全球水烟草吸烟的患病率正在增加。尽管对水烟吸烟（WPS）对心肺、肾脏和生殖系统的影响有着详细的记录，但对其对肝脏的不良影响知之甚少。因此，我们的研究旨在评估WPS吸入对肝脏的影响和潜在机制，包括一周或四周的时间。小鼠每天暴露于WPS 30分钟，每周五天，而对照小鼠则暴露于清洁空气中。光学显微镜分析显示，WPS吸入引起了免疫细胞（中性粒细胞和淋巴细胞）的浸润，同时伴随着肝细胞液泡变性。到四周时点，电子显微镜分析显示，WPS吸入导致线粒体数量增加，并伴随着肝细胞质膜的脱落。WPS暴露导致血液中肝酶丙氨酸转氨酶和天冬氨酸转氨酶活性的显著升高。此外，WPS吸入增加了肝组织均匀物中脂质过氧化和活性氧物种水平，并扰乱了抗氧化剂谷胱甘肽的水平。WPS暴露组中P乳头头活性因子、白细胞介素（IL）-6和IL-1β等促炎细胞因子浓度显著增加。此外，WPS吸入引起DNA损伤和蛋白酶-3、细胞色素C和缺氧诱导因子1α水平显著增加，并改变了线粒体复合物I、II、III和IV的活性。我们的发现提供了WPS吸入引起肝脏形态学变化、氧化应激、炎症、DNA损伤、细胞凋亡和线粒体活性改变的证据。版权所有 © 2023。由Elsevier Inc.发表。

The global prevalence of waterpipe tobacco smoking is increasing. Although the cardiorespiratory, renal, and reproductive effects of waterpipe smoking (WPS) are well-documented, there is limited knowledge regarding its adverse impact on the liver. Therefore, our study aimed to assess the effects and potential mechanisms of WPS inhalation for one or four weeks on the liver.Mice were exposed to WPS for 30 min per day, five days per week, while control mice were exposed to clean air.Analysis using light microscopy revealed the infiltration of immune cells (neutrophils and lymphocytes) accompanied by vacuolar hepatic degeneration upon WPS inhalation. At the four-week timepoint, electron microscopy analysis demonstrated an increased number of mitochondria with a concomitant pinching-off of hepatocyte plasma membranes. WPS exposure led to a significant rise in the activities of liver enzymes alanine aminotransferase and aspartate aminotransferase in the bloodstream. Additionally, WPS inhalation elevated lipid peroxidation and reactive oxygen species levels and disrupted the levels of the antioxidant glutathione in liver tissue homogenates. The concentration of proinflammatory cytokines, including tumor necrosis factor α, interleukin (IL)-6, and IL-1β, was significantly increased in the WPS-exposed group. Furthermore, WPS inhalation induced DNA damage and a significant increase in the levels of cleaved caspase-3, cytochrome C and hypoxia-inducible factor 1α along with alterations in the activity of mitochondrial complexes I, II, III and IV.Our findings provide evidence that WPS inhalation triggers changes in liver morphology, oxidative stress, inflammation, DNA damage, apoptosis, and alterations in mitochondrial activity.Copyright © 2023. Published by Elsevier Inc.