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吸入甲醛通过氧化应激在暴露的小鼠中诱导骨髓毒性。

Inhaled formaldehyde induces bone marrow toxicity via oxidative stress in exposed mice.

作者信息

Yu Guang-Yan, Song Xiang-Fu, Liu Ying, Sun Zhi-Wei

机构信息

School of Public Health, Jilin University, Changchun, China E-mail :

出版信息

Asian Pac J Cancer Prev. 2014;15(13):5253-7. doi: 10.7314/apjcp.2014.15.13.5253.

Abstract

Formaldehyde (FA) is an economically important chemical, and has been found to cause various types of toxic damage to the body. Formaldehyde-induced toxic damage involves reactive oxygen species (ROS) that trigger subsequent toxic effects and inflammatory responses, which may increase risk of cancer. Therefore, in the present study, we aimed to investigate the possible toxic mechanism in bone marrow caused by formaldehyde. In accordance with the principle of randomization, the mice were divided into four groups of 6 mice per group. One group was exposed to ambient air and the other three groups were exposed to different concentrations of formaldehyde (20, 40, 80 mg/m3) for 15 days in the respective inhalation chambers, 2h a day. At the end of the 15-day experimental period, all mice were killed. Bone marrow cells were obtained. Some of those were used for the determination of blood cell numbers, bone marrow karyote numbers, CFU-F, superoxide dismutase (SOD) activity and malondialdehyde (MDA) content; others were used for the determination of mitochondrial membrane potential (MMP), cell cycle and Bcl-2, Bax, CytC protein expression. WBC and PLT numbers in median and high dose groups were obvious reduced, but there was no change on RBC numbers. There was also reduced numbers of bone marrow karyotes and CFU-F in the high dose group. SOD activity was decreased, but MDA content was increased. MMP and Bcl-2 expression were decreased with increasing formaldehyde concentration, while expression of Bax and Cyt C was increased. We also observed change in cell cycling, and found that there was S phase arrest in the high dose group. Our study suggested that a certain concentration of formaldehyde could have toxic effects on the hematopoietic system, with oxidative stress as a critical effect.

摘要

甲醛(FA)是一种具有重要经济价值的化学物质,已被发现会对人体造成多种类型的毒性损害。甲醛诱导的毒性损害涉及活性氧(ROS),其会引发后续的毒性作用和炎症反应,这可能会增加患癌风险。因此,在本研究中,我们旨在探究甲醛对骨髓可能的毒性机制。按照随机化原则,将小鼠分为四组,每组6只。一组暴露于环境空气中,其他三组分别在各自的吸入舱中暴露于不同浓度的甲醛(20、40、80 mg/m³)15天,每天2小时。在15天实验期结束时,处死所有小鼠。获取骨髓细胞。其中一些用于测定血细胞数量、骨髓核细胞数量、CFU-F、超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量;其他用于测定线粒体膜电位(MMP)、细胞周期以及Bcl-2、Bax、CytC蛋白表达。中、高剂量组的白细胞和血小板数量明显减少,但红细胞数量无变化。高剂量组的骨髓核细胞数量和CFU-F也减少。SOD活性降低,但MDA含量增加。随着甲醛浓度增加,MMP和Bcl-2表达降低,而Bax和Cyt C表达增加。我们还观察到细胞周期的变化,发现高剂量组存在S期阻滞。我们的研究表明,一定浓度的甲醛可对造血系统产生毒性作用,氧化应激是关键影响因素。

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