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褪黑素和硒联合治疗可减轻多西紫杉醇诱导的小鼠肾和睾丸细胞凋亡及氧化损伤。

Treatment with melatonin and selenium attenuates docetaxel-induced apoptosis and oxidative injury in kidney and testes of mice.

机构信息

Department of Urology, School of Medicine, Suleyman Demirel University, Isparta, Turkey.

Neuroscience Research Center, Suleyman Demirel University, Isparta, Turkey.

出版信息

Andrologia. 2019 Sep;51(8):e13320. doi: 10.1111/and.13320. Epub 2019 May 27.

Abstract

Docetaxel (DTX) has been used in cancer treatments for several decades, but it results in many adverse apoptotic effects through excessive production of reactive oxygen species (ROS) in some tissue including the kidney and testes. We aimed to investigate potential modulatory roles of melatonin (MEL) and selenium (Se) against DTX-induced apoptosis and oxidative injury in the testes and kidney of mice. Thirty-two mice were divided into four equal groups as control, DTX, DTX + MEL and DTX + Se. DTX group was treated with a single intraperitoneal dose of DTX. After DTX treatment, MEL and Se were administered to the mice in the DTX + MEL and DTX + Se groups for 7 days respectively. Increased lipid peroxidation, ROS, apoptosis, caspase-3 and caspase-9 activities in the kidney and testes of the DTX group were diminished by treatment with MEL and Se. DTX-induced decreases in vitamin E (α- and γ-tocopherol), glutathione peroxidase and reduced glutathione levels in the kidney and testis were increased following MEL and Se treatments. In conclusion, our data show that MEL and Se can act as modulators against DTX-induced apoptosis and oxidative damage in the kidney and testis through up-regulation of glutathione and vitamin E and down-regulation of caspase pathways.

摘要

多西紫杉醇(DTX)已在癌症治疗中使用了几十年,但它会在某些组织(包括肾脏和睾丸)中产生过多的活性氧物种(ROS),从而导致许多不良的凋亡作用。我们旨在研究褪黑素(MEL)和硒(Se)对 DTX 诱导的小鼠睾丸和肾脏细胞凋亡和氧化损伤的潜在调节作用。32 只小鼠被分为四组,每组 8 只,分别为对照组、DTX 组、DTX+MEL 组和 DTX+Se 组。DTX 组给予单次腹腔注射 DTX。DTX 处理后,DTX+MEL 和 DTX+Se 组的小鼠分别给予 MEL 和 Se 治疗 7 天。MEL 和 Se 处理可降低 DTX 组肾脏和睾丸中的脂质过氧化、ROS、凋亡、caspase-3 和 caspase-9 活性。DTX 诱导的肾脏和睾丸中维生素 E(α-和γ-生育酚)、谷胱甘肽过氧化物酶和还原型谷胱甘肽水平降低,经 MEL 和 Se 处理后增加。总之,我们的数据表明,MEL 和 Se 可通过上调谷胱甘肽和维生素 E 以及下调半胱天冬酶途径来作为 DTX 诱导的肾脏和睾丸细胞凋亡和氧化损伤的调节剂。

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