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...

Full description

Saved in:
Bibliographic Details
Main Authors: Federico Appetecchia (Author), Sara Consalvi (Author), Emanuela Berrino (Author), Marialucia Gallorini (Author), Arianna Granese (Author), Cristina Campestre (Author), Simone Carradori (Author), Mariangela Biava (Author), Giovanna Poce (Author)
Format: Book
Published: MDPI AG, 2021-11-01T00:00:00Z.
Subjects:
Online Access:Connect to this object online.
Tags: Add Tag
No Tags, Be the first to tag this record!

MARC

LEADER 00000 am a22000003u 4500
001 doaj_b2ff742f5df44003bbfc475b14a2710c
042 |a dc 
100 1 0 |a Federico Appetecchia  |e author 
700 1 0 |a Sara Consalvi  |e author 
700 1 0 |a Emanuela Berrino  |e author 
700 1 0 |a Marialucia Gallorini  |e author 
700 1 0 |a Arianna Granese  |e author 
700 1 0 |a Cristina Campestre  |e author 
700 1 0 |a Simone Carradori  |e author 
700 1 0 |a Mariangela Biava  |e author 
700 1 0 |a Giovanna Poce  |e author 
245 0 0 |a A Novel Class of Dual-Acting DCH-CORMs Counteracts Oxidative Stress-Induced Inflammation in Human Primary Tenocytes 
260 |b MDPI AG,   |c 2021-11-01T00:00:00Z. 
500 |a 10.3390/antiox10111828 
500 |a 2076-3921 
520 |a 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. 
546 |a EN 
690 |a CO-releasing molecules 
690 |a tenocytes 
690 |a PGE<sub>2</sub> 
690 |a 1,5-diarylpyrrole 
690 |a 1,5-diarylpyrazole 
690 |a carbon monoxide 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Antioxidants, Vol 10, Iss 11, p 1828 (2021) 
787 0 |n https://www.mdpi.com/2076-3921/10/11/1828 
787 0 |n https://doaj.org/toc/2076-3921 
856 4 1 |u https://doaj.org/article/b2ff742f5df44003bbfc475b14a2710c  |z Connect to this object online.