Protective Effect of Antioxidants in Nitric Oxide/COX-2 Interaction during Inflammatory Pain: The Role of Nitration
In clinical practice, inflammatory pain is an important, unresolved health problem, despite the utilization of non-steroidal anti-inflammatory drugs (NSAIDs). In the last decade, different studies have proven that reactive oxygen species (ROS) and reactive nitrogen species (RNS) are involved in the...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/12/1284 |
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| author | Sara Ilari Concetta Dagostino Valentina Malafoglia Filomena Lauro Luigino Antonio Giancotti Antonella Spila Stefania Proietti Domenica Ventrice Milena Rizzo Micaela Gliozzi Ernesto Palma Fiorella Guadagni Daniela Salvemini Vincenzo Mollace Carolina Muscoli |
| author_facet | Sara Ilari Concetta Dagostino Valentina Malafoglia Filomena Lauro Luigino Antonio Giancotti Antonella Spila Stefania Proietti Domenica Ventrice Milena Rizzo Micaela Gliozzi Ernesto Palma Fiorella Guadagni Daniela Salvemini Vincenzo Mollace Carolina Muscoli |
| author_sort | Sara Ilari |
| collection | DOAJ |
| description | In clinical practice, inflammatory pain is an important, unresolved health problem, despite the utilization of non-steroidal anti-inflammatory drugs (NSAIDs). In the last decade, different studies have proven that reactive oxygen species (ROS) and reactive nitrogen species (RNS) are involved in the development and maintenance of inflammatory pain and hyperalgesia via the post-translation modification of key proteins, such as manganese superoxide dismutase (MnSOD). It is well-known that inducible cyclooxygenase 2 (COX-2) plays a crucial role at the beginning of the inflammatory response by converting arachidonic acid into proinflammatory prostaglandin PGE<sub>2</sub> and then producing other proinflammatory chemokines and cytokines. Here, we investigated the impact of oxidative stress on COX-2 and prostaglandin (PG) pathways in paw exudates, and we studied how this mechanism can be reversed by using antioxidants during hyperalgesia in a well-characterized model of inflammatory pain in rats. Our results reveal that during the inflammatory state, induced by intraplantar administration of carrageenan, the increase of PGE<sub>2</sub> levels released in the paw exudates were associated with COX-2 nitration. Moreover, we showed that the inhibition of ROS with Mn (III) tetrakis (4-benzoic acid) porphyrin(MnTBAP) antioxidant prevented COX-2 nitration, restored the PGE<sub>2</sub> levels, and blocked the development of thermal hyperalgesia. |
| first_indexed | 2024-03-10T14:03:14Z |
| format | Article |
| id | doaj.art-b42f5487aaff4d0db40ad2b1d198e625 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T14:03:14Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-b42f5487aaff4d0db40ad2b1d198e6252023-11-21T00:59:03ZengMDPI AGAntioxidants2076-39212020-12-01912128410.3390/antiox9121284Protective Effect of Antioxidants in Nitric Oxide/COX-2 Interaction during Inflammatory Pain: The Role of NitrationSara Ilari0Concetta Dagostino1Valentina Malafoglia2Filomena Lauro3Luigino Antonio Giancotti4Antonella Spila5Stefania Proietti6Domenica Ventrice7Milena Rizzo8Micaela Gliozzi9Ernesto Palma10Fiorella Guadagni11Daniela Salvemini12Vincenzo Mollace13Carolina Muscoli14Institute of Research for Food Safety & Health (IRC-FSH), Department of Health Science, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, ItalyInstitute of Research for Food Safety & Health (IRC-FSH), Department of Health Science, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, ItalyInstitute for Research on Pain, ISAL Foundation, 47922 Torre Pedrera, ItalyDepartment of Pharmacology and Physiology, Henry and Amelia Nasrallah Center for Neuroscience, Saint Louis University School of Medicine, St. Louis, MO 63104, USADepartment of Pharmacology and Physiology, Henry and Amelia Nasrallah Center for Neuroscience, Saint Louis University School of Medicine, St. Louis, MO 63104, USADepartment of Human Science & Quality of Life Promotion, San Raffaele Roma Open University, via di Val Cannuta 247, 0166 Rome, ItalyScientific Direction, IRCCS San Raffaele Pisana, via di Val Cannuta 247, 0166 Rome, ItalyARPACAL, 88100 Catanzaro, ItalyDepartment of Drug Science, University of Catania, Viale Andrea Doria 6, 95125 Catania, ItalyInstitute of Research for Food Safety & Health (IRC-FSH), Department of Health Science, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, ItalyInstitute of Research for Food Safety & Health (IRC-FSH), Department of Health Science, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, ItalyDepartment of Human Science & Quality of Life Promotion, SanRaffaele Roma Open University, and Inter-Institutional Multidisciplinary BioBank (BioBIM), IRCCS San Raffaele Pisana, via di Val Cannuta 247, 0166 Rome, ItalyDepartment of Pharmacology and Physiology, Henry and Amelia Nasrallah Center for Neuroscience, Saint Louis University School of Medicine, St. Louis, MO 63104, USAInstitute of Research for Food Safety & Health (IRC-FSH), Department of Health Science, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, ItalyInstitute of Research for Food Safety & Health (IRC-FSH), Department of Health Science, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, ItalyIn clinical practice, inflammatory pain is an important, unresolved health problem, despite the utilization of non-steroidal anti-inflammatory drugs (NSAIDs). In the last decade, different studies have proven that reactive oxygen species (ROS) and reactive nitrogen species (RNS) are involved in the development and maintenance of inflammatory pain and hyperalgesia via the post-translation modification of key proteins, such as manganese superoxide dismutase (MnSOD). It is well-known that inducible cyclooxygenase 2 (COX-2) plays a crucial role at the beginning of the inflammatory response by converting arachidonic acid into proinflammatory prostaglandin PGE<sub>2</sub> and then producing other proinflammatory chemokines and cytokines. Here, we investigated the impact of oxidative stress on COX-2 and prostaglandin (PG) pathways in paw exudates, and we studied how this mechanism can be reversed by using antioxidants during hyperalgesia in a well-characterized model of inflammatory pain in rats. Our results reveal that during the inflammatory state, induced by intraplantar administration of carrageenan, the increase of PGE<sub>2</sub> levels released in the paw exudates were associated with COX-2 nitration. Moreover, we showed that the inhibition of ROS with Mn (III) tetrakis (4-benzoic acid) porphyrin(MnTBAP) antioxidant prevented COX-2 nitration, restored the PGE<sub>2</sub> levels, and blocked the development of thermal hyperalgesia.https://www.mdpi.com/2076-3921/9/12/1284inflammationcyclooxygenase 2 (COX-2)prostaglandin E<sub>2</sub> (PGE<sub>2</sub>)lactate dehydrogenase (LDH)nitrationmalondialdehyde (MDA) |
| spellingShingle | Sara Ilari Concetta Dagostino Valentina Malafoglia Filomena Lauro Luigino Antonio Giancotti Antonella Spila Stefania Proietti Domenica Ventrice Milena Rizzo Micaela Gliozzi Ernesto Palma Fiorella Guadagni Daniela Salvemini Vincenzo Mollace Carolina Muscoli Protective Effect of Antioxidants in Nitric Oxide/COX-2 Interaction during Inflammatory Pain: The Role of Nitration Antioxidants inflammation cyclooxygenase 2 (COX-2) prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) lactate dehydrogenase (LDH) nitration malondialdehyde (MDA) |
| title | Protective Effect of Antioxidants in Nitric Oxide/COX-2 Interaction during Inflammatory Pain: The Role of Nitration |
| title_full | Protective Effect of Antioxidants in Nitric Oxide/COX-2 Interaction during Inflammatory Pain: The Role of Nitration |
| title_fullStr | Protective Effect of Antioxidants in Nitric Oxide/COX-2 Interaction during Inflammatory Pain: The Role of Nitration |
| title_full_unstemmed | Protective Effect of Antioxidants in Nitric Oxide/COX-2 Interaction during Inflammatory Pain: The Role of Nitration |
| title_short | Protective Effect of Antioxidants in Nitric Oxide/COX-2 Interaction during Inflammatory Pain: The Role of Nitration |
| title_sort | protective effect of antioxidants in nitric oxide cox 2 interaction during inflammatory pain the role of nitration |
| topic | inflammation cyclooxygenase 2 (COX-2) prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) lactate dehydrogenase (LDH) nitration malondialdehyde (MDA) |
| url | https://www.mdpi.com/2076-3921/9/12/1284 |
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