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

Antioxidants

Domenica Ventrice¹  Milena Rizzo²  Antonella Spila³  Fiorella Guadagni⁴  Filomena Lauro⁵  Daniela Salvemini⁵  LuiginoAntonio Giancotti⁵  Valentina Malafoglia⁶  Micaela Gliozzi⁷  Sara Ilari⁷  Concetta Dagostino⁷  Ernesto Palma⁷  Carolina Muscoli⁷  Vincenzo Mollace⁷  Stefania Proietti⁸ 

[1] ARPACAL, 88100 Catanzaro, Italy;Department of Drug Science, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy;Department of Human Science & Quality of Life Promotion, San Raffaele Roma Open University, via di Val Cannuta 247, 0166 Rome, Italy;Department 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, Italy;Department of Pharmacology and Physiology, Henry and Amelia Nasrallah Center for Neuroscience, Saint Louis University School of Medicine, St. Louis, MO 63104, USA;Institute for Research on Pain, ISAL Foundation, 47922 Torre Pedrera, Italy;Institute of Research for Food Safety & Health (IRC-FSH), Department of Health Science, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy;Scientific Direction, IRCCS San Raffaele Pisana, via di Val Cannuta 247, 0166 Rome, Italy;

关键词: inflammation;    cyclooxygenase 2 (COX-2);    prostaglandin E₂ (PGE₂);    lactate dehydrogenase (LDH);    nitration;    malondialdehyde (MDA);   

DOI  :  10.3390/antiox9121284

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown