Metalloporphyrins as a therapeutic drug class against peroxynitrite in cardiovascular diseases involving ischemic reperfusion injury.
Peroxynitrite is well-recognized as being capable of inducing damaging cellular effects and has been identified as a mediator of cell damage in numerous disease states, including cardiovascular diseases. Metalloporphyrins are a class of molecule that represents an exciting new pharmacological approach to reducing peroxynitrite levels. These compounds catalyze the conversion of the harmful peroxynitrite molecules into less toxic derivatives and can be considered the reasonable intervention to reduce the toxicity of peroxynitrite. Several compounds have been synthesized and tested with promising results. Differences in the metalloporphyrin structure affect their reactivity. Iron-based metalloporphyrins display the highest rate of peroxynitrite decomposition with the narrowest scope of side reactions, whereas manganese-based metalloporphyrins react slower and with more pronounced secondary reactions, notably functioning as superoxide dismutase mimetics. This review examines the evidence that peroxynitrite is operative in patients with cardiovascular disease focusing on metalloporphyrin peroxynitrite decomposition catalysts and the evidence for their utility in the pharmacological treatment of major cardiovascular diseases. The data suggest that modification of peroxynitrite-induced cardiovascular injury is an intriguing and useful treatment approach.
Rabkin
Simon W
SW
Cardiovascular Medicine, University of British Columbia, Vancouver, B.C., Canada. rabkin@interchange.ubc.ca
Klassen
Shaun S
SS
D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D002384:Catalysis; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D008665:Metalloporphyrins / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D030421:Peroxynitrous Acid / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology
D016166:Free Radical Scavengers; D008665:Metalloporphyrins; D030421:Peroxynitrous Acid