17β-雌二醇代谢产物在铬诱导的氧化应激中的作用。

The role of 17β-estradiol metabolites in chromium-induced oxidative stress.

作者信息

Sawicka Ewa, Długosz Anna

机构信息

Department of Toxicology, Wroclaw Medical University, Poland.

出版信息

Adv Clin Exp Med. 2017 Mar-Apr;26(2):215-221. doi: 10.17219/acem/62217.

DOI:10.17219/acem/62217

PMID:28791837

Abstract

BACKGROUND

The increasing incidence of estrogen-dependent breast cancer and the presence in the environment of a large number of factors that interact with estrogen receptors have sparked interest in chemical influences on estrogen-dependent processes. In a previous work, the authors examined the interaction of estradiol with chromium. In the present article the importance of estradiol biotransformation in these interactions is investigated. There is no information in the available literature about the role of metabolites in exposure to chromium. It seems important because estradiol metabolites have various carcinogenic abilities and their formation during biotransformation could be increased or decreased by environmental enzyme inducers or inhibitors. The metabolites could play a detoxifying role or create a toxic synergism in free radical processes induced by chromium VI (CrVI).

OBJECTIVES

The aim of this study was to evaluate the influence of 2 17β-estradiol metabolites - 4-hydroxyestradiol (4-OHE2) and 16α-hydroxyestrone (16α-OHE1) - in conditions of oxidative stress caused by CrVI.

MATERIAL AND METHODS

Human blood, erythrocytes or mitochondria isolated from human placentas after natural deliveries were used in the experiments. The influence of CrVI, 4-OHE2 and 16-OHE1 on thiobarbituric acid reactive substances (TBARS), the hydroxyl radical (•OH), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-S-transferase (GST), and the interactions of the metabolites exposed to chromium expressed by these factors were examined.

RESULTS

4-OHE2 reduced the level of TBARS induced by CrVI in mitochondria (p < 0.05) and in erythrocytes (p < 0.05), and increased SOD activity (p < 0.05). 16α-OHE1 increased the activity of GST in erythrocytes exposed to CrVI (p < 0.05).

CONCLUSIONS

The metabolites do not have toxic interactions with CrVI. On the contrary, they exhibited a protective effect. The mechanism of protection varied: 4-OHE2 decreased TBARS and increased SOD activity, while 16α-OHE1 increased GST activity.

摘要

背景

雌激素依赖性乳腺癌的发病率不断上升，且环境中存在大量与雌激素受体相互作用的因素，这引发了人们对化学物质对雌激素依赖性过程影响的关注。在之前的一项研究中，作者研究了雌二醇与铬的相互作用。在本文中，研究了雌二醇生物转化在这些相互作用中的重要性。现有文献中没有关于代谢产物在铬暴露中作用的信息。这似乎很重要，因为雌二醇代谢产物具有多种致癌能力，并且它们在生物转化过程中的形成可能会因环境酶诱导剂或抑制剂而增加或减少。这些代谢产物可能在六价铬（CrVI）诱导的自由基过程中发挥解毒作用或产生毒性协同作用。

目的

本研究的目的是评估两种17β-雌二醇代谢产物——4-羟基雌二醇（4-OHE2）和16α-羟基雌酮（16α-OHE1）——在CrVI引起的氧化应激条件下的影响。

材料与方法

实验使用自然分娩后从人胎盘分离的人血、红细胞或线粒体。研究了CrVI、4-OHE2和16-OHE1对硫代巴比妥酸反应性物质（TBARS）、羟基自由基（•OH）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）和谷胱甘肽-S-转移酶（GST）的影响，以及这些因素所表达的暴露于铬的代谢产物之间的相互作用。