Melatonin prevents the estrogenic effects of sub-chronic administration of cadmium on mice mammary glands and uterus
Melatonin prevents the estrogenic effects of sub-chronic administration of cadmium on mice mammary glands and uterus
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DOI：
10.1111/j.1600-079x.2007.00434.x
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发表时间：
2007-04-01
影响因子：
10.3
通讯作者：
Mediavilla, M. D.
中科院分区：
文献类型：
--
作者：
Alonso-Gonzalez, C.;Gonzalez, A.;Mediavilla, M. D.
镉（Cd）是一种重金属，被列为人类致癌物。职业暴露、饮食和吸烟是镉污染的主要来源。镉的致癌性取决于其氧化和雌激素作用。最近提出了镉在乳腺癌病因中的可能作用。褪黑激素，因为它的抗氧化剂和抗雌激素的性质可以抵消这种金属雌激素的毒性作用。我们的目的是确定相关剂量的镉对小鼠乳腺和子宫的影响，并测试褪黑激素是否会抵消其影响。不同年龄和雌激素状态（青春期前、成年完整、成年卵巢切除）的雌性小鼠用氯化镉（2-3 mg/kg，i. p.）处理，褪黑激素（在饮用水中10 μ g/mL）、CdCl 2+褪黑激素或稀释剂。而在青春期前的动物中，镉干扰乳腺导管的生长，并减少终端芽的数量，在成年人中，无论类固醇环境，镉发挥雌激素的作用，对乳腺，增加小叶肺泡发育和导管分支。子宫重量也增加了镉治疗的结果。褪黑素可部分抑制镉的作用。在成年卵巢切除小鼠，镉浓度与氯化镉+褪黑激素治疗的动物的血液中低于只接受镉的小鼠，相反的效果被发现在非去势动物。由于镉模仿雌激素的作用，吸烟者和在与镉有关的行业工作的妇女的乳腺癌发病率高，可以解释，因为这种金属的属性。褪黑激素的影响点，这吲哚胺作为环境或职业镉污染的预防剂的可能作用。
Cadmium (Cd) is a heavy metal classified as a human carcinogen. Occupational exposure, dietary consumption and cigarette smoking are sources of Cd contamination. Cd-induced carcinogenicity depends on its oxidative and estrogenic actions. A possible role of Cd in breast cancer etiology has been recently suggested. Melatonin, because of its antioxidant and antiestrogenic properties could counteract the toxic effects of this metalloestrogen. Our aim was both to determine the effects of relevant doses of Cd on mice mammary glands and uterus and to test whether melatonin would counteract its effects. Female mice of different ages and estrogenic status (prepuberal, adult intact, adult ovariectomized) were treated with CdCl2 (2-3 mg/kg, i.p.), melatonin (10 mu g/mL in drinking water), CdCl2 + melatonin, or diluents. Whereas in prepuberal animals Cd disturbs mammary ductal growth and reduces the number of terminal end buds, in adults, regardless of the steroidal milieu, Cd exerts estrogenic effects on mammary glands, increasing lobuloalveolar development and ductal branching. Uterine weight also increased as a result of Cd treatment. The effects of Cd are partially inhibited by melatonin. In adult ovariectomized mice, Cd concentration in blood of animals treated with CdCl2 + melatonin was lower than in mice receiving only Cd; the opposite effects were found in non-castrated animals. As Cd mimics the effect of estrogens, the high incidence of breast cancer in tobacco smokers and women working in industries related with Cd could be explained because of the properties of this metal. The effects of melatonin point to a possible role of this indoleamine as a preventive agent for environmental or occupational Cd contamination.