Cerebrovascular protection by various nitric oxide donors in rats after experimental stroke.
The efficacy of nitric oxide (NO) treatment in ischemic stroke, though well recognized, is yet to be tested in clinic. NO donors used to treat ischemic injury are structurally diverse compounds. We have shown that treatment of S-nitrosoglutathione (GSNO) protects the brain against injury and inflammation in rats after experimental stroke [M. Khan, B. Sekhon, S. Giri, M. Jatana, A. G. Gilg, K. Ayasolla, C. Elango, A. K. Singh, I. Singh, S-Nitrosoglutathione reduces inflammation and protects brain against focal cerebral ischemia in a rat model of experimental stroke, J. Cereb. Blood Flow Metab. 25 (2005) 177-192.]. In this study, we tested structurally different NO donors including GSNO, S-nitroso-N-acetyl-penicillamine (SNAP), sodium nitroprusside (SNP), methylamine hexamethylene methylamine NONOate (MAHMA), propylamine propylamine NONOate (PAPA), 3-morpholinosydnonimine (SIN-1) and compared their neuroprotective efficacy and antioxidant property in rats after ischemia/reperfusion (I/R). GSNO, in addition to neuroprotection, decreased nitrotyrosine formation and lipid peroxidation in blood and increased the ratio of reduced versus oxidized glutathione (GSH/GSSG) in brain as compared to untreated animals. GSNO also prevented the I/R-induced increase in mRNA expression of ICAM-1 and E-Selectin. SNAP and SNP extended limited neuroprotection, reduced nitrotyrosine formation in blood and blocked increase in mRNA expression of ICAM-1 and E-Selectin in brain tissue. PAPA, MAHMA, and SIN-1 neither protected the brain nor reduced oxidative stress. We conclude that neuroprotective action of NO donors in experimental stroke depends on their ability to reduce oxidative stress both in brain and blood.
Khan
Mushfiquddin
M
Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA.
Jatana
Manu
M
Elango
Chinnasamy
C
Paintlia
Ajaib Singh
AS
Singh
Avtar K
AK
Singh
Inderjit
I
D000818:Animals; D001923:Brain Chemistry; D002545:Brain Ischemia / Q000517:prevention & control*; D005978:Glutathione / Q000032:analysis; D019803:Glutathione Disulfide / Q000032:analysis; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000097:blood; D009569:Nitric Oxide / Q000032:analysis; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism
D008055:Lipids; D020030:Nitric Oxide Donors; D020011:Protective Agents; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D005978:Glutathione; D019803:Glutathione Disulfide