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Pre‐treatment with the synthetic antioxidant T‐butyl bisphenol protects cerebral tissues from experimental ischemia reperfusion injury
Author(s) -
Duong Thi Thuy Hong,
Chami Belal,
McMahon Aisling C.,
Fong Genevieve M.,
Dennis Joanne M.,
Freedman Saul B.,
Witting Paul K.
Publication year - 2014
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12747
Subject(s) - neuroprotection , oxidative stress , ischemia , pharmacology , vitamin e , antioxidant , reperfusion injury , stroke (engine) , medicine , vitamin c , chemistry , endocrinology , biochemistry , mechanical engineering , engineering
Abstract 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 di tert ‐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.