Long-term melatonin or 17β-estradiol supplementation alleviates oxidative stress in ovariectomized adult
Long-term melatonin or 17β-estradiol supplementation alleviates oxidative stress in ovariectomized adult
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DOI：
10.1016/j.freeradbiomed.2005.03.007
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发表时间：
2005-07-15
影响因子：
7.4
通讯作者：
Zhang, JT
中科院分区：
文献类型：
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作者：
Feng, Z;Zhang, JT
褪黑激素是一种内源性产生的有效抗氧化剂。我们以前的研究结果表明，褪黑激素通过改善胆碱能神经系统功能障碍，防止细胞凋亡，改善阿尔茨海默病（AD）转基因小鼠模型和卵巢切除（OVX）大鼠的学习和记忆缺陷。在这项研究中，我们的目的是探讨褪黑激素或雌二醇在卵巢切除大鼠脑中的抗氧化作用。OVX Sprague-Dawley大鼠每天注射褪黑激素（5、10或20 mg/kg）、17 β-雌二醇（80 μ g/kg）或芝麻油，持续16周。我们发现，脑线粒体硫代巴比妥酸反应物质（TBARS）水平的增加，减少线粒体谷胱甘肽（GSH）含量以及线粒体超氧化物歧化酶（SOD）活性和上调的凋亡相关因子，如Bax，Caspase-3，前列腺凋亡反应-4（Par-4）在OVX大鼠额叶皮质。除氧化应激外，OVX还引起线粒体呼吸复合物I和复合物IV活性降低，这暗示线粒体功能障碍。褪黑素或17 β-雌二醇拮抗OVX诱导的有害作用。此外，免疫组化结果显示，凋亡相关因子如Bax，Caspase-3和（Par-4）的异常上调大大降低褪黑素或17 β-雌二醇补充作用后的表达。这些发现证明了褪黑激素或17 β-雌二醇对绝经后神经病变的重要作用，并支持褪黑激素在治疗绝经后妇女痴呆症中的潜在应用。早期、长期应用褪黑激素是一种很有前途的策略，可能会在临床环境中应用。(C)2005年爱思唯尔公司All rights reserved.
Melatonin is an endogenously generated potent antioxidant. Our previous results indicated that melatonin improved learning and memory deficits in the transgenic mouse model of Alzheimer's disease (AD) and ovariectomized (OVX) rats by improving cholinergic nerve system dysfunction, preventing apoptosis. In this study we aim to investigate the antioxidative effects of melatonin or estradiol in the brains of ovariectomized rats. OVX Sprague-Dawley rats received daily injections of melatonin (5, 10, or 20 mg/kg), 17 beta-estradiol (80 mu g/kg), or sesame oil for 16 weeks. We found an increase in brain mitochondrial thiobarbituric acid-reactive substances (TBARS) levels, a decrease in mitochondrial glutathione (GSH) content as well as mitochondrial superoxide dismutase (SOD) activity and upregulation of the apoptotic-related factors, such as Bax, Caspase-3, and Prostate apoptosis response-4 (Par-4) in the frontal cortex of OVX rats. In addition to oxidative stress, OVX also caused decreased activities of mitochondrial respiration complex I and complex IV, which implicated mitochondrial dysfunction. Melatonin or 17 beta-estradiol antagonized the detrimental effects induced by OVX. Furthermore, immunohistochemistry results revealed that the abnormal upregulation of the apoptotic related factor such as Bax, Caspase-3, and (Par-4) greatly reduced expression after melatonin or 17 beta-estradiol supplement action. These findings demonstrate the important effects of melatonin or 17 beta-estradiol on postmenopausal neuropathy and support the potential application of melatonin in the treatment of dementia in postmenopausal women. Early, long-term melatonin application is a promising strategy which could potentially be applied in a clinical setting. (C) 2005 Elsevier Inc. All rights reserved.