Acute effects of 17beta-estradiol on oxidative stress in ischemic rat striatum.
Changes in the extracellular concentrations of monoamines, their metabolites, and hydrogen peroxide in the rat striatum during middle cerebral artery (MCA) occlusion and reperfusion were investigated by a microdialysis procedure, and the effects of 17beta-estradiol and tamoxifen (an antagonist of estrogen receptors) on them were evaluated. Male Wistar rats were randomly divided into four groups: saline-treated animals, 17beta-estradiol-treated animals, saline-plus-tamoxifen-treated animals, and 17beta-estradiol-plus-tamoxifen-treated animals. Sixty minutes after an intracerebroventricular injection of saline (20 microL) or 17beta-estradiol (150 microg/20 microL), all animals were subjected to 15-minute MCA occlusion under anesthesia. Tamoxifen (1.5 mg) or vehicle was intravenously administered 30 minutes before the saline or 17beta-estradiol treatment. Microdialysis samples in the striatum were collected every 15 minutes, and concentrations of monoamines, their metabolites, and hydrogen peroxide were determined. Delayed neuronal death in the striatal neurons was observed after 7 days by light microscopy. Administration of 17beta-estradiol reduced neuronal damage caused by focal ischemia. Tamoxifen did not affect the improvement by 17beta-estradiol. Although transient ischemia produced a marked increase in the dopamine level, there were no differences in the peak level among the groups. The level of hydrogen peroxide was increased after reperfusion in the saline group. The level in the 17beta-estradiol group was suppressed before induction of ischemia, and no increase was observed by ischemia. Tamoxifen did not affect the suppression of the increase by 17beta-estradiol. Acute treatment with 17beta-estradiol showed a protective effect against ischemia-reperfusion injury. Antioxidant effects of the agent may be a predominant mechanism underlying the protection.
Kii
Norikatsu
N
Department of Anesthesiology and Resuscitology, Ehime University School of Medicine, Ehime, Japan. keys@m.ehime-u.ac.jp
Adachi
Naoto
N
Liu
Keyue
K
Arai
Tatsuru
T
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D017072:Neostriatum / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D013629:Tamoxifen / Q000494:pharmacology
D015306:Biogenic Monoamines; D004965:Estrogen Antagonists; D013629:Tamoxifen; D004958:Estradiol; D006861:Hydrogen Peroxide