Topçuoglu A, Uzun H, Balci H, Karakus M, Coban I, Altug T, Aydin S, Topçuoglu D, Cakatay U
Department of Obstetrics and Gynecology, Izzet Baysal University, Faculty of Medicine, Bolu, Turkey.
Clin Invest Med. 2009 Apr 1;32(2):E133-43. doi: 10.25011/cim.v32i2.6031.
To assess estrogen-related changes in the redox status of the brain and liver proteins as well as the systemic oxidative stress in ovarectomised (OVX) rats
Twelve-week-old, sexually mature female Sprague-Dawley rats (200-250g) were randomly divided into four groups: The following treatment combinations were administrated daily to all in 0.05 ml 96% ethanol solution by gastric gavage. (1) Sham operation (2) OVX rats (3) OVX rats [0.02 mg/kg/day of 17beta-estradiol (E2) and 0.01 mg/kg/day of norethisterone acetate] (4) OVX rats [E2 (0.01 mg/kg/day) and drospirenon (0.02 mg/kg/day)]. Estrogen levels were determined using routine clinical-chemistry methods. We also measured protein oxidation parameters such as protein carbonyl (PCO), total thiol (T-SH) and the other oxidative stress markers malondialdehyde (MDA) and glutathione (GSH).
Ovariectomy resulted in abnormal elevation of plasma and tissue oxidative stress markers and changes in redox status of the proteins in tissue dependent manner. Supplementation of various estrogens combinations partially alleviated these abnormalities and restored redox homeostasis of proteins after the ovariectomy. Among the studied protein oxidation parameters, plasma and tissue PCO levels of the OVX rats were higher than those of the control groups (P < 0.01). Hormone replacement therapies (HRT) caused a decrease in PCO and MDA in both plasma and tissue of the OVX rats (P < 0.01). HRT in OVX rats decreased plasma MDA and increased liver and brain GSH (P < 0.01). Liver MDA levels of the Drospirenon-treated rats were lower than in the norethisterone acetate group (P < 0.01). On the other hand, Drospirenon increases brain GSH s more effectively than norethisterone acetate (P < 0.01). After bilateral oopherectomy, plasma and tissue T-SH levels decreased in the OVX group compared with control (P < 0.01). Norethisterone acetate increased plasma T-SH more effectively than Drospirenon (P < 0.05)
The study showed the extent of oxidative protein damage (OPD) in this model of estrogen deficiency. The protective effect of estrogens against tissue specific OPD suggests that estrogens play an important role within the antioxidant defense systems in plasma, liver and brain. The exact molecular mechanisms leading to these findings are not yet completely known. Meanwhile, hormone replacement therapy for the prevention of OPD in a tissue specific manner may be required.
评估去卵巢（OVX）大鼠大脑和肝脏蛋白质氧化还原状态的雌激素相关变化以及全身氧化应激情况
将12周龄、性成熟的雌性Sprague-Dawley大鼠（200 - 250g）随机分为四组：通过胃管向所有大鼠每日灌胃0.05 ml 96%乙醇溶液，给予以下治疗组合。（1）假手术组（2）去卵巢大鼠组（3）去卵巢大鼠组[17β-雌二醇（E2）0.02 mg/kg/天和醋酸炔诺酮0.01 mg/kg/天]（4）去卵巢大鼠组[E2（0.01 mg/kg/天）和屈螺酮（0.02 mg/kg/天）]。使用常规临床化学方法测定雌激素水平。我们还测量了蛋白质氧化参数，如蛋白质羰基（PCO）、总巯基（T-SH）以及其他氧化应激标志物丙二醛（MDA）和谷胱甘肽（GSH）。
去卵巢导致血浆和组织氧化应激标志物异常升高，并以组织依赖性方式改变组织中蛋白质的氧化还原状态。补充各种雌激素组合部分缓解了这些异常，并在去卵巢后恢复了蛋白质的氧化还原稳态。在所研究的蛋白质氧化参数中，去卵巢大鼠的血浆和组织PCO水平高于对照组（P < 0.01）。激素替代疗法（HRT）使去卵巢大鼠血浆和组织中的PCO和MDA降低（P < 0.01）。去卵巢大鼠的HRT降低了血浆MDA水平，并增加了肝脏和大脑中的GSH（P < 0.01）。屈螺酮治疗组大鼠的肝脏MDA水平低于醋酸炔诺酮组（P < 0.01）。另一方面，屈螺酮比醋酸炔诺酮更有效地增加大脑GSH（P < 0.01）。双侧卵巢切除术后与对照组相比，去卵巢组血浆和组织T-SH水平降低（P < 0.01）。醋酸炔诺酮比屈螺酮更有效地增加血浆T-SH（P < 0.05）
该研究显示了雌激素缺乏模型中氧化蛋白质损伤（OPD）的程度。雌激素对组织特异性OPD的保护作用表明雌激素在血浆、肝脏和大脑的抗氧化防御系统中发挥重要作用。导致这些结果的确切分子机制尚未完全明确。同时，可能需要以组织特异性方式进行激素替代疗法以预防OPD。
