Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040, Madrid, Spain.
Neurotox Res. 2011 Oct;20(3):240-9. doi: 10.1007/s12640-010-9237-4. Epub 2011 Jan 11.
This study was undertaken to examine whether cadmium oral exposure modifies biogenic amine concentration at hypothalamic level in adult male rats, and to investigate the possible modulatory effects of melatonin against cadmium-induced changes on these neurotransmitters. For this purpose, rats were exposed to cadmium (25 mg/l of CdCl(2) in the drinking water) with or without melatonin (30 μg/rat/day intraperitoneally) for 30 days. Norepinephrine (NE), dopamine (DA), serotonin (5-HT), 3,4-dihydroxyphenyl acetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) were quantified by high performance liquid chromatography (HPLC). Oral cadmium administration led to decrease of NE, DA, and 5-HT content and DA turnover within the three hypothalamic regions examined, and therefore an inhibition of 5-HT turnover at posterior hypothalamus. Sensitivity to melatonin was specific to the hypothalamic region evaluated. Thus, the anterior hypothalamus was not nearly sensitive to exogenously administered melatonin, whereas the neurohormone decreased the content of these amines in the mediobasal hypothalamus, and melatonin increased it in the posterior hypothalamic region. Melatonin effectively prevented some cadmium-induced alterations on hypothalamic amine concentration. This is the case of DA in the anterior and posterior hypothalamus, and 5-HT metabolism in the posterior hypothalamic region. In conclusion, the obtained results indicate that melatonin treatment may be effective modulating some neurotoxic effects induced by cadmium exposure, and, more to the point, a possible role of this indolamine as a preventive agent for environmental or occupational cadmium contamination.
本研究旨在探讨镉经口暴露是否会改变成年雄性大鼠下丘脑水平的生物胺浓度,并研究褪黑素对镉引起这些神经递质变化的可能调节作用。为此,将大鼠暴露于镉(饮用水中 25mg/l 的 CdCl2),同时或不给予褪黑素(30μg/大鼠/天腹腔内)30 天。通过高效液相色谱法(HPLC)定量测定去甲肾上腺素(NE)、多巴胺(DA)、血清素(5-HT)、3,4-二羟基苯乙酸(DOPAC)和 5-羟吲哚乙酸(5-HIAA)。口服镉给药导致三个下丘脑区域内的 NE、DA 和 5-HT 含量以及 DA 周转率降低,并因此抑制了后下丘脑的 5-HT 周转率。褪黑素的敏感性针对所评估的下丘脑区域具有特异性。因此,前下丘脑对给予的外源性褪黑素几乎不敏感,而神经激素降低了中基底下丘脑的这些胺的含量,并增加了后下丘脑区域的含量。褪黑素有效地预防了一些镉引起的下丘脑胺浓度改变。在前和后下丘脑的 DA 以及后下丘脑区域的 5-HT 代谢中就是这种情况。总之,所得结果表明,褪黑素治疗可能有效调节镉暴露引起的一些神经毒性作用,更重要的是,这种吲哚胺作为环境或职业性镉污染的预防剂可能具有作用。