Aerosolized vitamin E acetate causes oxidative injury in mice and in alveolar macrophages.
Shotaro MatsumotoMaret G TraberScott W LeonardJaewoo ChoiXiaohui FangMazharul MaishanKatherine D WickKirk D JonesCarolyn S CalfeeJeffrey E GottsMichael A MatthayPublished in: American journal of physiology. Lung cellular and molecular physiology (2022)
Although vitamin E acetate (VEA) is suspected to play a causal role in the development of electronic-cigarette, or vaping, product use-associated lung injury (EVALI), the underlying biological mechanisms of pulmonary injury are yet to be determined. In addition, no study has replicated the systemic inflammation observed in humans in a murine EVALI model, nor investigated potential additive toxicity of viral infection in the setting of exposure to vaping products. To identify the mechanisms driving VEA-related lung injury and test the hypothesis that viral infection causes additive lung injury in the presence of aerosolized VEA, we exposed mice to aerosolized VEA for extended times, followed by influenza infection in some experiments. We used mass spectrometry to evaluate the composition of aerosolized VEA condensate and the VEA deposition in murine or human alveolar macrophages. Extended vaping for 28 days versus 15 days did not worsen lung injury but caused systemic inflammation in the murine EVALI model. Vaping plus influenza increased lung water compared with virus alone. Murine alveolar macrophages exposed to vaped VEA hydrolyzed the VEA to vitamin E with evidence of oxidative stress in the alveolar space and systemic circulation. Aerosolized VEA also induced cell death and chemokine release and reduced efferocytotic function in human alveolar macrophages in vitro. These findings provide new insights into the biological mechanisms of VEA toxicity.
Keyphrases
- oxidative stress
- cell death
- endothelial cells
- mass spectrometry
- diabetic rats
- pulmonary hypertension
- high resolution
- adipose tissue
- dna damage
- signaling pathway
- drug induced
- metabolic syndrome
- skeletal muscle
- insulin resistance
- ischemia reperfusion injury
- heat shock
- pluripotent stem cells
- single molecule
- atomic force microscopy
- stress induced
- capillary electrophoresis
- heat shock protein