Mitochondrial toxicity of aluminium nanoparticles in comparison to its ionic form on isolated rat brain mitochondria

Abstract

The aim of this study was to evaluate the toxic effect of AlNPs on rat brain mitochondria and compare it with that of aluminium's ionic form. METHODS: Mitochondria were isolated from rat brain. Isolated mitochondria were treated with normal saline (Control) and different concentrations of aluminium ions (AlIs) and AlNPs (50, 100 and 200 μM). Then, the effect of AlNPs on electron transport chain complexes as well as various endpoints such as mitochondrial oxidative damage (reactive oxygen species, lipid peroxidation, glutathione, and protein carbonyl) and mitochondrial function were assessed. Also, apoptosis was evaluated by cytochrome c release, mitochondrial membrane potential and swelling. RESULTS: When compared to the control group, the exposure to AlNPs showed a marked elevation in oxidative stress markers and inhibition of complex III which was accompanied by disturbance in mitochondrial function. Also, AlNPs induced a signifi cant collapse of mitochondrial membrane potential, mitochondrial swelling, and cytochrome c release. CONCLUSIONS: The comparison of mitochondrial toxicity markers between both forms of aluminium revealed that the toxic effect of AlNPs on isolated brain mitochondria was substantially greater than that that caused by AlIs, which can probably be ascribed to its higher reactivity (Tab. 1, Fig. 8, Ref. 45).

Endoplasmic reticulum stress and mitochondrial injury are critical molecular drivers of AlCl3-induced testicular and epididymal distortion and dysfunction: protective role of taurine

“…Furthermore, AlCl 3 -associated mitochondrial damage was a prominent feature in the present study in Sertoli and Leydig cells, rounded spermatids, primary spermatocytes, spermatogonia, and spermatozoa. These findings were in agreement with those of Arab-Nozari et al (2019) and Skalny et al (2021).…”

Nanoparticle Effects on Stress Response Pathways and Nanoparticle–Protein Interactions

“…Treatment of mitochondria (isolated from male Wistar rat brain tissue) with Al NPs increased ROS production, depleted GSH, increased lipid peroxidation, induced mitochondrial swelling, and induced the release of Cyt c, indicating mitochondrial mediated apoptosis [ 259 ]. Since complexes I and III are the main sources of ROS formed as a by-product in the ETC, Arab-Nozari et al (2019) [ 259 ] used substrates and inhibitors for ETC complexes I and III to determine that Al NPs were producing most of the ROS through inhibition of complex III [ 221 ].…”

“…Cytochrome c is a heme protein in mitochondria that plays an essential role in the ETC and apoptosis [ 386 , 387 ]. Several studies have found upregulation of Cyt c in various cell lines and animal models, potentially due to apoptosis caused by NPs or by a different response [ 52 , 230 , 240 , 256 , 259 , 263 , 347 ]. A molecular dynamics (MD) simulation found that the adsorption of Cyt c to Si NPs was through hydrophobic interactions between key amino acid residues and the Si NPs resulting in structural stabilization.…”

Potential Toxic Effects of Aluminum Nanoparticles: An overview

“…AlNP-exposure induced inhibition of PTPN6 and phosphorylation of STAT3, resulting in increased expression of the apoptotic marker programmed cell death protein 4 (PDCD4) (Li et al, 2017). It was documented that, in vitro exposure of rat brain mitochondria to AlNPs at the concentrations of 100 and 200 μM caused marked collapse of mitochondrial membrane potential, mitochondrial swelling, and increased cytochrome c release (Arab-Nozari et al, 2019). Nogueira et al (2019) exposed human bronchial epithelial (BEAS-2B) and mouse neuroblastoma (N2A) cells to α-and η-AlNPs (0.02 -2.2 μg/cm 2 ) for 24, 48 and 72 hours.…”