., and Carlos, A.R. (2021). Linking Oxidative Stress and DNA Damage to Changes in the Expression of Extracellular Matrix Components. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.673002"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5","DOI":"10.18295\/squmj.6.2022.043","article-title":"Cytotoxic and Genotoxic Effects of Waterpipe on Oral Health Status: Systematic review and meta-analysis","volume":"23","author":"Grillo","year":"2023","journal-title":"Sultan Qaboos Univ. Med. J."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Nemmar, A., Al-Salam, S., Beegam, S., Zaaba, N.E., Elzaki, O., and Ali, B.H. (2023). Waterpipe smoke inhalation potentiates cardiac oxidative stress, inflammation, mitochondrial dysfunction, apoptosis and autophagy in experimental hypertension. Biomed. Pharmacother. Biomed. Pharmacother., 158.","DOI":"10.1016\/j.biopha.2022.114144"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1093\/carcin\/bgn034","article-title":"Associations between cigarette smoking and mitochondrial DNA abnormalities in buccal cells","volume":"29","author":"Tan","year":"2008","journal-title":"Carcinogenesis"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"L895","DOI":"10.1152\/ajplung.00180.2014","article-title":"Cigarette smoke extract affects mitochondrial function in alveolar epithelial cells","volume":"307","author":"Ballweg","year":"2014","journal-title":"Am. J. Physiology. Lung Cell. Mol. Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1165\/rcmb.2020-0008OC","article-title":"Mitochondrial Fission Mediated Cigarette Smoke-induced Pulmonary Endothelial Injury","volume":"63","author":"Wang","year":"2020","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1242\/jeb.00220","article-title":"Mitogen-activated protein kinases: New signaling pathways functioning in cellular responses to environmental stress","volume":"206","author":"Cowan","year":"2003","journal-title":"J. Exp. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1093\/carcin\/21.7.1423","article-title":"Roles of JNK, p38 and ERK mitogen-activated protein kinases in the growth inhibition and apoptosis induced by cadmium","volume":"21","author":"Chuang","year":"2000","journal-title":"Carcinogenesis"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1111\/j.1365-2249.2009.04033.x","article-title":"Mitogen activated protein kinases: A role in inflammatory bowel disease?","volume":"158","author":"Broom","year":"2009","journal-title":"Clin. Exp. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1002\/jcb.23151","article-title":"Cigarette smoke-induced skeletal muscle atrophy is associated with up-regulation of USP-19 via p38 and ERK MAPKs","volume":"112","author":"Liu","year":"2011","journal-title":"J. Cell. Biochem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1186\/s12964-024-01594-x","article-title":"Tobacco smoke condensate-induced senescence in endothelial cells was ameliorated by colchicine treatment via suppression of NF-\u03baB and MAPKs P38 and ERK pathways activation","volume":"22","author":"Khan","year":"2024","journal-title":"Cell Commun. Signal. CCS"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Restivo, I., Attanzio, A., Giardina, I.C., Di Gaudio, F., Tesoriere, L., and Allegra, M. (2022). Cigarette Smoke Extract Induces p38 MAPK-Initiated, Fas-Mediated Eryptosis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314730"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"H740","DOI":"10.1152\/ajpheart.00200.2013","article-title":"Cardiovascular effects of nose-only water-pipe smoking exposure in mice","volume":"305","author":"Nemmar","year":"2013","journal-title":"Am. J. Physiology. Heart Circ. Physiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"H329","DOI":"10.1152\/ajpheart.00450.2016","article-title":"Chronic exposure to water-pipe smoke induces cardiovascular dysfunction in mice","volume":"312","author":"Nemmar","year":"2017","journal-title":"Am. J. Physiology. Heart Circ. Physiol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Beegam, S., Al-Salam, S., Zaaba, N.E., Elzaki, O., Ali, B.H., and Nemmar, A. (2024). Effects of Waterpipe Smoke Exposure on Experimentally Induced Chronic Kidney Disease in Mice. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25010585"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1093\/ntr\/ntz109","article-title":"The Effect of a 30-Min Water-Pipe Smoking Session on Cognitive Measures and Cardio-Pulmonary Parameters","volume":"22","author":"Toukan","year":"2020","journal-title":"Nicotine Tob. Res. Off. J. Soc. Res. Nicotine Tob."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.5306\/wjco.v15.i10.1293","article-title":"Banxia xiexin decoction prevents the development of gastric cancer","volume":"15","author":"Zu","year":"2024","journal-title":"World J. Clin. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Houchen, C.J., Ghanem, S., Kaartinen, V., and Bumann, E.E. (2024). TGF-\u03b2 signaling in the cranial neural crest affects late-stage mandibular bone resorption and length. Front. Physiol., 15.","DOI":"10.3389\/fphys.2024.1435594"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Zaaba, N.E., Al-Salam, S., Beegam, S., Elzaki, O., Yasin, J., and Nemmar, A. (2023). Catalpol Attenuates Oxidative Stress and Inflammation via Mechanisms Involving Sirtuin-1 Activation and NF-\u03baB Inhibition in Experimentally-Induced Chronic Kidney Disease. Nutrients, 15.","DOI":"10.3390\/nu15010237"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Hardy, R.D., Coalson, J.J., Peters, J., Chaparro, A., Techasaensiri, C., Cantwell, A.M., Kannan, T.R., Baseman, J.B., and Dube, P.H. (2009). Analysis of pulmonary inflammation and function in the mouse and baboon after exposure to Mycoplasma pneumoniae CARDS toxin. PLoS ONE, 4.","DOI":"10.1371\/annotation\/616385db-f413-4f23-ba78-2fe626870e46"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1128\/IAI.00403-06","article-title":"Delayed inflammatory response to primary pneumonic plague occurs in both outbred and inbred mice","volume":"75","author":"Bubeck","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0378-4274(96)03847-7","article-title":"The contribution of cytotoxicity to DNA-effects in the single cell gel test (comet assay)","volume":"90","author":"Hartmann","year":"1997","journal-title":"Toxicol. Lett."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/0165-7992(95)90068-3","article-title":"Genotoxic effects of chemicals in the single cell gel (SCG) test with human blood cells in relation to the induction of sister-chromatid exchanges (SCE)","volume":"346","author":"Hartmann","year":"1995","journal-title":"Mutat. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/1\/430\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:23:52Z","timestamp":1759919032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/1\/430"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,6]]},"references-count":84,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["ijms26010430"],"URL":"https:\/\/doi.org\/10.3390\/ijms26010430","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,6]]}}}