Attenuation of oxidative DNA damage with a novel antioxidant EPC-K1 in rat brain neuronal cells after transient middle cerebral artery occlusion.
EPC-K1, L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl-hydrogen phosphate] potassium salt, is a novel antioxidant. In this study, we investigated a reduction of oxidative neuronal cell damage with EPC-K1 by immunohistochemical analysis for 8-hydroxy-2'-deoxyguanosine (8-OHdG) in rat brain with 60 min transient middle cerebral artery occlusion, in association with terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) and staining for total and active caspase-3. Treatment with EPC-K1 (20 mg kg(-1) i.v.) significantly reduced infarct size (p < 0.05) at 24 h of reperfusion. There were no positive cells for 8-OHdG and TUNEL in sham-operated brain, but numerous cells became positive for 8-OHdG, TUNEL and caspase-3 in the brains with ischemia. The number was markedly reduced in the EPC-K1 treated group. These reductions were particularly evident in the border zone of the infarct area, but the degree of reduction was less in caspase-3 staining than in 8-OHdG and TUNEL stainings. These results indicate EPC-K1 attenuates oxidative neuronal cell damage and prevents neuronal cell death.
Zhang
W R
WR
Department of Neurology, Okayama University School of Medicine and Dentistry, Japan. zhang@cc.okayama-u.ac.jp
Hayashi
T
T
Sasaki
C
C
Sato
K
K
Nagano
I
I
Manabe
Y
Y
Abe
K
K
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D020520:Brain Infarction / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects* / Q000502:physiology; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005609:Free Radicals / Q000037:antagonists & inhibitors / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000975:Antioxidants; D005609:Free Radicals; D018696:Neuroprotective Agents; D014810:Vitamin E; C066638:potassium ascorbyl tocopheryl phosphate; D000080242:8-Hydroxy-2'-Deoxyguanosine; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D003849:Deoxyguanosine; D001205:Ascorbic Acid