Copper biodistribution after acute systemic administration of copper gluconate to rats

• Published in: Biometals 2021-06, Vol.34 (3), p.687-700
• Main Authors: García-Martínez, Betzabeth Anali, Montes, Sergio, Tristán-López, Luis, Quintanar-Guerrero, David, Melgoza, Luz María, Baron-Flores, Verónica, Ríos, Camilo
• Format: Article
• Language: English
• Subjects: Accumulation; Administration, Oral; Animals; Atomic absorption analysis; Atomic absorption spectrophotometry; Biochemistry; Biomedical and Life Sciences; Brain; Cell Biology; Controlled release; Copper; Dose-Response Relationship, Drug; Gluconates - administration & dosage; Gluconates - blood; Gluconates - pharmacokinetics; Injections, Intravenous; Intravenous administration; Life Sciences; Liver; Male; Medicine/Public Health; Mesencephalon; Metal concentrations; Microbiology; Neostriatum; Neurodegenerative diseases; Oral administration; Pharmacology/Toxicology; Plant Physiology; Rats; Rats, Wistar; Salts; Spectral analysis; Spectrophotometry; Tissue Distribution; Toxicity
• ISSN: 0966-0844; 1572-8773
• DOI: 10.1007/s10534-021-00304-1

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. Graphic abstract