Table 3.

Aluminum-induced cytotoxicity in vitro.

Compound	System	ExposureDuration	Concentration	Response/Comments	References
Al glycinate (Tokyo Kasei Kogyo)	Cultured mouse primary cortical astrocytes	48 h or 6–12 h followed by 7 day control media culture	0.1 mM	No change anti-apoptotic Bcl2, pro-apoptotic Bax, IRE1α, PERK, Bbc3/PUMA, ATF6α, ATF6β, CHOP/GADD15, OASIS, STC2 ↑ Ire1β after 6–12 h indicates endoplasmic reticulum stress No concentration-response data	Aremu et al. (2011)
Al (C3H5O3)3	Synthetic Aβ1–42 SH-SY5Y Human neoblastoma cells	48 h AβPP measures 72 h tau 181 measures	5 μM Al 0.5 μM Aβ-Al	↑Aβ-Al annular protofibrils and fibril oligomers ↑ Aβ-Al spherical oligomers and extended β-sheet ↑AβPPα at 48 and 72 h after Aβ-Al ↑tau 181 at 72 h after Aβ-Al	Bolognin et al. (2011)
AlCl3 (Sigma) Aβ(25–35)	SH-SY5Y Human neuroblastoma cells	24, 48, 72 and 96 h	1, 10, 50, 100 and 300 μM Al 2, 10, 20 and 100 μM Aβ(25–35)	↑Lethality at > 10 μM Aβ(25–35) No change mitochrondrial activity ≤ 300 μM Al Al dose-dependent ↑ death after co-treatment with 2 μM Aβ(25–35) ↓ β-secretase (BACE1 and BACE2) expression with 10 μM Al and 2 μM Aβ(25–35)	Castorina et al. (2010)
Al maltolate	SH-SY5Y Human neuroblastoma cells	24 h	50–800 μM	No change viability or morphology at ≤ 200 μM ↓Cell bodies, neuritis and viability at ≥ 400 μM ↓ Brain-derived neurotrophic factor (BNDF)-induced cytoskeleton-associated protein (Arc) expression at ≥ 200 μM ↓ BDNF-enhanced phosphor-ERK expression at 200 μM ↓ BDNF-induced phosphorylation, 4EBP, p70S6K, elF4E at 200 μM	Chen et al. (2011a)
Al maltolate	Sprague-Dawley rat cortical neurons	1, 3, 5, and 7 days	5–200 μM or 12.5 μM for 7 days	↓Viability at 7 days with 12.5 μM No change sAPPα or full-length cellular AβPP Co-treatment with 25 μM Rho-kinase inhibitor Y-27632 ↓ cytotoxicity and amyloid fibrils	Chen et al. (2010a)
AlCl3 • 6H2O (Sigma)	Synthetic Aβ40 peptide	2–100 s	500 μM – 20 mM	↓Aβ oligomerization with Al at ≥ 50 μM Zn+2 and Cu+2 ↑Aβ oligomer formation ↑Buffer acidity and ↑Aβ amorphous aggregation at > 200 μM ↑ Aβ hydrophobic cluster exposure at 500 μM	Chen et al. (2011b)
Al+3 (Perkin Elmer stock solution; chemical form not stated)	Synthetic human pro IAPP (1–48) (pancreatic islet amyloid polypeptide)	7–14 days	320 μM	↓ProIAPP (1–48) amyloid formation ↑ProIAPP (1–48) spherulites	Exley et al. (2010)
KAl(SO4)3	10 nM Recombinant insulin-degrading enzyme Synthetic Aβ1–16 Synthetic Aβ16–28	0.5–5.0 h	100 μM	No influence of Al+3 on IDE activity	Grasso et al. (2011)
AlCl3 (source and chemical purity not specified)	Cell-free clarified rhodamine-conjugated 5 μm phosphorylated neurofilaments (NF) from adult C57/BalbC mouse spinal cord	30 min	1 μM – 4 mM	Dose-dependent ↑ neurofilament aggregation NF dephosphorylation by cakineurin inhibited AlCl3 – induced aggregation	Kushkuley et al. (2010)
Al lactate (source and chemical purity not specified)	Human CCF-STTG1 astrocytes Human HepG2 hepatocytes	24 h	0, 0.01–0.1 mM 0, 0.01–0.25 mM	Dose-dependent ↑ α-ketoglutarate and lipid accumulation ↓ γ-Butyrobetaine aldehyde dehydrogenase ↓ Butyrobetaine dioxygenase	Lemire et al. (2011)
K[Al (C7H11O6)3] (Al quinate)	Primary Sprague-Dawley rat hippocampal cells	3 or 24 h 96 h	10, 100 or 500 μM Al+ 3	Dose-dependent ↓ neuron survival at 3 h ↓ Glial cell survival at 500 μM at 3 h	Nday et al. (2010)
Soluble Al+ 3 (1% HCl, Sigma) with 50 μM Na citrate (Sigma)	Mouse N2a neuroblastoma cells expressing APP695 isoform 8.2 pg Aβ(1–40)/ml negligible Aβ(1–42)			Aβ(1–40) ↑ neuronal and glial cell death No change cell survival after Aβ (1–40) and 50 μM Al + 3 K[Al (C7H11O6)3] toxicity reduced compared to Al +3
Al2 (SO4)3	Saccharomyces cerevisiae BY4743	24 h	0–3.2 mM	↓ Concentration-dependent growth at 0.8–1.6 mM Disruption of Pdr5p detoxication pathway ↑Al + 3 accumulation and ↑ cytotoxicity	Wu et al. (2012c)
AlCl3 Tridecameric Al polycationic sulfate (nano-Al13)	Porcine heart malate dehydrogenase	0–400 s	0 or 30 mM	↑ Malate dehydrogenase at pH 7.5	Yang et al. (2011)
Al maltolate AlCl3	Sprague-Dawley rat (3 day old neonate) primary cortical astrocytes	12, 24, 48 and 72 h	0, 200, 400, 800, 1600 μM	Concentration and duration-dependent ↑ apoptosis and lethality ↑ Beclin 1 ↑ LC3II ↓ LC3I Al maltolate was more potent than AlCl3	Zeng et al. (2011)
AlCl3 • H2O	Human neuroblastoma SH-SY5Y	48 h	0 or 2–8 mM	Concentration ↑ apoptosis and necrosis Percentage of cells with necorsis was always higher than those with apoptosis Treatment with caspase-3 siRNA and Nec-1 reduced cell death	Zhang et al. (2010a)
AlCl3 • H2O	Rat gliatoma C6	24 h	0 or 1–8 mM	↑ apoptosis ↑ necrosis ↑cytochrome c release ↑ Bax expression	Zhang et al. (2010b)