A Novel Class of Dual-Acting DCH-CORMs Counteracts Oxidative Stress-Induced Inflammation in Human Primary Tenocytes
Carbon monoxide (CO) can prevent cell and tissue damage by restoring redox homeostasis and counteracting inflammation. CO-releasing molecules (CORMs) can release a controlled amount of CO to cells and are emerging as a safer therapeutic alternative to delivery of CO in vivo. Sustained oxidative stre...
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2021
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oai:doaj.org-article:b2ff742f5df44003bbfc475b14a2710c2021-11-25T16:29:17ZA Novel Class of Dual-Acting DCH-CORMs Counteracts Oxidative Stress-Induced Inflammation in Human Primary Tenocytes10.3390/antiox101118282076-3921https://doaj.org/article/b2ff742f5df44003bbfc475b14a2710c2021-11-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1828https://doaj.org/toc/2076-3921Carbon monoxide (CO) can prevent cell and tissue damage by restoring redox homeostasis and counteracting inflammation. CO-releasing molecules (CORMs) can release a controlled amount of CO to cells and are emerging as a safer therapeutic alternative to delivery of CO in vivo. Sustained oxidative stress and inflammation can cause chronic pain and disability in tendon-related diseases, whose therapeutic management is still a challenge. In this light, we developed three small subsets of 1,5-diarylpyrrole and pyrazole dicobalt(0)hexacarbonyl (DCH)-CORMs to assess their potential use in musculoskeletal diseases. A myoglobin-based spectrophotometric assay showed that these CORMs act as slow and efficient CO-releasers. Five selected compounds were then tested on human primary-derived tenocytes before and after hydrogen peroxide stimulation to assess their efficacy in restoring cell redox homeostasis and counteracting inflammation in terms of PGE<sub>2</sub> secretion. The obtained results showed an improvement in tendon homeostasis and a cytoprotective effect, reflecting their activity as CO-releasers, and a reduction of PGE<sub>2</sub> secretion. As these compounds contain structural fragments of COX-2 selective inhibitors, we hypothesized that such a composite mechanism of action results from the combination of CO-release and COX-2 inhibition and that these compounds might have a potential role as dual-acting therapeutic agents in tendon-derived diseases.Federico AppetecchiaSara ConsalviEmanuela BerrinoMarialucia GalloriniArianna GraneseCristina CampestreSimone CarradoriMariangela BiavaGiovanna PoceMDPI AGarticleCO-releasing moleculestenocytesPGE<sub>2</sub>1,5-diarylpyrrole1,5-diarylpyrazolecarbon monoxideTherapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1828, p 1828 (2021) |
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| collection |
DOAJ |
| language |
EN |
| topic |
CO-releasing molecules tenocytes PGE<sub>2</sub> 1,5-diarylpyrrole 1,5-diarylpyrazole carbon monoxide Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
CO-releasing molecules tenocytes PGE<sub>2</sub> 1,5-diarylpyrrole 1,5-diarylpyrazole carbon monoxide Therapeutics. Pharmacology RM1-950 Federico Appetecchia Sara Consalvi Emanuela Berrino Marialucia Gallorini Arianna Granese Cristina Campestre Simone Carradori Mariangela Biava Giovanna Poce A Novel Class of Dual-Acting DCH-CORMs Counteracts Oxidative Stress-Induced Inflammation in Human Primary Tenocytes |
| description |
Carbon monoxide (CO) can prevent cell and tissue damage by restoring redox homeostasis and counteracting inflammation. CO-releasing molecules (CORMs) can release a controlled amount of CO to cells and are emerging as a safer therapeutic alternative to delivery of CO in vivo. Sustained oxidative stress and inflammation can cause chronic pain and disability in tendon-related diseases, whose therapeutic management is still a challenge. In this light, we developed three small subsets of 1,5-diarylpyrrole and pyrazole dicobalt(0)hexacarbonyl (DCH)-CORMs to assess their potential use in musculoskeletal diseases. A myoglobin-based spectrophotometric assay showed that these CORMs act as slow and efficient CO-releasers. Five selected compounds were then tested on human primary-derived tenocytes before and after hydrogen peroxide stimulation to assess their efficacy in restoring cell redox homeostasis and counteracting inflammation in terms of PGE<sub>2</sub> secretion. The obtained results showed an improvement in tendon homeostasis and a cytoprotective effect, reflecting their activity as CO-releasers, and a reduction of PGE<sub>2</sub> secretion. As these compounds contain structural fragments of COX-2 selective inhibitors, we hypothesized that such a composite mechanism of action results from the combination of CO-release and COX-2 inhibition and that these compounds might have a potential role as dual-acting therapeutic agents in tendon-derived diseases. |
| format |
article |
| author |
Federico Appetecchia Sara Consalvi Emanuela Berrino Marialucia Gallorini Arianna Granese Cristina Campestre Simone Carradori Mariangela Biava Giovanna Poce |
| author_facet |
Federico Appetecchia Sara Consalvi Emanuela Berrino Marialucia Gallorini Arianna Granese Cristina Campestre Simone Carradori Mariangela Biava Giovanna Poce |
| author_sort |
Federico Appetecchia |
| title |
A Novel Class of Dual-Acting DCH-CORMs Counteracts Oxidative Stress-Induced Inflammation in Human Primary Tenocytes |
| title_short |
A Novel Class of Dual-Acting DCH-CORMs Counteracts Oxidative Stress-Induced Inflammation in Human Primary Tenocytes |
| title_full |
A Novel Class of Dual-Acting DCH-CORMs Counteracts Oxidative Stress-Induced Inflammation in Human Primary Tenocytes |
| title_fullStr |
A Novel Class of Dual-Acting DCH-CORMs Counteracts Oxidative Stress-Induced Inflammation in Human Primary Tenocytes |
| title_full_unstemmed |
A Novel Class of Dual-Acting DCH-CORMs Counteracts Oxidative Stress-Induced Inflammation in Human Primary Tenocytes |
| title_sort |
novel class of dual-acting dch-corms counteracts oxidative stress-induced inflammation in human primary tenocytes |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/b2ff742f5df44003bbfc475b14a2710c |
| work_keys_str_mv |
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