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依布硒啉能否预防顺铂诱导的卵巢损伤?

Can ebselen prevent cisplatin-induced ovarian damage?

作者信息

Soyman Zeynep, Uzun Hafize, Bayindir Nihan, Esrefoglu Mukaddes, Boran Birtan

机构信息

Department of Obstetrics and Gynecology, Ministry of Health, Istanbul Education and Research Hospital, Istanbul, Turkey.

Department of Biochemistry, Istanbul University Cerrahpasa School of Medicine, Istanbul, Turkey.

出版信息

Arch Gynecol Obstet. 2018 Jun;297(6):1549-1555. doi: 10.1007/s00404-018-4750-4. Epub 2018 Mar 29.

Abstract

PURPOSE

The occurrence of ovarian damage is a major shortcoming in treating tumors with cisplatin (CP). The present study investigates the beneficial effects of ebselen-a seleno-organic compound with antioxidant and antiinflammatory properties-vis-à-vis CP-induced ovarian damage.

METHODS

Twenty-eight adult female rats were divided into four study groups. Group 1 received no treatment. The rats in Groups 2, 3, and 4 were intraperitoneally administered CP (2 mg/kg/day) twice per week, for 5 weeks. Those in Group 2 received 0.3 ml saline (0.9% NaCl) intraperitoneally 60 min before each CP treatment, while those in Group 3 received 0.2 ml dimethyl sulfoxide (DMSO) and 0.3 ml saline intraperitoneally 60 min before each CP treatment. The rats in Group 4 were pretreated with an intraperitoneal injection of 15 mg/kg/day ebselen 60 min before each CP treatment. Ovarian tissue malondialdehyde (MDA), total nitric oxide (NOx), glutathione (GSH), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), and catalase levels, as well as histopathological damage scores (HDSs) and serum antimullerian hormone (AMH) levels, were assessed.

RESULTS

Cu/Zn-SOD and GSH levels were significantly higher, and MDA and NOx levels significantly lower, in Group 4 than in Groups 2 and 3. Pretreatment with ebselen significantly improved serum AMH levels, relative to Groups 2 and 3. Additionally, HDS values were significantly lower in Group 4 than in Groups 2 and 3.

CONCLUSIONS

Our results from using an experimental rat model of CP chemotherapy suggest that ebselen use may ameliorate ovarian damage by preventing oxidative injury.

摘要

目的

顺铂(CP)治疗肿瘤时卵巢损伤的发生是一个主要缺点。本研究调查了依布硒啉(一种具有抗氧化和抗炎特性的有机硒化合物)对CP诱导的卵巢损伤的有益作用。

方法

将28只成年雌性大鼠分为四个研究组。第1组不接受治疗。第2、3和4组大鼠每周两次腹腔注射CP(2毫克/千克/天),共5周。第2组在每次CP治疗前60分钟腹腔注射0.3毫升生理盐水(0.9%氯化钠),而第3组在每次CP治疗前60分钟腹腔注射0.2毫升二甲基亚砜(DMSO)和0.3毫升生理盐水。第4组在每次CP治疗前60分钟腹腔注射15毫克/千克/天的依布硒啉进行预处理。评估卵巢组织丙二醛(MDA)、总一氧化氮(NOx)、谷胱甘肽(GSH)、铜/锌超氧化物歧化酶(Cu/Zn-SOD)和过氧化氢酶水平,以及组织病理学损伤评分(HDSs)和血清抗苗勒管激素(AMH)水平。

结果

第4组的Cu/Zn-SOD和GSH水平显著高于第2组和第3组,MDA和NOx水平显著低于第2组和第3组。与第2组和第3组相比,依布硒啉预处理显著提高了血清AMH水平。此外,第4组的HDS值显著低于第2组和第3组。

结论

我们使用CP化疗实验大鼠模型的结果表明,使用依布硒啉可能通过预防氧化损伤来减轻卵巢损伤。

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