Although aluminum chronic neurotoxicity is well documented, there are no well-established experimental protocols of Al exposure. In the current study, toxic effects of sub-chronic Al exposure have been evaluated in outbreed male rats (gastrointestinal administration). Forty animals were used: 10 were administered with AlCl3 water solution (2 mg/kg Al per day) for 1 month, 10 received the same concentration of AlCl3 for 3 month, and 20 (10 per observation period) saline as control. After 30 and 90 days, the animals underwent behavioral tests: open field, passive avoidance, extrapolation escape task, and grip strength. At the end of the study, the blood, liver, kidney, and brain were excised for analytical and morphological studies. The Al content was measured by inductively coupled plasma mass-spectrometry. Essential trace elements—Co, Cr, Cu, Fe, Mg, Mn, Mo, Se, and Zn—were measured in whole blood samples. Although no morphological changes were observed in the brain, liver, or kidney for both exposure terms, dose-dependent Al accumulation and behavioral differences (increased locomotor activity after 30 days) between treatment and control groups were indicated. Moreover, for 30 days exposure, strong positive correlation between Al content in the brain and blood for individual animals was established, which surprisingly disappeared by the third month. This may indicate neural barrier adaptation to the Al exposure or the saturation of Al transport into the brain. Notably, we could not see a clear neurodegeneration process after rather prolonged sub-chronic Al exposure, so probably longer exposure periods are required.
Aluminum Neurotoxicity Rats Per oral administration Sub-chronic exposure Trace elements
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The authors are grateful to Maria A. Zaitseva and co-workers for the help with animal handling and Olga N. Gaikova for providing histological images.
N.D. Solovyev acknowledges the financial support of the Russian Foundation for Basic Research (grant No. 16-33-60004 mol_a_dk).
Compliance with Ethical Standards
The study protocols were approved by Bioethics Committee of the Institute of Toxicology (protocol No. 8/16, dated 16.05.2016) and was conducted in accordance with the European Union law on the care and use of animals for scientific purposes.
Conflict of Interest
The authors declare that they have no conflict of interest.
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