Reactive oxygen species plasmatic levels in ischemic stroke.
Oxidative stress is probably one of the mechanisms involved in neuronal damage induced by ischemia-reperfusion, and the antioxidant activity of plasma may be an important factor providing protection from neurological damage caused by stroke-associated oxidative stress. The aim of this study was to investigate the status of oxidative stress, NO and ONOO(-) levels in patients with atherothrombotic and lacunar acute ischemic stroke and iNOS, eNOS and nitrotyrosine expression in the same patients. Plasma ONOO(-) levels were significantly higher in patients than in controls while NO decreases in patients in respect to controls. Densitometric analysis of bands indicated that iNOS and N-Tyr protein levels were significantly higher in patients in respect to controls. This study has highlighted a significant NO decrease in our patients compared with controls and this is most probably due to the increased expression of inducible NO synthase by the effect of thrombotic attack. In fact, the constitutive NO isoforms, which produce small amounts of NO, are beneficial, while activation of the inducible isoform of NO, which produces much more NO, causes injury, being its toxicity greatly enhanced by generation of peroxynitrite. The significant ONOO(-) increase observed in our patients, compared to controls, is most probably due to reaction of NO with O(2)(*-) . These findings suggest that free radical production and oxidative stress in ischemic stroke might have a major role in the pathogenesis of ischemic brain injury. Peroxynitrite might be the main marker of brain damage and neurological impairment in acute ischemic stroke.
Nanetti
Laura
L
Institute of Biochemistry, Università Politecnica delle Marche, Ancona, Italy.
Taffi
Ruja
R
Vignini
Arianna
A
Moroni
Cinzia
C
Raffaelli
Francesca
F
Bacchetti
Tiziana
T
Silvestrini
Mauro
M
Provinciali
Leandro
L
Mazzanti
Laura
L
D000368:Aged; D050197:Atherosclerosis / Q000097:blood*; D002545:Brain Ischemia / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000097:blood; D052250:Nitric Oxide Synthase Type III / Q000097:blood; D018384:Oxidative Stress; D030421:Peroxynitrous Acid / Q000097:blood*; D017382:Reactive Oxygen Species / Q000097:blood*; D013927:Thrombosis / Q000097:blood*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D017382:Reactive Oxygen Species; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; C496314:NOS3 protein, human; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III