Aldehyde Trapping by ADX-102 Is Protective against Cigarette Smoke and Alcohol Mediated Lung Cell Injury
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,...
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MDPI AG
2022-03-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/3/393 |
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| author | Carmen A. Ochoa Claire G. Nissen Deanna D. Mosley Christopher D. Bauer Destiny L. Jordan Kristina L. Bailey Todd A. Wyatt |
| author_facet | Carmen A. Ochoa Claire G. Nissen Deanna D. Mosley Christopher D. Bauer Destiny L. Jordan Kristina L. Bailey Todd A. Wyatt |
| author_sort | Carmen A. Ochoa |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T20:05:03Z |
| format | Article |
| id | doaj.art-a8df4ec48b7741dabb172db6be666e6d |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T20:05:03Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-a8df4ec48b7741dabb172db6be666e6d2023-11-24T00:35:18ZengMDPI AGBiomolecules2218-273X2022-03-0112339310.3390/biom12030393Aldehyde Trapping by ADX-102 Is Protective against Cigarette Smoke and Alcohol Mediated Lung Cell InjuryCarmen A. Ochoa0Claire G. Nissen1Deanna D. Mosley2Christopher D. Bauer3Destiny L. Jordan4Kristina L. Bailey5Todd A. Wyatt6Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5910, USADepartment of Environmental, Agricultural and Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198-5910, USADepartment of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5910, USADepartment of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5910, USADepartment of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5910, USADepartment of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5910, USADepartment of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5910, USAMost 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.https://www.mdpi.com/2218-273X/12/3/393alcoholcigaretteAUDacetaldehydemalondialdehydelung |
| spellingShingle | Carmen A. Ochoa Claire G. Nissen Deanna D. Mosley Christopher D. Bauer Destiny L. Jordan Kristina L. Bailey Todd A. Wyatt Aldehyde Trapping by ADX-102 Is Protective against Cigarette Smoke and Alcohol Mediated Lung Cell Injury Biomolecules alcohol cigarette AUD acetaldehyde malondialdehyde lung |
| title | Aldehyde Trapping by ADX-102 Is Protective against Cigarette Smoke and Alcohol Mediated Lung Cell Injury |
| title_full | Aldehyde Trapping by ADX-102 Is Protective against Cigarette Smoke and Alcohol Mediated Lung Cell Injury |
| title_fullStr | Aldehyde Trapping by ADX-102 Is Protective against Cigarette Smoke and Alcohol Mediated Lung Cell Injury |
| title_full_unstemmed | Aldehyde Trapping by ADX-102 Is Protective against Cigarette Smoke and Alcohol Mediated Lung Cell Injury |
| title_short | Aldehyde Trapping by ADX-102 Is Protective against Cigarette Smoke and Alcohol Mediated Lung Cell Injury |
| title_sort | aldehyde trapping by adx 102 is protective against cigarette smoke and alcohol mediated lung cell injury |
| topic | alcohol cigarette AUD acetaldehyde malondialdehyde lung |
| url | https://www.mdpi.com/2218-273X/12/3/393 |
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