Deferoxamine ameliorated Al(mal)₃-induced neuronal ferroptosis in adult rats by chelating brain iron to attenuate oxidative damage

Abstract

Aluminum (Al), a neurotoxic element, can induce Alzheimer’s disease-like (AD-like) changes by triggering neuronal death. Iron homeostasis disturbance has also been implicated in Alzheimer’s disease (AD), and excess iron exacerbates oxidative damage and cognitive defects. Ferroptosis is a nonapoptotic form of cell death dependent upon intracellular iron. However, the involvement of neuronal death induced by aluminum maltolate (Al(mal)₃) in the pathogenesis of AD remains elusive. In this study, the results of three different behavioral experiments suggested that the learning and memory ability deteriorated and autonomous activity declined of these rats that exposed Al(mal)₃ were alleviated by deferoxamine (DFO). Transmission electron microscope observations showed that the membrane was ruptured, and the membrane density increased and ridge disappearance (the most prominent characteristic of ferroptosis) in the perinuclear and cytoplasmic compartments of the hippocampal neurons were perceived in the exposure group, while the DFO group and 18 μM/kg Al(mal)₃+DFO group were alleviated compared with 18 μM/kg Al(mal)₃. In addition, DFO prevented oxidative stress, such as increased glutathione (GSH) and decreased malondialdehyde (MDA) and reactive oxygen species (ROS), while the latter two indexes had the same changing tendency as the total iron of brain tissue. These data indicated that Al(mal)₃ could cause ferroptosis in Sprague-Dawley (SD) rat neurons, which was inhibited by DFO via reducing the content of iron and increasing the ability of cells to resist oxidative damage.

Keywords:

• Aluminum
• deferoxamine
• ferroptosis
• SD rat
• oxidative damage

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

We thank the National Natural Science Foundation of China under Grant [grant numbers 81673277, 81373106]; the Provincial Natural Science Foundation of Shanxi under Grant [grant number 2013011052-1]; the Provincial Application Basis Research Plan of Shanxi under Grant [grant number 201801D121314]; Graduate Education Innovation Project in Shanxi Province under Grant [number 2021Y414]and the Shanxi Medical University Ph.D. Startup Fund Project under Grant [grant number B03201209] for financial support.