In which period of injury is resveratrol treatment effective: ischemia or reperfusion?
The periods of ischemia and reperfusion represent different characteristics by lack of oxygen and reoxygenation. The aim of this experimental spinal cord injury model was to investigate whether resveratrol has protective effects during ischemia or reperfusion and the mechanism of the protection by using N-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase. Rabbits were divided into seven groups according to the time of administration of resveratrol or L-NAME (RI and RR, resveratrol during ischemia or reperfusion; IL and RL, L-NAME during ischemia or reperfusion; RILR, resveratrol during ischemia and L-NAME during reperfusion; LIRR, L-NAME during ischemia and resveratrol during reperfusion; control group). After neurologic evaluation at the twenty-fourth hour of reperfusion, lumbar spinal cords were removed for electron microscopic evaluation, immunohistochemical staining for apoptosis, and malondialdehyde (MDA) and myeloperoxidase (MPO) measurements. The RILR group had the best functional recovery, with a mean 3.6 Tarlov score (P < 0.05), and showed near normal electron microscopic findings (scores of 7.6 +/- 0.9 for the control group and 3.9 +/- 2.9 for the RILR group, P < 0.05). MPO and MDA levels were decreased in all groups compared with the control group, but only the decrement in the RILR group reached statistical significance. Immunohistochemical analysis showed that the groups including resveratrol and L-NAME together had the best staining for apoptosis. Resveratrol exhibits important protection by means of neurologic outcome, histopathologic analysis, and biochemical analysis, especially when used in during ischemia followed by L-NAME administration during reperfusion. Also, resveratrol protects against apoptosis, especially when combined with L-NAME.
Ulus
A Tulga
AT
Cardiovascular Surgery Department, Türkiye Yüksek Ihtisas Hospital, Sihheye, Ankara, Turkey. uluss@yahoo.com
Turan
Nilüfer N
NN
Seren
Mustafa
M
Budak
Baran
B
Tütün
Ufuk
U
Yazicioğlu
Hija
H
Sürücü
Selçuk
S
Akar
Fatma
F
Katircioğlu
S Fehmi
SF
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006614:Hindlimb / Q000503:physiopathology; D007150:Immunohistochemistry; D019194:Ischemic Preconditioning / Q000009:adverse effects*; D008159:Lumbar Vertebrae / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology; D008315:Malondialdehyde / Q000378:metabolism; D008854:Microscopy, Electron; D009068:Movement / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D020127:Recovery of Function / Q000187:drug effects; D015424:Reperfusion / Q000009:adverse effects*; D015427:Reperfusion Injury / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D000077185:Resveratrol; D013119:Spinal Cord Injuries / Q000209:etiology / Q000517:prevention & control; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors; D016896:Treatment Outcome
D000975:Antioxidants; D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D013267:Stilbenes; D008315:Malondialdehyde; D009195:Peroxidase; D000077185:Resveratrol; D019331:NG-Nitroarginine Methyl Ester