Doctorado en Ciencias Biológicas y de la Salud, Div. de CBS, Universidad Autónoma Metropolitana, Calzada del Hueso 1100 Colonia Villa Quietud, C.P.04960, Mexico City, Mexico.
Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Insurgentes Sur 3877, La Fama, Tlalpan, CP14269, Mexico City, Mexico.
Biometals. 2021 Jun;34(3):687-700. doi: 10.1007/s10534-021-00304-1. Epub 2021 Apr 26.
Neurodegenerative disorders have been linked to the decrease of copper concentrations in different regions of the brain. Therefore, intake of micronutrient supplements could be a therapeutic alternative. Since the copper distribution profile has not been elucidated yet, the aim of this study was to characterize and to analyze the concentration profile of a single administration of copper gluconate to rats by two routes of administration. Male Wistar rats were divided into three groups. The control group received vehicle (n = 5), and the experimental groups received 79.5 mg/kg of copper orally (n = 4-6) or 0.64 mg/kg of copper intravenously. (n = 3-4). Blood, striatum, midbrain and liver samples were collected at different times. Copper concentrations were assessed using atomic absorption spectrophotometry. Copper concentration in samples from the control group were considered as baseline. The highest copper concentration in plasma was observed at 1.5 h after oral administration, while copper was quickly compartmentalized within the first hour after intravenous administration. The striatum evidenced a maximum metal concentration at 0.25 h for both routes of administration, however, the midbrain did not show any change. The highest concentration of the metal was held by the liver. The use of copper salts as replacement therapy should consider its rapid and discrete accumulation into the brain and the rapid and massive distribution of the metal into the liver for both oral and intravenous routes. Development of controlled-release pharmaceutical formulations may overcome the problems that the liver accumulation may imply, particularly, for hepatic copper toxicity.
神经退行性疾病与大脑不同区域铜浓度的降低有关。因此,摄入微量营养素补充剂可能是一种治疗选择。由于铜的分布情况尚未阐明,本研究的目的是通过两种给药途径来描述和分析单次给予葡萄糖酸铜后铜在大鼠体内的浓度分布。雄性 Wistar 大鼠分为三组。对照组给予载体(n = 5),实验组给予 79.5 mg/kg 铜口服(n = 4-6)或 0.64 mg/kg 铜静脉内给药(n = 3-4)。在不同时间采集血液、纹状体、中脑和肝脏样本。使用原子吸收分光光度法测定铜浓度。对照组样本中的铜浓度被认为是基线。口服给药后 1.5 小时观察到血浆中铜浓度最高,而静脉内给药后 1 小时内铜迅速分隔。两种给药途径的纹状体均在 0.25 小时达到最大金属浓度,而中脑没有任何变化。金属浓度最高的是肝脏。作为替代治疗使用铜盐应考虑到其在脑内的快速和离散积累以及金属在肝内的快速和大量分布,无论是口服还是静脉内途径。开发控释药物制剂可能会克服肝脏积累可能带来的问题,特别是对肝铜毒性。