Table 1.

Aluminum-induced neurotoxicity in laboratory animals.

Compound	Strain/Species/Sex	Exposure/Route/Frequency/Duration	Concentration/Dose	Response/Comment	References
AlCl3 (purity not specified)	Swiss mice ♂ (3–6 months of age)	Intraperitoneal Daily for 8 weeks	0 or 1.3 mg/kg-day	Duration-dependent ↑ Al in cerebellum, striatum, cortex, hypothalamus and brain stem Al measures by GFAAS	Abd El-Rahman et al. (2011)
AlCl3 (purity and source not specified)	ICR mice (23.9 ± 1.96 g)	Dietary 100 days	0, 10, 50, or 300 mg/kg-day	Dose-dependent ↑ hippocampus and cortex MDA, ↑ mitochrondrial 8-OHdG ↓ Hippocampus and cortex SOD	Rui and Yongjian (2010)
AlCl3	Kunming mice (20–25 g)	Intraperitoneal	0 or 40 mg/kg-day	No reduction body weight or abnormal clinical signs	Sun et al. (2009)
D-Galactose (chemical source and purity not specified)		Daily for 90 days	90 mg D-Galactose/kg-day	↑ Water maze escape latency at 90 days ↑ Hippocampus and cortex Aβ at 60, 75 and 90 days ↑ Hippocampus and cortex BACE1 at 45–90 days ↓ Hippocampus and cortex neprilysin (NEP) at 45–90 days
Al2(SO4)3 with 10 or 86 mg/L silicic acid	C57BL/6 mice	Drinking water 12–15 months	0.04 M (pH 3.2–3.5)	Body weight gain, food and drinking water consumption not affected; duration-dependent ↓ nitrergic neurons No concurrent Al control group	Foglio et al. (2012)
Al(NO3)3 • H2O (Aldrich)	NMRI mice (gender not specified) (30 g)	Drinking water ad libitum 3 months	450 mg/L	No concurrent vehicle control group	González-Muñoz et al. (2008a)
Al(NO3)3 • H2O (Aldrich)	NMRI mice (gender not specified) (30 g)	Drinking water ad libitum 3 months	450 mg/L	No concurrent vehicle control group	González-Muñoz et al. (2008b)
AlCl3 (purity not specified)	Sprague-Dawley rat	Daily oral gavage 8 weeks	0 or 100 mg/kg-day	Cerebral cortex, midbrain and cerebellar ↓ATP levels, ↓ATP synthesis, ↑ATP hydrolysis, ↓succinate dehydrogenase, NADPH, cytochrome oxidase, NADH dehydrogenase	Sood et al. (2011)
AlCl3 (purity not specified)	Sprague-Dawley rat	Daily oral gavage 8 weeks	0 or 100 mg/kg-day	↑Focal inflammation and NO in cerebrum and cerebellum ↑Glial cell TNF-α, NF-κB, HSP70	Sood et al. (2012)
AlCl3 (purity not specified)	Wistar rat ♀	Gastric intubation daily for 1 month then drinking water ad libitum for 5 months	500 mg/kg-day 1600 mg/L	↑ Posterior brain, liver and plasma LPO ↑ LDH release	Belaid-Nouria et al. (2012)
AlCl3 (purity not specified)	Sprague-Dawley rat ♂ ♀	Gastric intubation daily for 4 months	0 or 100 mg/kg-day	↑ Whole brain AChE, LPO, homocysteine ↓ Whole brain folate, vitamin B12, GSH ↑ Plasma glucose, cholesterol, triglycerides and NO ↑ Necrosis and neurofibrillary tangles in both ♂ and ♀	Ahmed et al. (2011)
AlCl3 (purity not specified)	Wistar rat ♂	Oral intubation daily for 3 months	0 or 50 mg/kg-day	↓ Body weight ↑ Cerebral cortex neuronal loss, hemorrhage, gliosis, Bax expression ↑ Cerebral cortex AChE, SOD, MDA, protein oxidation ↓ Cerebral cortex Na+/K+ ATPase activity, GPx, GST, GSH ↓ ChAt, NGF-TrkA and muscarinic receptor M1 expression	Bihaqi et al. (2009)
AlCl3 (source and purity not specified)	Sprague-Dawley rat ♂ (200–210 g)	Intraperitoneal injection once daily for 4 days	0 or 5.0 mg/kg-day	Rats killed 2 weeks after final injection ↑ Necrosis and mitochrondrial degeneration in cerebral cortex and pyramidal neurons ↑ Perivascular edema in cerebral cortex	Colak et al. (2011)
AlCl3 (source and purity not specified; fresh solution every 4 days)	Sprague-Dawley rat (gender not stated) (180 ± 10 g)	Intraperitoneal injection once daily for 90 days	0 or 40 mg/kg-day	↓Cerebral and cerebellar AChE, GSH-Px, GSH, SOD, catalase ↑ Cerebral and cerebellar LPO ↓ Cerebral and cerebellar Ca and Zn ↑ A disintegrin metalloprotease, P53, Bcl■2, IL-4, IL-2 ↓AChE expression	Elsaid et al. (2011)
AlCl3 (source and purity no specified)	Albino rat ♂	Intraperitoneal injection daily for 28 days	0 or 4.2 mg/kg-day	↑Cerebral cortex, cerebellum, hippocampus LPO ↓Cerebral cortex, cerebellum, hippocampus GAS, SOD, GPx, GST, Na+/K+ ATPase	Sumathi et al. (2011)
Al (chemical form, source and purity not specified)	Wistar rat ♂ (100–120 g)	Gastric intubation daily for 4 weeks	0 or 10 mg/kg-day	No change relative brain weight No change cerebral GSH, GSH-Px, SOD, glutathione reductase or catalase activities No change cerebral LPO	Nayak et al. (2010)
Al (chemical form, source and purity not specified)	Wistar rat ♂ (100–120 g)	Gastric intubation daily for 4 weeks	0 or 10 mg/kg-day	↓Body weight gain No change absolute or relative brain weight, cerebrum acid or alkaline phosphomonoesterase or aspartate aminotransferase activities ↑ Cerebrum alanine aminotransferase No change cerebrum amino acid homeostasis	Nayak et al. (2011)
Al(NO3)3 (chemical purity and source not specified)	Sprague-Dawley rat ♀ (160 ± 10 g)	Intraperitoneal injection daily for 60 days	0 or 27 mg/kg-day	↓ Fore- and midbrain AChE activity ↓ Hindbrain ATPase activity ↑ Forebrain LPO ↓ Forebrain SOD, catalase; no change GSH ↑ Cerebral neurofibrillary and Purkinje degeneration	Shrivastava 2012
AlCl3 (Sigma)	Wistar rat ♂ (500 ± 50 g)	Intrahippocampal injection Single dose	0 or 0.37 mg/kg	↓ Hippocampus AChE at 10 min, 3 hr, 3 and 30 days post-injection ↑ Hippocampus NO ↓ Number correct active avoidance responses at 28–30 days post-injection	Stevanović et al. (2011)
Al(NO3)3	Wistar rat ♂	Single intraperitoneal injection	0 or 32.5 mg/kg	↓ Forebrain, midbrain, hindbrain AChE ↑ Brain, liver, kidney LPO ↓ Brain, liver, kidney GSH	Bhadauria 2012
AlCl3 (purity not stated)	Rabbit (strain and sex not specified)	Drinking water ad libitum 3 months	0 or 20 mg/L (5–6.6 mg AlCl3/day per 1 kg rabbit	↑Total Al in brain ↑Atrophy in cerebral cortex, hippocampus ↑ Brain perivascular edema ↑ Brain LPO Spectrophotometric Al measures	Abd-Elghaffar et al. (2007)
AlCl3 (source and chemical purity not specified)	New Zealand White Rabbit	Intracerebral injection Single dose per Klatzo et al. (1965)	0 or 1.4% aqueous	↓ 16% brain cytochrome c oxidase Vmax at 10 days post-exposure ↓ Mitochondrial O2 consumption No clinical signs mentioned	Alleyne et al. (2011)