Role of nitroso radicals as drug targets in circulatory shock.
A vast amount of circumstantial evidence implicates oxygen-derived free radicals (especially, superoxide and hydroxyl radical) and high-energy oxidants [such as peroxynitrite (OONO(-))] as mediators of shock and ischaemia/reperfusion injury. Reactive oxygen species can initiate a wide range of toxic oxidative reactions. These include initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3 phosphate dehydrogenase, inhibition of membrane sodium/potassium adenosine 5'-triphosphate-ase activity, inactivation of membrane sodium channels and other oxidative modifications of proteins. All these toxicities are likely to play a role in the pathophysiology of shock and ischaemia and reperfusion. Moreover, various studies have clearly shown that treatment with either OONO(-) decomposition catalysts, which selectively inhibit OONO(-), or with superoxide dismutase (SOD) mimetics, which selectively mimic the catalytic activity of the human SOD enzymes, have been shown to prevent in vivo the delayed vascular decompensation and the cellular energetic failure associated with shock and ischaemia/reperfusion injury.
Esposito
Emanuela
E
IRCCS Centro Neurolesi Bonino-Pulejo, Messina, Italy.
Cuzzocrea
Salvatore
S
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D006801:Humans; D008665:Metalloporphyrins / Q000627:therapeutic use; D008954:Models, Biological; D015394:Molecular Structure; D026361:Reactive Nitrogen Species / Q000037:antagonists & inhibitors* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D012770:Shock, Cardiogenic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use
D000975:Antioxidants; D008665:Metalloporphyrins; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase