The antioxidant EPC-K1 ameliorates brain injury by inhibiting lipid peroxidation in a rat model of transient focal cerebral ischaemia.
BACKGROUND
Cerebral ischaemia-reperfusion injury is associated with the generation of reactive oxygen species during the early phases of reoxygenation. EPC-K1, a phosphate diester of vitamins C and E, has been reported to possess potent hydroxyl radical scavenging activity. This study was performed to investigate the effectiveness of EPC-K1 in attenuating cerebral ischaemia-reperfusion injury in a rat model of transient focal cerebral ischaemia.


METHODS
We evaluated the efficacy of EPC-K1 by measuring the concentration of cerebral thiobarbituric acid reactive substances (TBARS), an indicator of the extent of lipid peroxidation by free radicals, and infarct size in rats subjected to one hour of cerebral ischaemia and 4, 24, or 72 hours of reperfusion.


RESULTS
EPC-K1 significantly reduced both the cerebral TBARS level and the infarct size in a rat model of transient focal cerebral ischaemia. These results indicate that EPC-K1 administration during the early stages of reperfusion ameliorates ischaemic brain injury by inhibiting lipid peroxidation.


CONCLUSIONS
This report is the first to describe the protective mechanism of EPC-K1 by measuring both the TBARS level and infarct size in a rat model of transient focal cerebral ischaemia, and may suggest a potential clinical approach for the treatment of ischaemic cerebrovascular disease.
Kato
N
N
Department of Neurosurgery, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Yanaka
K
K
Nagase
S
S
Hirayama
A
A
Nose
T
T
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D005609:Free Radicals; D015227:Lipid Peroxidation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000975:Antioxidants; D005609:Free Radicals; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; C066638:potassium ascorbyl tocopheryl phosphate; D001205:Ascorbic Acid