Lecithinized superoxide dismutase improves outcomes and attenuates focal cerebral ischemic injury via antiapoptotic mechanisms in rats.
OBJECTIVE
Recent studies have shown the antiapoptotic neuroprotective effects of lecithinized superoxide dismutase (PC-SOD) in different forms of brain injury. We tested the effects of PC-SOD in focal cerebral ischemia in the rat middle cerebral artery occlusion model (MCAO).


METHODS
Adult male Sprague-Dawley rats were treated with PC-SOD (0.3, 1.0, and 3.0 mg/kg) administered intravenously after 90 minutes of occlusion (beginning of reperfusion). Physiological parameters, neurological score, and infarct volume were assessed at 24 and 72 hours in 3 groups of animals: sham-operated (n=18), MCAO treated with vehicle (n=26), and MCAO treated with PC-SOD (n=37). Oxidative stress was evaluated by malondialdehyde assay, and the apoptotic mechanisms were studied by Western blotting.


RESULTS
PC-SOD treatment significantly reduced infarct volume and improved neurological scores at different time points compared with the vehicle-treated group. PC-SOD treatment decreased malondialdehyde levels, cytochrome c, and cleaved caspase 3 expression and increased mitochondrial Bcl-2 expression.


CONCLUSIONS
Inhibition of oxidative stress with PC-SOD treatment improves outcomes after focal cerebral ischemia. This neuroprotective effect is likely exerted by antiapoptotic mechanisms.
Tsubokawa
Tamiji
T
Department of Physiology, Loma Linda University Medical Center, Loma Linda, CA 92354, USA.
Jadhav
Vikram
V
Solaroglu
Ihsan
I
Shiokawa
Yoshiaki
Y
Konishi
Yoshifumi
Y
Zhang
John H
JH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010713:Phosphatidylcholines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D010713:Phosphatidylcholines; D011994:Recombinant Proteins; D013482:Superoxide Dismutase; C434045:lecithinized superoxide dismutase