Nebulized Menthol Impairs Mucociliary Clearance via TRPM8 and MUC5AC/MUC5B in Primary Airway Epithelial Cells

Baumlin, Nathalie; Silswal, Neerupma; Dennis, John S.; Niloy, Asef J.; Kim, Michael D.; Salathé, Matthias

doi:10.3390/ijms24021694

Cited by 6 publications

(2 citation statements)

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“…The functional significance of this finding is unknown. There is evidence that menthol 51 and nicotine 52 may alter airway mucus properties. JMi aerosol had higher nicotine concentrations than air controls in this study.…”

Section: Discussionmentioning

confidence: 99%

Effects of Short‐term Electronic(e)‐Cigarette Aerosol Exposure in the Mouse Larynx

Easwaran,

Maria,

Martinez

et al. 2023

The Laryngoscope

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ObjectivesThe effects of electronic cigarettes (e‐cigarettes) on the larynx are relatively unknown. This study examined the short‐term effects of e‐cigarette inhalation on cellular and inflammatory responses within the mouse laryngeal glottic and subglottic regions after exposure to pod‐based devices (JUUL).MethodsMale C57BL6/J mice (8–9 weeks) were assigned to control (n = 9), JUUL flavors Mint (JMi; n = 10) or Mango (JMa; n = 10). JUUL mice were exposed to 2 h/day for 1, 5, and 10 days using the inExpose inhalation system. Control mice were in room air. Vocal fold (VF) epithelial thickness, cell proliferation, subglandular area and composition, inflammatory cell infiltration, and surface topography were evaluated in the harvested larynges. Mouse body weight and urinary nicotine biomarkers were also measured. Chemical analysis of JUUL aerosols was conducted using selective ion flow tube mass spectrometry.ResultsJUUL‐exposed mice had reduced body weight after day 5. Urinary nicotine biomarker levels indicated successful JUUL exposure and metabolism. Quantitative analysis of JUUL aerosol indicated that chemical constituents differ between JMi and JMa flavors. VF epithelial thickness, cellular proliferation, glandular area, and surface topography remained unchanged after JUUL exposures. Acidic mucus content increased after 1 day of JMi exposure. VF macrophage and T‐cell levels slightly increased after 10 days of JMi exposures.ConclusionsShort‐term e‐cigarette exposures cause minimal flavor‐ and region‐specific cellular and inflammatory changes in the mouse larynx. This work provides a foundation for long‐term studies to determine if these responses are altered with multiple e‐cigarette components and concentrations.Level of EvidenceN/A Laryngoscope, 2023

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Section: Discussionmentioning

confidence: 99%

Effects of Short‐term Electronic(e)‐Cigarette Aerosol Exposure in the Mouse Larynx

Easwaran,

Maria,

Martinez

et al. 2023

The Laryngoscope

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“…As a result, smokers are more likely to hold the smoke and breath deeper [ 46 ], which in theory would lead to a higher particle deposition [ 47 ]. Additionally, study has reported a reduction in ciliary beating frequency following exposure to menthol-containing tobacco products, which impairs mucociliary clearance of deposited particle in airway [ 48 , 49 ]. Based on this, we had hypothesized that the overall deposition fraction would be higher with mentholated little cigars than the regular little cigars.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneous deposition of regular and mentholated little cigar smoke in the lungs of Sprague-Dawley rats

Lin,

Wallis,

Wong

et al. 2023

Part Fibre Toxicol

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Background Quantifying the dose and distribution of tobacco smoke in the respiratory system is critical for understanding its toxicity, addiction potential, and health impacts. Epidemiologic studies indicate that the incidence of lung tumors varies across different lung regions, suggesting there may be a heterogeneous deposition of smoke particles leading to greater health risks in specific regions. Despite this, few studies have examined the lobar spatial distribution of inhaled particles from tobacco smoke. This gap in knowledge, coupled with the growing popularity of little cigars among youth, underscores the need for additional research with little cigars. Results In our study, we analyzed the lobar deposition in rat lungs of smoke particles from combusted regular and mentholated Swisher Sweets little cigars. Twelve-week-old male and female Sprague-Dawley rats were exposed to smoke particles at a concentration of 84 ± 5 mg/m3 for 2 h, after which individual lung lobes were examined. We utilized Inductively Coupled Plasma Mass Spectrometry to quantify lobar chromium concentrations, serving as a smoke particle tracer. Our findings demonstrated an overall higher particle deposition from regular little cigars than from the mentholated ones. Higher particle deposition fraction was observed in the left and caudal lobes than other lobes. We also observed sex-based differences in the normalized deposition fractions among lobes. Animal study results were compared with the multi-path particle dosimetry (MPPD) model predictions, which showed that the model overestimated particle deposition in certain lung regions. Conclusions Our findings revealed that the particle deposition varied between different little cigar products. The results demonstrated a heterogenous deposition pattern, with higher particle deposition observed in the left and caudal lobes, especially with the mentholated little cigars. Additionally, we identified disparities between our measurements and the MPPD model. This discrepancy highlights the need to enhance the accuracy of models before extrapolating animal study results to human lung deposition. Overall, our study provides valuable insights for estimating the dose of little cigars during smoking for toxicity research.

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Respiratory Protective Effects of Perilla Leave Varieties (Perilla frutescens) Against Fine Particulate Matter (PM_2.5)‐induced Damage in Human Nasal Cells

Kim,

Kim

et al. 2024

Food Science & Nutrition

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Fine particulate matter (PM2.5) is known to exacerbate chronic respiratory disorders, primarily by inducing inflammatory responses and mucus overproduction. Perilla leaves are reported to have significant health benefits, such as antioxidant, antibacterial, and antiallergic properties, attributed to phenolic compounds that vary depending on genetic diversity. In this study, flavonoid‐rich extracts (FRE) from 56 perilla leaf varieties and genetic resources were prepared and screened using a mass screening system. The screening focused on evaluating their anti‐inflammatory, mucus‐reducing, and respiratory protective effects against PM2.5‐induced damage in human nasal cells (RPMI2650). Parameters such as cell viability, nitric oxide (NO) levels, and mucus secretion factor (MUC5AC) concentrations were assessed. Among the 56 varieties, Perilla frutescens var. crispa (YCPL706), sourced from Ulleung Island, Korea, exhibited the highest cell viability (112.50%, 100 μg/mL), lowest NO concentration (9.98 μM, 100 μg/mL), and MUC5AC level (78.65 ng/mL, 100 μg/mL). Further evaluation of YCPL706 FRE demonstrated significant respiratory protective effects, including the inhibition of pro‐inflammatory cytokines (TNF‐α, IL‐6, and IL‐1β), MUC5AC, and oxidative stress factors (MDA and ROS), compared to the control cultivar Namcheon. YCPL706 also showed strong antibacterial activity against Pseudomonas aeruginosa (minimum inhibitory concentration: 5 mg/mL). These findings suggest that the genetic resource YCPL706 is a promising candidate for combating PM2.5‐induced respiratory damage due to its potent anti‐inflammatory, antioxidant, and antibacterial properties.

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Nebulized Menthol Impairs Mucociliary Clearance via TRPM8 and MUC5AC/MUC5B in Primary Airway Epithelial Cells

Cited by 6 publications

References 46 publications

Effects of Short‐term Electronic(e)‐Cigarette Aerosol Exposure in the Mouse Larynx

Effects of Short‐term Electronic(e)‐Cigarette Aerosol Exposure in the Mouse Larynx

Heterogeneous deposition of regular and mentholated little cigar smoke in the lungs of Sprague-Dawley rats

Respiratory Protective Effects of Perilla Leave Varieties (Perilla frutescens) Against Fine Particulate Matter (PM_2.5)‐induced Damage in Human Nasal Cells

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Nebulized Menthol Impairs Mucociliary Clearance via TRPM8 and MUC5AC/MUC5B in Primary Airway Epithelial Cells

Cited by 6 publications

References 46 publications

Effects of Short‐term Electronic(e)‐Cigarette Aerosol Exposure in the Mouse Larynx

Effects of Short‐term Electronic(e)‐Cigarette Aerosol Exposure in the Mouse Larynx

Heterogeneous deposition of regular and mentholated little cigar smoke in the lungs of Sprague-Dawley rats

Respiratory Protective Effects of Perilla Leave Varieties (Perilla frutescens) Against Fine Particulate Matter (PM2.5)‐induced Damage in Human Nasal Cells

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Respiratory Protective Effects of Perilla Leave Varieties (Perilla frutescens) Against Fine Particulate Matter (PM_2.5)‐induced Damage in Human Nasal Cells