Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, India.
Climacteric. 2013 Aug;16(4):426-37. doi: 10.3109/13697137.2012.696292. Epub 2012 Sep 27.
Estrogen deprivation after menopause is associated with increased oxidative stress. The present study was designed to study the role of sesamol (3,4-methylenedioxyphenol), a phenolic antioxidant and anti-inflammatory molecule, in oxidative stress-induced changes in three major affected organ systems, the central nervous system, the cardiovascular system and the skeletal system in ovariectomized rats, a widely used animal model of menopause.
Animals were divided into eight different groups (n = 6-8). Five groups underwent ovariectomy; starting from the 2nd day of ovariectomy, three of these groups received sesamol (2, 4, 8 mg/kg) and the fourth group was administered α-tocopherol (100 mg/kg) orally for 7 weeks. The fifth ovariectomized group did not receive any drug treatment. Rats in the naïve (non-operated) and sham-operated groups did not receive any drug treatment, while the eighth group consisted of naïve animals which were treated for 7 weeks with only sesamol 8 mg/kg orally daily. After 7 weeks, animals were subjected to testing of behavioral paradigms (elevated plus maze and Morris water maze for assessment of anxiety and memory, respectively) 24 h after the last dose. After behavioral studies, animals were sacrificed for various biochemical estimations.
Administration of sesamol (2, 4, 8 mg/kg orally) to ovariectomized rats for 7 weeks significantly and dose-dependently improved memory, attenuated anxiety, decreased oxidative stress in brain, improved the serum lipid profile and reduced serum tumor necrosis factor-α levels when compared with ovariectomized control rats. Similar protective effects were observed in the case of the skeletal system studies. Sesamol increased the bone ash content and the mechanical stress parameters in treated groups.
The results emphasize the involvement of oxidative stress and inflammation in the development of ovariectomy-induced pathophysiological changes and point towards the therapeutic potential of sesamol in menopausal pathologies.
绝经后雌激素的缺乏与氧化应激的增加有关。本研究旨在研究芝麻酚（3,4-亚甲二氧基苯酚），一种酚类抗氧化剂和抗炎分子，在卵巢切除大鼠的三个主要受影响的器官系统（中枢神经系统、心血管系统和骨骼系统）中氧化应激诱导的变化中的作用，卵巢切除术是一种广泛使用的绝经动物模型。
动物分为八组（n = 6-8）。五组进行卵巢切除术；从卵巢切除后的第 2 天开始，其中三组接受芝麻酚（2、4、8mg/kg）口服治疗，第四组给予α-生育酚（100mg/kg）口服治疗，共 7 周。第五组卵巢切除大鼠未接受任何药物治疗。未接受任何药物治疗的天真（未手术）和假手术组大鼠，而第八组由仅接受 7 周芝麻酚 8mg/kg 口服治疗的天真动物组成。7 周后，动物在最后一次给药后 24 小时进行行为范式测试（高架十字迷宫和 Morris 水迷宫分别用于评估焦虑和记忆）。行为研究后，动物被处死进行各种生化测定。
7 周口服芝麻酚（2、4、8mg/kg）治疗卵巢切除大鼠可显著改善记忆，减轻焦虑，减少大脑氧化应激，改善血清脂质谱，降低血清肿瘤坏死因子-α水平，与卵巢切除对照组大鼠相比。在骨骼系统研究中也观察到类似的保护作用。芝麻酚增加了治疗组的骨灰分含量和力学应激参数。
这些结果强调了氧化应激和炎症在卵巢切除引起的病理生理变化发展中的作用，并指出芝麻酚在绝经相关疾病中的治疗潜力。
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