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Quercetin Protects Against Chronic Aluminum-Induced Oxidative Stress and Ensuing Biochemical, Cholinergic, and Neurobehavioral Impairments in Rats

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Abstract

In this study, we investigated the protective effect of chronic quercetin (a natural flavanoid) administration against Al-induced cognitive impairments, oxidative damage, and cholinergic dysfunction in male Wistar rats. Al lactate (10 mg/kg b.wt./day) was administered intragastrically to rats which were pre-treated with quercetin (10 mg/kg b.wt./day, intragastrically) for 12 weeks. At the end of 6 or 12 weeks of the study, several behavioral parameters were carried out to evaluate cognitive functions. Further after 12 weeks of exposure, various biochemical tests and H&E staining were performed to assess the extent of oxidative damage and neurodegeneration, respectively. Al levels were also estimated in HC and CS regions of rat brain. Chronic administration of quercetin caused significant improvement in the muscle coordination, cognition, anxiety, locomotion, and initial exploratory patterns in Al-treated rats. Quercetin supplementation to Al-treated animals also reduced oxidative stress, decreased ROS production, increased MnSOD activity and glutathione levels with decreased lipid peroxidation and protein oxidation. It increased AChE activity and ATP levels in HC and CS regions of rat brain compared to Al-treated rats. Quercetin administration ameliorates Al-induced neurodegenerative changes in Al-treated rats as seen by H&E staining. Further with the help of atomic absorption spectrophotometer, we found that quercetin supplementation to Al-treated rats also decreases the accumulation of Al in the HC and CS regions of rat brain. Taken together the results of this study show that quercetin offers neuroprotection against Al-induced cognitive impairments, cholinergic dysfunction, and associated oxidative damage in rats.

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Abbreviations

Al:

Aluminum

ROS:

Reactive oxygen species

MnSOD:

Manganese superoxide dismutase

AChE:

Acetylcholinesterase

MWM:

Morris Water Maze

EPM:

Elevated Plus Maze

HC:

Hippocampus

CS:

Corpus striatum

H&E:

Hematoxylin and eosin

References

  • Aguirre-Hernandez E, Gonzalez-Trujano ME, Martinez AL, Moreno J, Kite G, Terrazas T, Soto-Hernandez M (2010) HPLC/MS analysis and anxiolytic-like effect of quercetin and kaempferol flavonoids from Tilia americana var. mexicana. J Ethnopharmacol 127(1):91–97

    Article  PubMed  CAS  Google Scholar 

  • Alleva E, Rankin J, Santucci D (1998) Neurobehavioral alteration in rodents following developmental exposure to aluminum. Toxicol Ind Health 14(1–2):209–221

    PubMed  CAS  Google Scholar 

  • Bavithra S, Selvakumar K, Pratheepa Kumari R, Krishnamoorthy G, Venkataraman P, Arunakaran J (2012) Polychlorinated biphenyl (PCBs)-induced oxidative stress plays a critical role on cerebellar dopaminergic receptor expression: ameliorative role of quercetin. Neurotox Res 21(2):149–159

    Article  PubMed  CAS  Google Scholar 

  • Baydar T, Papp A, Aydin A, Nagymajtenyi L, Schulz H, Isimer A, Sahin G (2003) Accumulation of aluminum in rat brain: does it lead to behavioral and electrophysiological changes? Biol Trace Elem Res 92(3):231–244

    Article  PubMed  CAS  Google Scholar 

  • Beal MF (1996) Mitochondria, free radicals, and neurodegeneration. Curr Opin Neurobiol 6(5):661–666

    Article  PubMed  CAS  Google Scholar 

  • Bharathi Shamasundar NM, Sathyanarayana Rao TS, Dhanunjaya Naidu M, Ravid R, Rao KS (2006) A new insight on Al-maltolate-treated aged rabbit as Alzheimer’s animal model. Brain Res Rev 52(2):275–292

    Article  Google Scholar 

  • Bhutada P, Mundhada Y, Bansod K, Bhutada C, Tawari S, Dixit P, Mundhada D (2010) Ameliorative effect of quercetin on memory dysfunction in streptozotocin-induced diabetic rats. Neurobiol Learn Mem 94(3):293–302

    Article  PubMed  CAS  Google Scholar 

  • Bongiovanni GA, Soria EA, Eynard AR (2007) Effects of the plant flavonoids silymarin and quercetin on arsenite-induced oxidative stress in CHO-K1 cells. Food Chem Toxicol 45(6):971–976

    Article  PubMed  CAS  Google Scholar 

  • Boots AW, Haenen GR, Bast A (2008) Health effects of quercetin: from antioxidant to nutraceutical. Eur J Pharmacol 585(2–3):325–337

    Article  PubMed  CAS  Google Scholar 

  • Brown MR, Sullivan PG, Dorenbos KA, Modafferi EA, Geddes JW, Steward O (2004) Nitrogen disruption of synaptoneurosomes: an alternative method to isolate brain mitochondria. J Neurosci Methods 137(2):299–303

    Article  PubMed  CAS  Google Scholar 

  • Cai Q, Rahn RO, Zhang R (1997) Dietary flavonoids, quercetin, luteolin and genistein, reduce oxidative DNA damage and lipid peroxidation and quench free radicals. Cancer Lett 119(1):99–107

    Article  PubMed  CAS  Google Scholar 

  • Cao G, Sofic E, Prior RL (1997) Antioxidant and prooxidant behavior of flavonoids: structure-activity relationships. Free Radic Biol Med 22(5):749–760

    Article  PubMed  CAS  Google Scholar 

  • Colomina MT, Roig JL, Sanchez DJ, Domingo JL (2002) Influence of age on aluminum-induced neurobehavioral effects and morphological changes in rat brain. Neurotoxicology 23(6):775–781

    Article  PubMed  CAS  Google Scholar 

  • Connor DJ, Harrell LE, Jope RS (1989) Reversal of an aluminum-induced behavioral deficit by administration of deferoxamine. Behav Neurosci 103(4):779–783

    Article  PubMed  CAS  Google Scholar 

  • Cucarella C, Montoliu C, Hermenegildo C, Saez R, Manzo L, Minana MD, Felipo V (1998) Chronic exposure to aluminum impairs neuronal glutamate-nitric oxide-cyclic GMP pathway. J Neurochem 70(4):1609–1614

    Article  PubMed  CAS  Google Scholar 

  • Davis JM, Murphy EA, Carmichael MD, Davis B (2009) Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance. Am J Physiol Regul Integr Comp Physiol 296(4):R1071–R1077

    Article  PubMed  CAS  Google Scholar 

  • Day AJ, Mellon F, Barron D, Sarrazin G, Morgan MR, Williamson G (2001) Human metabolism of dietary flavonoids: identification of plasma metabolites of quercetin. Free Radic Res 35(6):941–952

    Article  PubMed  CAS  Google Scholar 

  • Domingo JL (2006) Aluminum and other metals in Alzheimer’s disease: a review of potential therapy with chelating agents. J Alzheimers Dis 10(2–3):331–341

    PubMed  Google Scholar 

  • Dunham NW, Miya TS (1957) A note on a simple apparatus for detecting neurological deficit in rats and mice. J Am Pharm Assoc Am Pharm Assoc (Baltim) 46(3):208–209

    Article  CAS  Google Scholar 

  • Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95

    Article  PubMed  CAS  Google Scholar 

  • Evans HL (1995) Markers of neurotoxicity: from behavior to autoantibodies against brain proteins. Clin Chem 41(12 Pt 2):1874–1881

    PubMed  CAS  Google Scholar 

  • Flood JF, Landry DW, Jarvik ME (1981) Cholinergic receptor interactions and their effects on long-term memory processing. Brain Res 215(1–2):177–185

    Article  PubMed  CAS  Google Scholar 

  • Forbes WF, Gentleman JF, Maxwell CJ (1995) Concerning the role of aluminum in causing dementia. Exp Gerontol 30(1):23–32

    Article  PubMed  CAS  Google Scholar 

  • Glowinski J, Iversen LL (1966) Regional studies of catecholamines in the rat brain. I. The disposition of [3H]norepinephrine, [3H]dopamine and [3H]dopa in various regions of the brain. J Neurochem 13(8):655–669

    Article  PubMed  CAS  Google Scholar 

  • Goldberg DM, Hahn SE, Parkes JG (1995) Beyond alcohol: beverage consumption and cardiovascular mortality. Clin Chim Acta 237(1–2):155–187

    Article  PubMed  CAS  Google Scholar 

  • Gonda Z, Lehotzky K (1996) Effect of prenatal aluminium lactate exposure on conditioned taste aversion and passive avoidance task in the rat. J Appl Toxicol 16(6):529–532

    Article  PubMed  CAS  Google Scholar 

  • Gulya K, Rakonczay Z, Kasa P (1990) Cholinotoxic effects of aluminum in rat brain. J Neurochem 54(3):1020–1026

    Article  PubMed  CAS  Google Scholar 

  • Halliwell B (1992) Reactive oxygen species and the central nervous system. J Neurochem 59(5):1609–1623

    Article  PubMed  CAS  Google Scholar 

  • Hanasaki Y, Ogawa S, Fukui S (1994) The correlation between active oxygen scavenging and antioxidative effects of flavonoids. Free Radic Biol Med 16(6):845–850

    Article  PubMed  CAS  Google Scholar 

  • Harder JA, Baker HF, Ridley RM (1998) The role of the central cholinergic projections in cognition: implications of the effects of scopolamine on discrimination learning by monkeys. Brain Res Bull 45(3):319–326

    Article  PubMed  CAS  Google Scholar 

  • Havsteen BH (2002) The biochemistry and medical significance of the flavonoids. Pharmacol Ther 96(2–3):67–202

    Article  PubMed  CAS  Google Scholar 

  • Hu H, Yang YJ, Li XP, Chen GH (2005) Effect of aluminum chloride on motor activity and species-typical behaviors in mice. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 23(2):132–135

    PubMed  Google Scholar 

  • Ishisaka A, Ichikawa S, Sakakibara H, Piskula MK, Nakamura T, Kato Y, Ito M, Miyamoto KI, Tsuji A, Kawai Y, Terao J (2011) Accumulation of orally administered quercetin in brain tissue and its antioxidative effects in rats. Free Radic Biol Med 51(7):1329–1336

    Article  PubMed  CAS  Google Scholar 

  • Julka D, Sandhir R, Gill KD (1995) Altered cholinergic metabolism in rat CNS following aluminum exposure: implications on learning performance. J Neurochem 65(5):2157–2164

    Article  PubMed  CAS  Google Scholar 

  • Kaur A, Gill KD (2006) Possible peripheral markers for chronic aluminium toxicity in Wistar rats. Toxicol Ind Health 22(1):39–46

    Article  PubMed  CAS  Google Scholar 

  • Kaur A, Joshi K, Minz RW, Gill KD (2006) Neurofilament phosphorylation and disruption: a possible mechanism of chronic aluminium toxicity in Wistar rats. Toxicology 219(1–3):1–10

    Article  PubMed  CAS  Google Scholar 

  • Kaur R, Chopra K, Singh D (2007) Role of alpha2 receptors in quercetin-induced behavioral despair in mice. J Med Food 10(1):165–168

    Article  PubMed  CAS  Google Scholar 

  • Kawabata K, Kawai Y, Terao J (2010) Suppressive effect of quercetin on acute stress-induced hypothalamic-pituitary-adrenal axis response in Wistar rats. J Nutr Biochem 21(5):374–380

    Article  PubMed  CAS  Google Scholar 

  • Kelsey NA, Wilkins HM, Linseman DA (2010) Nutraceutical antioxidants as novel neuroprotective agents. Molecules 15(11):7792–7814

    Article  PubMed  CAS  Google Scholar 

  • Kumar A, Goyal R (2008) Quercetin protects against acute immobilization stress-induced behaviors and biochemical alterations in mice. J Med Food 11(3):469–473

    Article  PubMed  CAS  Google Scholar 

  • Kumar A, Seghal N, Naidu PS, Padi SS, Goyal R (2007) Colchicines-induced neurotoxicity as an animal model of sporadic dementia of Alzheimer’s type. Pharmacol Rep 59(3):274–283

    PubMed  CAS  Google Scholar 

  • Kumar A, Sehgal N, Kumar P, Padi SS, Naidu PS (2008a) Protective effect of quercetin against ICV colchicine-induced cognitive dysfunctions and oxidative damage in rats. Phytother Res 22(12):1563–1569

    Article  PubMed  CAS  Google Scholar 

  • Kumar V, Bal A, Gill KD (2008b) Impairment of mitochondrial energy metabolism in different regions of rat brain following chronic exposure to aluminium. Brain Res 1232:94–103

    Article  PubMed  CAS  Google Scholar 

  • Leanza G, Muir J, Nilsson OG, Wiley RG, Dunnett SB, Bjorklund A (1996) Selective immunolesioning of the basal forebrain cholinergic system disrupts short-term memory in rats. Eur J Neurosci 8(7):1535–1544

    Article  PubMed  CAS  Google Scholar 

  • Leuner K, Hauptmann S, Abdel-Kader R, Scherping I, Keil U, Strosznajder JB, Eckert A, Muller WE (2007) Mitochondrial dysfunction: the first domino in brain aging and Alzheimer’s disease? Antioxid Redox Signal 9(10):1659–1675

    Article  PubMed  CAS  Google Scholar 

  • Liang FQ, Godley BF (2003) Oxidative stress-induced mitochondrial DNA damage in human retinal pigment epithelial cells: a possible mechanism for RPE aging and age-related macular degeneration. Exp Eye Res 76(4):397–403

    Article  PubMed  CAS  Google Scholar 

  • Lien EJ, Ren S, Bui HH, Wang R (1999) Quantitative structure-activity relationship analysis of phenolic antioxidants. Free Radic Biol Med 26(3–4):285–294

    Article  PubMed  CAS  Google Scholar 

  • Liu J, Yu H, Ning X (2006) Effect of quercetin on chronic enhancement of spatial learning and memory of mice. Sci China C Life Sci 49(6):583–590

    Article  PubMed  CAS  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275

    PubMed  CAS  Google Scholar 

  • Lu J, Zheng YL, Luo L, Wu DM, Sun DX, Feng YJ (2006) Quercetin reverses d-galactose induced neurotoxicity in mouse brain. Behav Brain Res 171(2):251–260

    Article  PubMed  CAS  Google Scholar 

  • MacMillan-Crow LA, Crow JP, Kerby JD, Beckman JS, Thompson JA (1996) Nitration and inactivation of manganese superoxide dismutase in chronic rejection of human renal allografts. Proc Natl Acad Sci USA 93(21):11853–11858

    Article  PubMed  CAS  Google Scholar 

  • Mattson MP (2004) Pathways towards and away from Alzheimer’s disease. Nature 430(7000):631–639

    Article  PubMed  CAS  Google Scholar 

  • Miu AC, Andreescu CE, Vasiu R, Olteanu AI (2003) A behavioral and histological study of the effects of long-term exposure of adult rats to aluminum. Int J Neurosci 113(9):1197–1211

    Article  PubMed  Google Scholar 

  • Moridani MY, Pourahmad J, Bui H, Siraki A, O’Brien PJ (2003) Dietary flavonoid iron complexes as cytoprotective superoxide radical scavengers. Free Radic Biol Med 34(2):243–253

    Article  PubMed  CAS  Google Scholar 

  • Morris R (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11(1):47–60

    Article  PubMed  CAS  Google Scholar 

  • Muthukumaran S, Sudheer AR, Menon VP, Nalini N (2008) Protective effect of quercetin on nicotine-induced prooxidant and antioxidant imbalance and DNA damage in Wistar rats. Toxicology 243(1–2):207–215

    Article  PubMed  CAS  Google Scholar 

  • Nagata H, Takekoshi S, Takagi T, Honma T, Watanabe K (1999) Antioxidative action of flavonoids, quercetin and catechin, mediated by the activation of glutathione peroxidase. Tokai J Exp Clin Med 24(1):1–11

    PubMed  CAS  Google Scholar 

  • Navarro A, Sanchez Del Pino MJ, Gomez C, Peralta JL, Boveris A (2002) Behavioral dysfunction, brain oxidative stress, and impaired mitochondrial electron transfer in aging mice. Am J Physiol Regul Integr Comp Physiol 282(4):R985–R992

    PubMed  CAS  Google Scholar 

  • Necheles TF, Maldonado N, Barquet-Chediak A, Allen DM (1969) Homozygous erythrocyte glutathione-peroxidase deficiency: clinical and biochemical studies. Blood 33(2):164–169

    PubMed  CAS  Google Scholar 

  • Paulke A, Schubert-Zsilavecz M, Wurglics M (2006) Determination of St. John’s wort flavonoid-metabolites in rat brain through high performance liquid chromatography coupled with fluorescence detection. J Chromatogr B Analyt Technol Biomed Life Sci 832(1):109–113

    Article  PubMed  CAS  Google Scholar 

  • Piala JJ, High JP, Hassert GL Jr, Burke JC, Craver BN (1959) Pharmacological and acute toxicological comparisons of triflupromazine and chlorpromazine. J Pharmacol Exp Ther 127:55–65

    PubMed  CAS  Google Scholar 

  • Power AE, Vazdarjanova A, McGaugh JL (2003) Muscarinic cholinergic influences in memory consolidation. Neurobiol Learn Mem 80(3):178–193

    Article  PubMed  CAS  Google Scholar 

  • Pu F, Mishima K, Irie K, Motohashi K, Tanaka Y, Orito K, Egawa T, Kitamura Y, Egashira N, Iwasaki K, Fujiwara M (2007) Neuroprotective effects of quercetin and rutin on spatial memory impairment in an 8-arm radial maze task and neuronal death induced by repeated cerebral ischemia in rats. J Pharmacol Sci 104(4):329–334

    Article  PubMed  CAS  Google Scholar 

  • Richetti SK, Blank M, Capiotti KM, Piato AL, Bogo MR, Vianna MR, Bonan CD (2011) Quercetin and rutin prevent scopolamine-induced memory impairment in zebrafish. Behav Brain Res 217(1):10–15

    Article  PubMed  CAS  Google Scholar 

  • Roig JL, Fuentes S, Teresa Colomina M, Vicens P, Domingo JL (2006) Aluminum, restraint stress and aging: behavioral effects in rats after 1 and 2 years of aluminum exposure. Toxicology 218(2–3):112–124

    Article  PubMed  CAS  Google Scholar 

  • Sampson L, Rimm E, Hollman PC, de Vries JH, Katan MB (2002) Flavonol and flavone intakes in US health professionals. J Am Diet Assoc 102(10):1414–1420

    Article  PubMed  Google Scholar 

  • Santibanez M, Bolumar F, Garcia AM (2007) Occupational risk factors in Alzheimer’s disease: a review assessing the quality of published epidemiological studies. Occup Environ Med 64(11):723–732

    Article  PubMed  Google Scholar 

  • Santucci D, Rankin J, Laviola G, Aloe L, Alleva E (1994) Early exposure to aluminium affects eight-arm maze performance and hippocampal nerve growth factor levels in adult mice. Neurosci Lett 166(1):89–92

    Article  PubMed  CAS  Google Scholar 

  • Selvakumar K, Bavithra S, Suganthi M, Benson CS, Elumalai P, Arunkumar R, Krishnamoorthy G, Venkataraman P, Arunakaran J (2012) Protective role of quercetin on PCBs-induced oxidative stress and apoptosis in hippocampus of adult rats. Neurochem Res 37(4):708–721

    Article  PubMed  CAS  Google Scholar 

  • Sharma DR, Sunkaria A, Bal A, Bhutia YD, Vijayaraghavan R, Flora SJ, Gill KD (2009) Neurobehavioral impairments, generation of oxidative stress and release of pro-apoptotic factors after chronic exposure to sulphur mustard in mouse brain. Toxicol Appl Pharmacol 240(2):208–218

    Article  PubMed  CAS  Google Scholar 

  • Singh A, Naidu PS, Kulkarni SK (2003) Reversal of aging and chronic ethanol-induced cognitive dysfunction by quercetin a bioflavonoid. Free Radic Res 37(11):1245–1252

    Article  PubMed  CAS  Google Scholar 

  • Slikkker W, Youdim M, Palmer GC, Hall E, Williams C, Trembly B (1999) The future of neuroprotection. Ann N Y Acad Sci 890:529–533

    Article  PubMed  CAS  Google Scholar 

  • Solfrizzi V, Colacicco AM, D’Introno A, Capurso C, Parigi AD, Capurso SA, Torres F, Capurso A, Panza F (2006) Macronutrients, aluminium from drinking water and foods, and other metals in cognitive decline and dementia. J Alzheimers Dis 10(2–3):303–330

    PubMed  Google Scholar 

  • Suarez-Fernandez MB, Soldado AB, Sanz-Medel A, Vega JA, Novelli A, Fernandez-Sanchez MT (1999) Aluminum-induced degeneration of astrocytes occurs via apoptosis and results in neuronal death. Brain Res 835(2):125–136

    Article  PubMed  CAS  Google Scholar 

  • Tedeschi RE, Tedeschi DH, Mucha A, Cook L, Mattis PA, Fellows EJ (1959) Effects of various centrally acting drugs on fighting behavior of mice. J Pharmacol Exp Ther 125(1):28–34

    PubMed  CAS  Google Scholar 

  • Tilson HA (1993) Neurobehavioral methods used in neurotoxicological research. Toxicol Lett 68(1–2):231–240

    Article  PubMed  CAS  Google Scholar 

  • Tota S, Awasthi H, Kamat PK, Nath C, Hanif K (2010) Protective effect of quercetin against intracerebral streptozotocin induced reduction in cerebral blood flow and impairment of memory in mice. Behav Brain Res 209(1):73–79

    Article  PubMed  CAS  Google Scholar 

  • Vafeiadou K, Vauzour D, Spencer JP (2007) Neuroinflammation and its modulation by flavonoids. Endocr Metab Immune Disord Drug Targets 7(3):211–224

    Article  PubMed  CAS  Google Scholar 

  • Vannucchi MG, Scali C, Kopf SR, Pepeu G, Casamenti F (1997) Selective muscarinic antagonists differentially affect in vivo acetylcholine release and memory performances of young and aged rats. Neuroscience 79(3):837–846

    Article  PubMed  CAS  Google Scholar 

  • Walf AA, Frye CA (2007) The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc 2(2):322–328

    Article  PubMed  CAS  Google Scholar 

  • Ward CP, Redd K, Williams BM, Caler JR, Luo Y, McCoy JG (2002) Ginkgo biloba extract: cognitive enhancer or antistress buffer. Pharmacol Biochem Behav 72(4):913–922

    Article  PubMed  CAS  Google Scholar 

  • Wasilewski M, Wojtczak L (2005) Effects of N-acylethanolamines on the respiratory chain and production of reactive oxygen species in heart mitochondria. FEBS Lett 579(21):4724–4728

    Article  PubMed  CAS  Google Scholar 

  • Weinberger NM (2006) Food for thought: honeybee foraging, memory, and acetylcholine. Sci STKE 2006(336):pe23

  • Williams MD, Van Remmen H, Conrad CC, Huang TT, Epstein CJ, Richardson A (1998) Increased oxidative damage is correlated to altered mitochondrial function in heterozygous manganese superoxide dismutase knockout mice. J Biol Chem 273(43):28510–28515

    Article  PubMed  CAS  Google Scholar 

  • Williamson G, Barron D, Shimoi K, Terao J (2005) In vitro biological properties of flavonoid conjugates found in vivo. Free Radic Res 39(5):457–469

    Article  PubMed  CAS  Google Scholar 

  • Wills ED (1966) Mechanisms of lipid peroxide formation in animal tissues. Biochem J 99(3):667–676

    PubMed  CAS  Google Scholar 

  • Worthington DJ, Rosemeyer MA (1974) Human glutathione reductase: purification of the crystalline enzyme from erythrocytes. Eur J Biochem 48(1):167–177

    Article  PubMed  CAS  Google Scholar 

  • Yao Y, Han DD, Zhang T, Yang Z (2010) Quercetin improves cognitive deficits in rats with chronic cerebral ischemia and inhibits voltage-dependent sodium channels in hippocampal CA1 pyramidal neurons. Phytother Res 24(1):136–140

    Article  PubMed  CAS  Google Scholar 

  • Yasui M, Kihira T, Ota K (1992) Calcium, magnesium and aluminum concentrations in Parkinson’s disease. Neurotoxicology 13(3):593–600

    PubMed  CAS  Google Scholar 

  • Zatta P, Ibn-Lkhayat-Idrissi M, Zambenedetti P, Kilyen M, Kiss T (2002) In vivo and in vitro effects of aluminum on the activity of mouse brain acetylcholinesterase. Brain Res Bull 59(1):41–45

    Article  PubMed  CAS  Google Scholar 

  • Zumkley H, Bertram HP, Lison A, Knoll O, Losse H (1979) AI, Zn and Cu concentrations in plasma chronic renal insufficiency. Clin Nephrol 12:18–21

    PubMed  CAS  Google Scholar 

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Acknowledgments

The financial assistance provided to Deep Raj Sharma, Willayat Yousuf Wani and Deepika Verma by Indian Council of Medical Research, New Delhi, India is greatly acknowledged. The financial assistance provided to Aditya Sunkaria by Council of Scientific and Industrial Research, New Delhi, India is greatly acknowledged.

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Sharma, D.R., Wani, W.Y., Sunkaria, A. et al. Quercetin Protects Against Chronic Aluminum-Induced Oxidative Stress and Ensuing Biochemical, Cholinergic, and Neurobehavioral Impairments in Rats. Neurotox Res 23, 336–357 (2013). https://doi.org/10.1007/s12640-012-9351-6

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