TY - JOUR
T1 - Chronic Exposure to Two Regimens of Waterpipe Smoke Elicits Lung Injury, Genotoxicity, and Mitochondrial Impairment with the Involvement of MAPKs Activation in Mice
AU - Hamadi, Naserddine
AU - Al-Salam, Suhail
AU - Beegam, Sumaya
AU - Zaaba, Nur Elena
AU - Elzaki, Ozaz
AU - Nemmar, Abderrahim
N1 - Publisher Copyright:
© 2025 by the authors.
PY - 2025/1
Y1 - 2025/1
N2 - 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 IL1β, IL6, and TNFα in the lung, BALF, and plasma, while O-WPS elevated IL1β 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.
AB - 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 IL1β, IL6, and TNFα in the lung, BALF, and plasma, while O-WPS elevated IL1β 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.
KW - inflammation
KW - lung
KW - occasional
KW - regular
KW - waterpipe smoke
UR - http://www.scopus.com/inward/record.url?scp=85214472591&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85214472591&partnerID=8YFLogxK
U2 - 10.3390/ijms26010430
DO - 10.3390/ijms26010430
M3 - Article
C2 - 39796284
AN - SCOPUS:85214472591
SN - 1661-6596
VL - 26
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 1
M1 - 430
ER -