A Nonpeptidyl Mimic of Superoxide Dismutase with Therapeutic Activity in Rats

Many human diseases are associated with the overproduction of oxygen free radicals that inflict cell damage. A manganese(II) complex with a bis(cyclohexylpyridine)-substituted macrocyclic ligand (M40403) was designed to be a functional mimic of the superoxide dismutase (SOD) enzymes that normally re...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1999-10, Vol.286 (5438), p.304-306
Main Authors: Salvemini, Daniela, Wang, Zhi-Qiang, Zweier, Jay L., Samouilov, Alexandre, Macarthur, Heather, Misko, Thomas P., Currie, Mark G., Cuzzocrea, Salvatore, Sikorski, James A., Riley, Dennis P.
Format: Article
Language:English
Subjects:
Animal mimicry
Animals
Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal - chemistry
Anti-Inflammatory Agents, Non-Steroidal - metabolism
Anti-Inflammatory Agents, Non-Steroidal - therapeutic use
Biological and medical sciences
Bones, joints and connective tissue. Antiinflammatory agents
Cytoprotection
Dinoprostone - metabolism
Disease
Dose-Response Relationship, Drug
Drug Design
Drug Stability
Drug therapy
Edema
Enzymes
Free radicals
Health aspects
Inflammation
Inflammation - drug therapy
Inhibition
Injuries
Interleukin-1 - metabolism
L-Lactate Dehydrogenase - metabolism
Lungs
Male
Manganese
Medical sciences
Molecular Mimicry
Neutrophils
Neutrophils - drug effects
Organometallic Compounds - chemical synthesis
Organometallic Compounds - chemistry
Organometallic Compounds - metabolism
Organometallic Compounds - toxicity
Pharmacology
Pharmacology. Drug treatments
Physiological aspects
Rats
Rats, Sprague-Dawley
Reperfusion
Reperfusion injury
Reperfusion Injury - drug therapy
Rodents
Splanchnic Circulation
Superoxide
Superoxide dismutase
Superoxide Dismutase - metabolism
Superoxides
Superoxides - metabolism
Time Factors
Tumor Necrosis Factor-alpha - metabolism
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Summary:Many human diseases are associated with the overproduction of oxygen free radicals that inflict cell damage. A manganese(II) complex with a bis(cyclohexylpyridine)-substituted macrocyclic ligand (M40403) was designed to be a functional mimic of the superoxide dismutase (SOD) enzymes that normally remove these radicals. M40403 had high catalytic SOD activity and was chemically and biologically stable in vivo. Injection of M40403 into rat models of inflammation and ischemia-reperfusion injury protected the animals against tissue damage. Such mimics may result in better clinical therapies for diseases mediated by superoxide radicals.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.286.5438.304