Dual Acting Carbon Monoxide Releasing Molecules and Carbonic Anhydrase Inhibitors Differentially Modulate Inflammation in Human Tenocytes

Sustained oxidative stress and inflammation have been reported as the major factors responsible for the failure of tendon healing during rotator cuff tears (RCTs) and rotator cuff disease (RCD). Although, their therapeutic management remains still challenging. Carbonic anhydrases (CAs) are involved...
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Gespeichert in:

Autor*in:	Marialucia Gallorini [verfasserIn] Anna C. Berardi [verfasserIn] Alessia Ricci [verfasserIn] Cristina Antonetti Lamorgese Passeri [verfasserIn] Susi Zara [verfasserIn] Francesco Oliva [verfasserIn] Amelia Cataldi [verfasserIn] Fabrizio Carta [verfasserIn] Simone Carradori [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	tendons inflammation rotator cuff Nrf2 iNOS carbonic anhydrase

Übergeordnetes Werk:	In: Biomedicines - MDPI AG, 2014, 9(2021), 2, p 141
Übergeordnetes Werk:	volume:9 ; year:2021 ; number:2, p 141

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/biomedicines9020141

Katalog-ID:	DOAJ056475195

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spelling	10.3390/biomedicines9020141 doi (DE-627)DOAJ056475195 (DE-599)DOAJ05baa699e59a40bb90734ebb850c8abd DE-627 ger DE-627 rakwb eng QH301-705.5 Marialucia Gallorini verfasserin aut Dual Acting Carbon Monoxide Releasing Molecules and Carbonic Anhydrase Inhibitors Differentially Modulate Inflammation in Human Tenocytes 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Sustained oxidative stress and inflammation have been reported as the major factors responsible for the failure of tendon healing during rotator cuff tears (RCTs) and rotator cuff disease (RCD). Although, their therapeutic management remains still challenging. Carbonic anhydrases (CAs) are involved in many pathological conditions, and the overexpression of both CA9 and 12 in inflamed joints has been recently reported. Consequently, a selective CA9/12 inhibition could be a feasible strategy for improving tendon recovery after injury. In addition, since carbon monoxide (CO) has been proven to have an important role in modulating inflammation, CO releasing molecules (CORMs) can be also potentially suitable compounds. The present study aims at evaluating five newly synthesized dual-mode acting CA inhibitors (CAIs)-CORMs compounds, belonging to two chemical scaffolds, on tendon-derived human primary cells under H<sub<2</sub<O<sub<2</sub< stimulation in comparison with Meloxicam. Our results show that compounds <b<2</b< and <b<7</b< are the most promising of the series in counteracting oxidative stress-induced cytotoxicity and display a better profile in terms of enhanced viability, decreased LDH release, and augmented tenocyte proliferation compared to Meloxicam. Moreover, compound <b<7</b<, as a potent superoxide scavenger, exerts its action inhibiting NF-ĸB translocation and downregulating iNOS, whereas compound <b<2</b< is more effective in increasing collagen I deposition. Taken together, our data highlight a potential role of CA in RCTs and RCD and the prospective effectiveness of compounds acting as CAI-CORM during inflammation. tendons inflammation rotator cuff Nrf2 iNOS carbonic anhydrase Biology (General) Anna C. Berardi verfasserin aut Alessia Ricci verfasserin aut Cristina Antonetti Lamorgese Passeri verfasserin aut Susi Zara verfasserin aut Francesco Oliva verfasserin aut Amelia Cataldi verfasserin aut Fabrizio Carta verfasserin aut Simone Carradori verfasserin aut In Biomedicines MDPI AG, 2014 9(2021), 2, p 141 (DE-627)750370483 (DE-600)2720867-9 22279059 nnns volume:9 year:2021 number:2, p 141 https://doi.org/10.3390/biomedicines9020141 kostenfrei https://doaj.org/article/05baa699e59a40bb90734ebb850c8abd kostenfrei https://www.mdpi.com/2227-9059/9/2/141 kostenfrei https://doaj.org/toc/2227-9059 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2021 2, p 141
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author	Marialucia Gallorini
spellingShingle	Marialucia Gallorini misc QH301-705.5 misc tendons misc inflammation misc rotator cuff misc Nrf2 misc iNOS misc carbonic anhydrase misc Biology (General) Dual Acting Carbon Monoxide Releasing Molecules and Carbonic Anhydrase Inhibitors Differentially Modulate Inflammation in Human Tenocytes
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topic_title	QH301-705.5 Dual Acting Carbon Monoxide Releasing Molecules and Carbonic Anhydrase Inhibitors Differentially Modulate Inflammation in Human Tenocytes tendons inflammation rotator cuff Nrf2 iNOS carbonic anhydrase
topic	misc QH301-705.5 misc tendons misc inflammation misc rotator cuff misc Nrf2 misc iNOS misc carbonic anhydrase misc Biology (General)
topic_unstemmed	misc QH301-705.5 misc tendons misc inflammation misc rotator cuff misc Nrf2 misc iNOS misc carbonic anhydrase misc Biology (General)
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title	Dual Acting Carbon Monoxide Releasing Molecules and Carbonic Anhydrase Inhibitors Differentially Modulate Inflammation in Human Tenocytes
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title_full	Dual Acting Carbon Monoxide Releasing Molecules and Carbonic Anhydrase Inhibitors Differentially Modulate Inflammation in Human Tenocytes
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title_sort	dual acting carbon monoxide releasing molecules and carbonic anhydrase inhibitors differentially modulate inflammation in human tenocytes
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title_auth	Dual Acting Carbon Monoxide Releasing Molecules and Carbonic Anhydrase Inhibitors Differentially Modulate Inflammation in Human Tenocytes
abstract	Sustained oxidative stress and inflammation have been reported as the major factors responsible for the failure of tendon healing during rotator cuff tears (RCTs) and rotator cuff disease (RCD). Although, their therapeutic management remains still challenging. Carbonic anhydrases (CAs) are involved in many pathological conditions, and the overexpression of both CA9 and 12 in inflamed joints has been recently reported. Consequently, a selective CA9/12 inhibition could be a feasible strategy for improving tendon recovery after injury. In addition, since carbon monoxide (CO) has been proven to have an important role in modulating inflammation, CO releasing molecules (CORMs) can be also potentially suitable compounds. The present study aims at evaluating five newly synthesized dual-mode acting CA inhibitors (CAIs)-CORMs compounds, belonging to two chemical scaffolds, on tendon-derived human primary cells under H<sub<2</sub<O<sub<2</sub< stimulation in comparison with Meloxicam. Our results show that compounds <b<2</b< and <b<7</b< are the most promising of the series in counteracting oxidative stress-induced cytotoxicity and display a better profile in terms of enhanced viability, decreased LDH release, and augmented tenocyte proliferation compared to Meloxicam. Moreover, compound <b<7</b<, as a potent superoxide scavenger, exerts its action inhibiting NF-ĸB translocation and downregulating iNOS, whereas compound <b<2</b< is more effective in increasing collagen I deposition. Taken together, our data highlight a potential role of CA in RCTs and RCD and the prospective effectiveness of compounds acting as CAI-CORM during inflammation.
abstractGer	Sustained oxidative stress and inflammation have been reported as the major factors responsible for the failure of tendon healing during rotator cuff tears (RCTs) and rotator cuff disease (RCD). Although, their therapeutic management remains still challenging. Carbonic anhydrases (CAs) are involved in many pathological conditions, and the overexpression of both CA9 and 12 in inflamed joints has been recently reported. Consequently, a selective CA9/12 inhibition could be a feasible strategy for improving tendon recovery after injury. In addition, since carbon monoxide (CO) has been proven to have an important role in modulating inflammation, CO releasing molecules (CORMs) can be also potentially suitable compounds. The present study aims at evaluating five newly synthesized dual-mode acting CA inhibitors (CAIs)-CORMs compounds, belonging to two chemical scaffolds, on tendon-derived human primary cells under H<sub<2</sub<O<sub<2</sub< stimulation in comparison with Meloxicam. Our results show that compounds <b<2</b< and <b<7</b< are the most promising of the series in counteracting oxidative stress-induced cytotoxicity and display a better profile in terms of enhanced viability, decreased LDH release, and augmented tenocyte proliferation compared to Meloxicam. Moreover, compound <b<7</b<, as a potent superoxide scavenger, exerts its action inhibiting NF-ĸB translocation and downregulating iNOS, whereas compound <b<2</b< is more effective in increasing collagen I deposition. Taken together, our data highlight a potential role of CA in RCTs and RCD and the prospective effectiveness of compounds acting as CAI-CORM during inflammation.
abstract_unstemmed	Sustained oxidative stress and inflammation have been reported as the major factors responsible for the failure of tendon healing during rotator cuff tears (RCTs) and rotator cuff disease (RCD). Although, their therapeutic management remains still challenging. Carbonic anhydrases (CAs) are involved in many pathological conditions, and the overexpression of both CA9 and 12 in inflamed joints has been recently reported. Consequently, a selective CA9/12 inhibition could be a feasible strategy for improving tendon recovery after injury. In addition, since carbon monoxide (CO) has been proven to have an important role in modulating inflammation, CO releasing molecules (CORMs) can be also potentially suitable compounds. The present study aims at evaluating five newly synthesized dual-mode acting CA inhibitors (CAIs)-CORMs compounds, belonging to two chemical scaffolds, on tendon-derived human primary cells under H<sub<2</sub<O<sub<2</sub< stimulation in comparison with Meloxicam. Our results show that compounds <b<2</b< and <b<7</b< are the most promising of the series in counteracting oxidative stress-induced cytotoxicity and display a better profile in terms of enhanced viability, decreased LDH release, and augmented tenocyte proliferation compared to Meloxicam. Moreover, compound <b<7</b<, as a potent superoxide scavenger, exerts its action inhibiting NF-ĸB translocation and downregulating iNOS, whereas compound <b<2</b< is more effective in increasing collagen I deposition. Taken together, our data highlight a potential role of CA in RCTs and RCD and the prospective effectiveness of compounds acting as CAI-CORM during inflammation.
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title_short	Dual Acting Carbon Monoxide Releasing Molecules and Carbonic Anhydrase Inhibitors Differentially Modulate Inflammation in Human Tenocytes
url	https://doi.org/10.3390/biomedicines9020141 https://doaj.org/article/05baa699e59a40bb90734ebb850c8abd https://www.mdpi.com/2227-9059/9/2/141 https://doaj.org/toc/2227-9059
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Our results show that compounds <b<2</b< and <b<7</b< are the most promising of the series in counteracting oxidative stress-induced cytotoxicity and display a better profile in terms of enhanced viability, decreased LDH release, and augmented tenocyte proliferation compared to Meloxicam. Moreover, compound <b<7</b<, as a potent superoxide scavenger, exerts its action inhibiting NF-ĸB translocation and downregulating iNOS, whereas compound <b<2</b< is more effective in increasing collagen I deposition. 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Dual Acting Carbon Monoxide Releasing Molecules and Carbonic Anhydrase Inhibitors Differentially Modulate Inflammation in Human Tenocytes

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