Aldehyde trapping by ADX-102 is protective against cigarette smoke and alcohol mediated lung cell injury.

Details

• Personal Author:
  Bailey KL ; Bauer CD ; Jordan DL ; Mosley DD ; Nissen CG ; Ochoa CA ; Wyatt TA
• Description:
  Most individuals diagnosed with alcohol use disorders smoke cigarettes. Large concentrations of malondialdehyde and acetaldehyde are found in lungs co-exposed to cigarette smoke and alcohol. Aldehydes directly injure lungs and form aldehyde protein adducts, impacting epithelial functions. Recently, 2-(3-Amino-6-chloroquinolin-2-yl)propan-2-ol (ADX-102) was developed as an aldehyde-trapping drug. We hypothesized that aldehyde-trapping compounds are protective against lung injury derived from cigarette smoke and alcohol co-exposure. To test this hypothesis, we pretreated mouse ciliated tracheal epithelial cells with 0-100 µM of ADX-102 followed by co-exposure to 5% cigarette smoke extract and 50 mM of ethanol. Pretreatment with ADX-102 dose-dependently protected against smoke and alcohol induced cilia-slowing, decreases in bronchial epithelial cell wound repair, decreases in epithelial monolayer resistance, and the formation of MAA adducts. ADX-102 concentrations up to 100 µM showed no cellular toxicity. As protein kinase C (PKC) activation is a known mechanism for slowing cilia and wound repair, we examined the effects of ADX-102 on smoke and alcohol induced PKC epsilon activity. ADX-102 prevented early (3 h) activation and late (24 h) autodownregulation of PKC epsilon in response to smoke and alcohol. These data suggest that reactive aldehydes generated from cigarette smoke and alcohol metabolism may be potential targets for therapeutic intervention to reduce lung injury. [Description provided by NIOSH]
• Subjects:
  Alcoholic Beverages Aldehydes Formaldehyde Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety Smokers Tobacco Products

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• Keywords:
  Aldehydes; Lung Disorders; Cigarette Smoking; Cigarette Smoke; Alcohol; Ethanol; Proteins; Author Keywords: Alcohol; Cigarette; AUD; Acetaldehyde; Malondialdehyde; Lung
• ISSN:
  2218-273X
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Nebraska ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  12
• Issue:
  3
• NIOSHTIC Number:
  nn:20064857
• Citation:
  Biomolecules 2022 Mar; 12(3):393
• Contact Point Address:
  Todd A. Wyatt, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105
• Email:
  twyatt@unmc.edu
• CAS Registry Number:
  Ethanol (CAS RN 64-17-5)
• Federal Fiscal Year:
  2022
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• Start Date:
  20110901
• Source Full Name:
  Biomolecules
• End Date:
  20270831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:0b9111ae1888c045ed9bb6adec7324dd805e812e45745b091f470a819ea57bcbddd011d4f53c6927b1e5a287158ca9b4318b748d573ac435d050bd22dd82b9dc
• Download URL:
  https://stacks.cdc.gov/view/cdc/248636/cdc_248636_DS1.pdf
• File Type:
  [PDF - 1.52 MB ]