Tobramycin and Colistin display anti-inflammatory properties in CuFi-1 cystic fibrosis cell line.
- Publisher:
- Elsevier
- Publication Type:
- Journal Article
- Citation:
- European Journal of Pharmacology, 2021, 902, pp. 1-11
- Issue Date:
- 2021-07-05
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1-s2.0-S001429992100251X-main.pdf | 3.6 MB | Adobe PDF |
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Sheikh, Z | |
dc.contributor.author |
Bradbury, P |
|
dc.contributor.author | Reekie, TA | |
dc.contributor.author | Pozzoli, M | |
dc.contributor.author | Robinson, PD | |
dc.contributor.author | Kassiou, M | |
dc.contributor.author | Young, PM | |
dc.contributor.author | Ong, HX | |
dc.contributor.author | Traini, D | |
dc.date.accessioned | 2022-05-18T04:25:51Z | |
dc.date.available | 2021-04-07 | |
dc.date.available | 2022-05-18T04:25:51Z | |
dc.date.issued | 2021-07-05 | |
dc.identifier.citation | European Journal of Pharmacology, 2021, 902, pp. 1-11 | |
dc.identifier.issn | 0014-2999 | |
dc.identifier.issn | 1879-0712 | |
dc.identifier.uri | http://hdl.handle.net/10453/157486 | |
dc.description.abstract | Current cystic fibrosis (CF) treatment strategies are primarily focused on oral/inhaled anti-inflammatories and antibiotics, resulting in a considerable treatment burden for CF patients. Therefore, combination treatments consisting of anti-inflammatories with antibiotics could reduce the CF treatment burden. However, there is an imperative need to understand the potential drug-drug interactions of these combination treatments to determine their efficacy. Thus, this study aimed to determine the interactions of the anti-inflammatory agent Ibuprofen with each of the CF-approved inhaled antibiotics (Tobramycin, Colistin and its prodrug colistimethate sodium/Tadim) and anti-bacterial and anti-inflammatory efficacy. Chemical interactions of the Ibuprofen:antibiotic combinations were elucidated using High-Resolution Mass-Spectrometry (HRMS) and 1H NMR. HRMS showed pairing of Ibuprofen and Tobramycin, further confirmed by 1H NMR whilst no pairing was observed for either Ibuprofen:Colistin or Ibuprofen:Tadim combinations. The anti-bacterial activity of the combinations against Pseudomonas aeruginosa showed that neither paired nor non-paired Ibuprofen:antibiotic therapies altered the anti-bacterial activity. The anti-inflammatory efficacy of the combination therapies was next determined at two different concentrations (Low and High) using in vitro models of NuLi-1 (healthy) and CuFi-1 (CF) cell lines. Differential response in the anti-inflammatory efficacy of Ibuprofen:Tobramycin combination was observed between the two concentrations due to changes in the structural conformation of the paired Ibuprofen:Tobramycin complex at High concentration, confirmed by 1H NMR. In contrast, the non-pairing of the Ibuprofen:Colistin and Ibuprofen:Tadim combinations showed a significant decrease in IL-8 secretion at both the concentrations. Importantly, all antibiotics alone showed anti-inflammatory properties, highlighting the inherent anti-inflammatory properties of these antibiotics. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.publisher | Elsevier | |
dc.relation.ispartof | European Journal of Pharmacology | |
dc.relation.isbasedon | 10.1016/j.ejphar.2021.174098 | |
dc.rights | info:eu-repo/semantics/closedAccess | |
dc.subject | 0801 Artificial Intelligence and Image Processing, 1115 Pharmacology and Pharmaceutical Sciences, 1701 Psychology, 1702 Cognitive Sciences | |
dc.subject.classification | Behavioral Science & Comparative Psychology | |
dc.subject.classification | Pharmacology & Pharmacy | |
dc.subject.mesh | Anti-Bacterial Agents | |
dc.subject.mesh | Anti-Inflammatory Agents, Non-Steroidal | |
dc.subject.mesh | Cell Line | |
dc.subject.mesh | Cell Survival | |
dc.subject.mesh | Colistin | |
dc.subject.mesh | Cystic Fibrosis | |
dc.subject.mesh | Drug Combinations | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Ibuprofen | |
dc.subject.mesh | Inflammation | |
dc.subject.mesh | Interleukin-8 | |
dc.subject.mesh | Lipopolysaccharides | |
dc.subject.mesh | Pseudomonas aeruginosa | |
dc.subject.mesh | Tobramycin | |
dc.subject.mesh | Anti-Bacterial Agents | |
dc.subject.mesh | Anti-Inflammatory Agents, Non-Steroidal | |
dc.subject.mesh | Cell Line | |
dc.subject.mesh | Cell Survival | |
dc.subject.mesh | Colistin | |
dc.subject.mesh | Cystic Fibrosis | |
dc.subject.mesh | Drug Combinations | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Ibuprofen | |
dc.subject.mesh | Inflammation | |
dc.subject.mesh | Interleukin-8 | |
dc.subject.mesh | Lipopolysaccharides | |
dc.subject.mesh | Pseudomonas aeruginosa | |
dc.subject.mesh | Tobramycin | |
dc.subject.mesh | Cell Line | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Pseudomonas aeruginosa | |
dc.subject.mesh | Cystic Fibrosis | |
dc.subject.mesh | Inflammation | |
dc.subject.mesh | Ibuprofen | |
dc.subject.mesh | Colistin | |
dc.subject.mesh | Lipopolysaccharides | |
dc.subject.mesh | Tobramycin | |
dc.subject.mesh | Anti-Inflammatory Agents, Non-Steroidal | |
dc.subject.mesh | Interleukin-8 | |
dc.subject.mesh | Drug Combinations | |
dc.subject.mesh | Anti-Bacterial Agents | |
dc.subject.mesh | Cell Survival | |
dc.title | Tobramycin and Colistin display anti-inflammatory properties in CuFi-1 cystic fibrosis cell line. | |
dc.type | Journal Article | |
utslib.citation.volume | 902 | |
utslib.location.activity | Netherlands | |
utslib.for | 0801 Artificial Intelligence and Image Processing | |
utslib.for | 1115 Pharmacology and Pharmaceutical Sciences | |
utslib.for | 1701 Psychology | |
utslib.for | 1702 Cognitive Sciences | |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Engineering and Information Technology | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering | |
utslib.copyright.status | closed_access | * |
pubs.consider-herdc | false | |
dc.date.updated | 2022-05-18T04:25:44Z | |
pubs.publication-status | Published | |
pubs.volume | 902 |
Abstract:
Current cystic fibrosis (CF) treatment strategies are primarily focused on oral/inhaled anti-inflammatories and antibiotics, resulting in a considerable treatment burden for CF patients. Therefore, combination treatments consisting of anti-inflammatories with antibiotics could reduce the CF treatment burden. However, there is an imperative need to understand the potential drug-drug interactions of these combination treatments to determine their efficacy. Thus, this study aimed to determine the interactions of the anti-inflammatory agent Ibuprofen with each of the CF-approved inhaled antibiotics (Tobramycin, Colistin and its prodrug colistimethate sodium/Tadim) and anti-bacterial and anti-inflammatory efficacy. Chemical interactions of the Ibuprofen:antibiotic combinations were elucidated using High-Resolution Mass-Spectrometry (HRMS) and 1H NMR. HRMS showed pairing of Ibuprofen and Tobramycin, further confirmed by 1H NMR whilst no pairing was observed for either Ibuprofen:Colistin or Ibuprofen:Tadim combinations. The anti-bacterial activity of the combinations against Pseudomonas aeruginosa showed that neither paired nor non-paired Ibuprofen:antibiotic therapies altered the anti-bacterial activity. The anti-inflammatory efficacy of the combination therapies was next determined at two different concentrations (Low and High) using in vitro models of NuLi-1 (healthy) and CuFi-1 (CF) cell lines. Differential response in the anti-inflammatory efficacy of Ibuprofen:Tobramycin combination was observed between the two concentrations due to changes in the structural conformation of the paired Ibuprofen:Tobramycin complex at High concentration, confirmed by 1H NMR. In contrast, the non-pairing of the Ibuprofen:Colistin and Ibuprofen:Tadim combinations showed a significant decrease in IL-8 secretion at both the concentrations. Importantly, all antibiotics alone showed anti-inflammatory properties, highlighting the inherent anti-inflammatory properties of these antibiotics.
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