Protective effect of antioxidants in nitric oxide/cox-2 interaction during inflammatory pain: The role of nitration

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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number1284
Pages (from-to)1-15
Number of pages15
Issue number12
Publication statusPublished - Dec 2020


  • Antioxidants
  • Cyclooxygenase 2 (COX-2)
  • Inflammation
  • Lactate dehydrogenase (LDH)
  • Malondialdehyde (MDA)
  • Nitration
  • Prostaglandin E (PGE)
  • Reactive nitrogen species (RNS)
  • Reactive oxygen species (ROS)

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology


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