E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells

Previous studies in our laboratory have shown that nicotine exposure decreases glucose transport across the blood-brain barrier in ischemia-reperfusion conditions. We hypothesize that nicotine can also dysregulate brain parenchymal glucose utilization by altering glucose transporters with effects on sensitivity to ischemic stroke. In this study, we investigated the effects of nicotine exposure on neuronal glucose utilization using an in vitro ischemic stroke model. We also tested the effects of e-Cig vaping on ischemic brain glucose utilization using an acute brain slice technique. Primary cortical neurons and brain slices were subjected to oxygen-glucose deprivation followed by reoxygenation to mimic ischemia-reperfusion injury. We estimated brain cell glucose utilization by measuring the uptake of [ H] deoxy-d-glucose. Immunofluorescence and western blotting were done to characterize glucose transporters (GLUTs) and α7 nicotinic acetylcholine receptor (nAChR) expression. Furthermore, we used a glycolytic stress test to measure the effects of nicotine exposure on neuronal glucose metabolism. We observed that short- and long-term nicotine/cotinine exposure significantly decreased neuronal glucose utilization in ischemic conditions and the non-specific nAChR antagonist, mecamylamine reversed this effect. Nicotine/cotinine exposure also decreased neuronal GLUT1 and up-regulated α7 nAChR expression and decreased glycolysis. Exposure of mice to e-Cig vapor for 7 days likewise decreases brain glucose uptake under normoxic and ischemic conditions along with down-regulation of GLUT1 and GLUT3 expressions. These data support, from a cerebrovascular perspective, that nicotine and/or e-Cig vaping induce a state of glucose deprivation at the neurovascular unit which could lead to enhanced ischemic brain injury and/or stroke risk. OPEN PRACTICES: Open Science: This manuscript was awarded with the Open Materials Badge. For more information see: https://cos.io/our-services/open-science-badges/.

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“…A few recent studies suggest some toxic effects of e‐Cig exposure on vital organs, such as the lung and heart (Lee et al . ). Kaisar et al .…”

Section: Discussionmentioning

confidence: 97%

“…Recent studies found that e‐Cig use, commonly known as vaping, has been associated with increased carcinogenic potential (Lee et al . ), oxidative stress, and inflammatory activity (Muthumalage et al . ), as well as altered blood–brain barrier (BBB) permeability and worsened ischemic brain injury (Kaisar et al .…”

mentioning

confidence: 99%

Nicotine and electronic cigarette (E‐Cig) exposure decreases brain glucose utilization in ischemic stroke

Sifat

Vaidya

Kaisar

et al. 2018

Journal of Neurochemistry

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“…Furthermore, a case of acute myocardial infarction in a young man was recently reported after only 1 month of e‐cigarette use 90. Separate studies showed that e‐cigarettes also induce myocardial DNA damage,91 arterial stiffness14 and stroke92 in mice. While the current data indicate that short‐term exposure to e‐cigarettes is associated with cardiovascular harm, one can speculate that longer use/exposure to e‐cigarette would have even more detrimental effects; this will be the scope of future investigations.…”

Section: Discussionmentioning

confidence: 99%

Short‐Term E‐Cigarette Exposure Increases the Risk of Thrombogenesis and Enhances Platelet Function in Mice

Qasim

Karim

Silva‐Espinoza

et al. 2018

JAHA

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BackgroundCardiovascular disease is the main cause of death in the United States, with smoking being the primary preventable cause of premature death, and thrombosis being the main mechanism of cardiovascular mortality in smokers. Due to the perception that electronic/e‐cigarettes are “safer/less harmful” than conventional cigarettes, their usage—among a variety of ages—has increased tremendously during the past decade. Notably, there are limited studies regarding the negative effects of e‐cigarettes on the cardiovascular system, which is also the subject of significant debate.Methods and ResultsWe employed a passive e‐VapeTM vapor inhalation system and developed an in vivo whole‐body e‐cigarette mouse exposure protocol that mimics real‐life human exposure scenarios/conditions and investigated the effects of e‐cigarettes and clean air on platelet function and thrombogenesis. Our results show that platelets from e‐cigarette–exposed mice are hyperactive, with enhanced aggregation, dense and α granule secretion, activation of the αIIbβ3 integrin, phosphatidylserine expression, and Akt and ERK activation, when compared with clean air–exposed platelets. E‐cigarette–exposed platelets were also found to be resistant to inhibition by prostacyclin, relative to clean air. Furthermore, the e‐cigarette–exposed mice exhibited a shortened thrombosis occlusion and bleeding times.ConclusionsTaken together, our data demonstrate for the first time that e‐cigarettes alter physiological hemostasis and increase the risk of thrombogenic events. This is attributable, at least in part, to the hyperactive state of platelets. Thus, the negative health consequences of e‐cigarette exposure should not be underestimated and warrant further investigation.

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“…Electronic cigarette use is a crucial public health issue because of its perceived safety, widespread popularity, and insufficient data to test health outcomes. There have been reports of adverse health effects of e‐Cig use including enhanced carcinogenic potential (Lee et al, ), oxidative stress and inflammatory activity (Muthumalage et al, ), as well as altered BBB permeability and worsened ischemic brain injury (Kaisar, Villalba, et al, ). We have previously published that e‐Cig exposure can also decrease brain glucose utilization in ischemic stroke (Sifat et al, ).…”

Section: Discussionmentioning

confidence: 99%

Prenatal electronic cigarette exposure decreases brain glucose utilization and worsens outcome in offspring hypoxic–ischemic brain injury

Sifat

Nozohouri

Villalba

et al. 2020

Journal of Neurochemistry

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It has been shown that prenatal nicotine and tobacco smoke exposure can cause different neurobehavioral disorders in the offspring. We hypothesize that prenatal exposure to nicotine‐containing electronic cigarette (e‐Cig) vapor can predispose newborn to enhanced sensitivity to hypoxic–ischemic (HI) brain injury and impaired motor and cognitive functions. In this study, pregnant CD1 mice were exposed to e‐Cig vapor (2.4% nicotine). Primary cortical neurons isolated from e‐Cig exposed fetus were exposed to oxygen–glucose deprivation followed by reoxygenation (OGD/R) to mimic HI brain injury. Cell viability and glucose utilization were analyzed in these neurons. HI brain injury was induced in 8–9‐day‐old pups. Short‐term brain injury was evaluated by triphenyltetrazolium chloride staining. Long‐term motor and cognitive functions were evaluated by open field, novel object recognition, Morris water maze, and foot fault tests. Western blotting and immunofluorescence were done to characterize glucose transporters in offspring brain. We found that e‐Cig exposed neurons demonstrated decreased cell viability and glucose utilization in OGD/R. Prenatally e‐Cig exposed pups also had increased brain injury and edema 24 hr after HI brain injury. Further, in utero e‐Cig exposed offspring with HI brain injury displayed impaired memory, learning, and motor coordination at adolescence. Additionally, the expression of glucose transporters decreased in e‐Cig exposed offspring brain after HI brain injury. These results indicate that reduced glucose utilization can contribute to prenatal e‐Cig exposure induced worsened HI brain injury in offspring. This study is instrumental in elucidating the possible deleterious effects of e‐Cig use in the general population.

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E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells

Cited by 270 publications

References 58 publications

Nicotine and electronic cigarette (E‐Cig) exposure decreases brain glucose utilization in ischemic stroke

Nicotine and electronic cigarette (E‐Cig) exposure decreases brain glucose utilization in ischemic stroke

Short‐Term E‐Cigarette Exposure Increases the Risk of Thrombogenesis and Enhances Platelet Function in Mice

Prenatal electronic cigarette exposure decreases brain glucose utilization and worsens outcome in offspring hypoxic–ischemic brain injury

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