Pre-treatment with the synthetic antioxidant T-butyl bisphenol protects cerebral tissues from experimental ischemia reperfusion injury.
Treatments to inhibit or repair neuronal cell damage sustained during focal ischemia/reperfusion injury in stroke are largely unavailable. We demonstrate that dietary supplementation with the antioxidant di-tert-butyl-bisphenol (BP) before injury decreases infarction and vascular complications in experimental stroke in an animal model. We confirm that BP, a synthetic polyphenol with superior radical-scavenging activity than vitamin E, crosses the blood-brain barrier and accumulates in rat brain. Supplementation with BP did not affect blood pressure or endogenous vitamin E levels in plasma or cerebral tissue. Pre-treatment with BP significantly lowered lipid, protein and thiol oxidation and decreased infarct size in animals subjected to middle cerebral artery occlusion (2 h) and reperfusion (24 h) injury. This neuroprotective action was accompanied by down-regulation of hypoxia inducible factor-1α and glucose transporter-1 mRNA levels, maintenance of neuronal tissue ATP concentration and inhibition of pro-apoptotic factors that together enhanced cerebral tissue viability after injury. That pre-treatment with BP ameliorates oxidative damage and preserves cerebral tissue during focal ischemic insult indicates that oxidative stress plays at least some causal role in promoting tissue damage in experimental stroke. The data strongly suggest that inhibition of oxidative stress through BP scavenging free radicals in vivo contributes significantly to neuroprotection. We demonstrate that pre-treatment with ditert-butyl bisphenol(Di-t-Bu-BP) inhibits lipid, protein, and total thiol oxidation and decreases caspase activation and infarct size in rats subjected to middle cerebral artery occlusion (2 h) and reperfusion (24 h) injury. These data suggest that inhibition of oxidative stress contributes significantly to neuroprotection.
Vascular Biology Group, ANZAC Research Institute, Concord Hospital, Concord, NSW, Australia.
Thi Thuy Hong
TT
Duong
Belal
B
Chami
Aisling C
AC
McMahon
Genevieve M
GM
Fong
Joanne M
JM
Dennis
Saul B
SB
Freedman
Paul K
PK
Witting
D000210:Acute-Phase Reaction / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D004032:Diet; D004591:Electrophoresis, Polyacrylamide Gel; D004734:Energy Metabolism / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000517:prevention & control; D008297:Male; D018696:Neuroprotective Agents; D010084:Oxidation-Reduction; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D020521:Stroke / Q000473:pathology; D013438:Sulfhydryl Compounds / Q000378:metabolism; D001713:Biphenyl Compounds
D000255:Adenosine Triphosphate; D000975:Antioxidants; D001559:Benzhydryl Compounds; D053148:Caspase 3; D053179:Caspase 7; D018696:Neuroprotective Agents; D010636:Phenols; D013438:Sulfhydryl Compounds; C404203:4,4'-bis(2,6-di-tert-butylphenol); D001713:Biphenyl Compounds
antioxidant; apoptosis; neuroprotection; polyphenol; stroke