TEMPOL, a membrane-permeable radical scavenger, attenuates peroxynitrite- and superoxide anion-enhanced carrageenan-induced paw edema and hyperalgesia: A key role for superoxide anion
Abstract
Carrageenan produces both inflammation and pain when injected in rat paws via enhancement of the formation of reactive oxygen species. We have tested the effect of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL), a membrane-permeable superoxide dismutase (SOD) mimetic in carrageenan-induced rat paw edema. Treatment of rats with TEMPOL (15, 30, and 60 mg/kg, 15 min prior to carrageenan) inhibited the paw edema. Furthermore, treatment of rats with the SOD inhibitor diethylthiocarbamate (DETCA, 100 mg/kg, 1 h before carrageenan) enhanced the carrageenan-induced paw edema. Co-administration of peroxynitrite with carrageenan produced a similar fortification of the carrageenan-induced edema. Prior treatment of rats with TEMPOL (30 mg/kg) inhibited the enhancement produced by DETCA treatment (endogenous superoxide anion stress) as well as that produced by the peroxynitrite stress. The effect of TEMPOL as well as the influence of superoxide anion and peroxynitrite stresses was also tested in carrageenan-induced hyperalgesia model. Carrageenan (500 mug/paw) produced significant hyperalgesia presented as shortening of withdrawal latency times using hot plate (52 degrees C) starting 30 min after carrageenan and lasting for 3 h. TEMPOL (60 mg/kg, injected 15 min before carrageenan) ameliorated this hyperalgesia during the first 2 h. Concurrent administration of peroxynitrite promptly intensified the carrageenan hyperalgesia. TEMPOL (60 mg/kg, 15 min before peroxynitrite-carrageenan) inhibited the peroxynitrite enhancement of carrageenan hyperalgesia when tested at 60 min after injection of the cocktail. The present investigation gives the proof for the effectiveness of TEMPOL as anti-inflammation and analgesic agents in carrageenan-induced model of inflammation and hyperalgesia. It further indicated the importance of superoxide anion and peroxynitrite in acute inflammation and inflammatory pain. This raises the chances for considering pharmacologic interventions that interrupt superoxide anion and peroxynitrite stress for putative alternative agents as anti-inflammatory analgesic new medical strategies.
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The body is physiologically adept at transporting and storing larger concentrations of zinc with no risk of producing reactive oxygen species, unlike high concentrations of copper.
“Because of this, the body is physiologically adept at transporting and storing larger concentrations of zinc with no risk of producing reactive oxygen species, a consequence of high concentrations of copper and mediators of acute and chronic inflammatory pain (32,33).”
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- Authors
- Khattab, M. M.
- Affiliations
- King Saud University (SA)
- Corresponding author
- Khattab, Mahmoud M.
- ORCID
- Khattab, Mahmoud M.
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2006-10
- Volume
- 548
- Issue
- 1-3
- Pages
- 167-173
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W1970008312
- Cited by
- 122
- References
- 32
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 1 · 2023: 5 · 2022: 4 · 2021: 5 · 2020: 8 · 2019: 5 · 2018: 6 · 2017: 9 · 2016: 7 · 2015: 6 · 2014: 8 · 2013: 11 · 2012: 3
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- tempol, superoxide dismutase mimetic, peroxynitrite, superoxide, carrageenan-induced paw edema, inflammatory hyperalgesia, reactive oxygen species, anti-inflammatory agents, analgesics, oxidative stress, acute inflammation, inflammatory pain, hot plate test
- MeSH terms
- Animals, Anti-Inflammatory Agents, Carrageenan, Cyclic N-Oxides, Edema, Enzyme Inhibitors, Foot, Hot Temperature, Hyperalgesia, Male, Penicillamine, Pyrogallol, Spin Labels, Superoxides, Superoxide Dismutase, Thiocarbamates, Free Radical Scavengers, Rats, Wistar, Nitric Oxide Donors, Peroxynitrous Acid, Rats
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