Protective Effect of Antioxidants in Nitric Oxide/COX-2 Interaction during Inflammatory Pain: The Role of Nitration

Autor: D. Ventrice, Valentina Malafoglia, Sara Ilari, Stefania Proietti, Fiorella Guadagni, Daniela Salvemini, Luigino Antonio Giancotti, Milena Rizzo, Ernesto Palma, Carolina Muscoli, Filomena Lauro, Micaela Gliozzi, Vincenzo Mollace, Antonella Spila, Concetta Dagostino
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Antioxidants, Vol 9, Iss 1284, p 1284 (2020)
Antioxidants
Volume 9
Issue 12
ISSN: 2076-3921
Popis: 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 PGE2 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 PGE2 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 PGE2 levels, and blocked the development of thermal hyperalgesia.
Databáze: OpenAIRE