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On the selectivity of superoxide dismutase mimetics and its importance in pharmacological studies
Open accessAbstract
The list of pathophysiological conditions associated with the overproduction of superoxide expands every day. Much of the knowledge compiled on the role of this radical in disease has been gathered using the native superoxide dismutase enzyme and, more recently, by the use of superoxide dismutase knockout models or transgenic models that overexpress the various isoforms of the enzyme. Although the native enzyme has shown promising anti‐inflammatory properties in both preclinical and clinical studies, there were drawbacks and issues associated with its use as a therapeutic agent and pharmacological tool. Based on the concept that removal of superoxide modulates the course of inflammation, synthetic, low‐molecular‐weight mimetics of the superoxide dismutase enzymes that could overcome some of the limitations associated with the use of the native enzyme have been designed. In this review, we will discuss the advances made using various superoxide dismutase mimetics that led to the proposal that superoxide (and/or the product of its interaction with nitric oxide, peroxynitrite) is an important mediator of inflammation, and to the conclusion that superoxide dismutase mimetics can be utilized as therapeutic agents in diseases of various etiologies. The importance of the selectivity of such compounds in pharmacological studies will be discussed. British Journal of Pharmacology (2003) 140 , 445–460. doi: 10.1038/sj.bjp.0705430
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“A corollary of such considerations is that to decrease the amount of damage caused by OH• (or any other) radicals we need both to decrease their production and increase their removal to harmless substances [2141]”
From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [2141]
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Metadata
- Authors
- Muscoli, C., Cuzzocrea, S., Riley, D. P., Zweier, J. L., Thiemermann, C., Wang, Z., & Salvemini, D.
- Affiliations
- Magna Graecia University (IT)
- University of Messina (IT)
- The Ohio State University (US)
- William Harvey Research Institute (GB)
- Corresponding author
- Salvemini, Daniela
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2003-10
- Volume
- 140
- Issue
- 3
- Pages
- 445-460
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC1574047
- OpenAlex
- W2095342832
- Cited by
- 271
- References
- 217
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 10 · 2023: 7 · 2022: 6 · 2021: 12 · 2020: 6 · 2019: 11 · 2018: 13 · 2017: 11 · 2016: 11 · 2015: 7 · 2014: 12 · 2013: 14 · 2012: 19
- FWCI
- 0.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Keywords
- superoxide dismutase mimetic, superoxide, peroxynitrite, nitric oxide, inflammation, anti-inflammatory therapy, enzyme selectivity, superoxide dismutase isoforms, reactive oxygen species
- MeSH terms
- Animals, Humans, Superoxide Dismutase, Drug Delivery Systems, Biomimetic Materials
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