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Biological Trace Element Research

, Volume 165, Issue 1, pp 67–74 | Cite as

Protective Effect of Selenium Against Aluminum Chloride-Induced Alzheimer’s Disease: Behavioral and Biochemical Alterations in Rats

  • B. V. S. LakshmiEmail author
  • M. Sudhakar
  • K. Surya Prakash
Article

Abstract

In present study, selenium was selected for evaluating effect of selenium on aluminum chloride (AlCl3)-induced Alzheimer’s disease in rats. Thirty Wistar rats were divided into five groups of six in each. Group I (control) received distilled water, group II—AlCl3 (100 mg/kg, p.o.), group III—selenium (1 mg/kg, p.o.), group IV—AlCl3 + vitamin E (100 mg/kg, p.o. + 100 mg/kg, p.o.), and group V—AlCl3 + selenium (100 mg/kg, p.o. + 1 mg/kg, p.o.) for 21 days. At end of experiment, various behavioral, biochemical, and histopathological assessments were carried out. The animals showed increase in time to reach platform in Morris water maze and decreased step-down latencies in passive avoidance test indicating learning and memory impairment in aluminum chloride-treated group, but administration of selenium decreased time to reach platform in Morris water maze, increased step-down latencies, and strengthened its memory action in drug-treated animals. There was decrease in muscle strength measured by rotarod test indicating motor incoordination and decrease in locomotor activity assessed by actophotometer test in AlCl3 control group, whereas in selenium–AlCl3 group, there was improvement in muscle strength and locomotion. Biochemical analysis of the brain revealed that chronic administration of AlCl3 significantly increased lipid peroxidation and decreased levels of acetyl cholinesterase, catalase, reduced glutathione and glutathione reductase, an index of oxidative stress process. Administration of selenium attenuated lipid peroxidation and ameliorated the biochemical changes. There were marked changes at subcellular level observed by histopathology studies in AlCl3 group, and better improvement in these changes was observed in selenium + AlCl3group. Therefore, this study strengthens the hypothesis that selenium helps to combat oxidative stress produced by accumulation of AlCl3 in the brain and helps in prophylaxis of Alzheimer’s diseases.

Keywords

Alzheimer’s disease Acetyl cholinesterase Morris water maze Locomotor activity Passive avoidance test 

Abbreviations

kg

kilogram

mg

Milligram

ml

Milliliter

p.o

Per oral

AD

Alzheimer’s disease

SDL

Step-down latency

PMSF

Phenyl methyl sulfonylfluoride

AChE

Acetyl cholinesterase

EDTA

Ethylene diamine-tetra-acetic acid

Alcl3

Aluminum chloride

DTNB

Dithiobis nitrobenzoic acid

Se

Selenium

Notes

Acknowledgments

The authors are thankful to the authorities of Malla Reddy College of Pharmacy, Secunderabad, for providing support to this study.

Conflict of Interest

All the authors declare that there are no competing financial interests in relation to the work, and it was not funded by any organizations.

References

  1. 1.
    Kimura R, Ohno M (2009) Impairments in remote memory stabilization precede hippocampal synaptic and cognitive failures in 5XFAD Alzheimer mouse model. Neurobiol Dis 33:229–235CrossRefPubMedCentralPubMedGoogle Scholar
  2. 2.
    Zhu X, Perry G, Moreira PI, Aliev G, Cash AD, Hirai K, Smith MA (2006) Mitochondrial abnormalities and oxidative imbalance in Alzheimer disease. J Alzheimers Dis 9:147–153PubMedGoogle Scholar
  3. 3.
    Sommer B (2002) Alzheimer’s disease and the amyloid cascade hypothesis: ten years on. Curr Opin Pharmacol 2:87–92CrossRefPubMedGoogle Scholar
  4. 4.
    Sun Z-Z (2009) Alteration of Aß metabolism-related molecules in predementia induced by AlCl3 and D-galactose. Age 31:277–284CrossRefPubMedCentralPubMedGoogle Scholar
  5. 5.
    Walton JR (2007) An aluminum-based rat model for Alzheimer’s disease exhibits oxidative damage, inhibition of PP2A activity, hyperphosphorylated tau, and granulovacuolar degeneration. J Inorg Biochem 101:1275–1284CrossRefPubMedGoogle Scholar
  6. 6.
    Shuchang H, Qiao N, Piye N et al (2008) Protective effects of gastrodiaelata on aluminium chloride-induced learning impairments and alterations of amino acid neurotransmitter release in adult rats. Restor Neurol Neurosci 26:467–473PubMedCentralPubMedGoogle Scholar
  7. 7.
    Kakkar V, Kaur IP (2011) Evaluating potential of curcumin loaded solid lipid nanoparticles in aluminium induced behavioural, biochemical and histopathological alterations in mice brain. Food Chem Toxicol 49:2906–2913CrossRefPubMedGoogle Scholar
  8. 8.
    Miller S, Walker SW, Arthur JR, Nicol F, Pickard K et al (2001) Selenite protects human endothelial cells from oxidative damage and induces thioredoxin reductase. Clin Sci 100:543–550CrossRefPubMedGoogle Scholar
  9. 9.
    El-Demerdash FM (2004) Antioxidant effect of vitamin E and selenium on lipid peroxidation, enzyme activities and biochemical parameters in rats exposed to aluminium. J Trace Elem Med Biol 18:113–122CrossRefPubMedGoogle Scholar
  10. 10.
    Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160:1–4CrossRefPubMedGoogle Scholar
  11. 11.
    Fengyuan W, Gang S, Jing F, Keijie C et al (2013) Protective effects of sodium selenite against aflatoxin B1-induced oxidative stress and apoptosis in broiler spleen. Int J Environ Res Public Health 10(7):2834–2844CrossRefGoogle Scholar
  12. 12.
    Punitha B, ML G, DK D (2010) Protective role of lithium during aluminium-induced neurotoxicity. Neurochemistry Internat 56:256–262CrossRefGoogle Scholar
  13. 13.
    Ataie A, Sabetkassaei M, Haghparast A, Moghaddam A, Alaee R, Sn M (2010) Curcumin exerts neuroprotective effects against homocysteine intracerebroventricular injection-induced cognitive impairment and oxidative stress in rat brain. J Med Food 13(4):821–826CrossRefPubMedGoogle Scholar
  14. 14.
    Thirunavukkarasu SV, Upadhyay L, Venkataraman S (2012) Effect of Manasamitra vatakam, an Ayurvedic formulation, on aluminim-induced neurotoxicity in rats. Tropical J Pharm Res 11(1):75–83Google Scholar
  15. 15.
    Nwanjo HU, Ojiako OA (2005) Effect of vitamins E and C on exercise induced oxidative stress. Global J Pure Appl Sci 12:199–202Google Scholar
  16. 16.
    Aebi HE (1993) Catalase. In: Bergmeyer HU, Bergmeyer J, Grabl M (eds) Methods of enzymatic analysis, vol 3. Velag Chemie Gmbh, Weinheim, pp 273–286Google Scholar
  17. 17.
    Ellman GC (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77CrossRefPubMedGoogle Scholar
  18. 18.
    Hafeman DG, Sunde RA, Hoekstra WG (1974) Effect of dietary selenium on erythrocyte and liver glutathione peroxidase in the rat. J Nutr 104:580–587PubMedGoogle Scholar
  19. 19.
    Kumar A, Dogra S, Prakash A (2009) Effect of carvedilol on behavioral, mitochondrial dysfunction, and oxidative damage against D-galactose induced senescence in mice. Naunyn Schmiedebergs Arch Pharmacol 380:431–441CrossRefPubMedGoogle Scholar
  20. 20.
    Campbell A (2002) The potential role of aluminium in Alzheimer’s disease. Nephrol Dial Transplant 17:17–20CrossRefPubMedGoogle Scholar
  21. 21.
    Yokel RA (2000) The toxicology of aluminium in the brain: a review. Neurotoxicol 21:813–828Google Scholar
  22. 22.
    Rabe A, Lee MH, Shek J, Wisniewski HM (1982) Learning deficit in immature rabbits with aluminium-induced neurofibrillary changes. Exp Neurol 76:441–446CrossRefPubMedGoogle Scholar
  23. 23.
    Canales JJ, Corbalán R, Montoliu C, Llansola M, Monfort P, Erceg S, Hernandez-Viadel M, Felipo V (2001) Aluminium impairs the glutamate-nitric oxide-cGMP pathway in cultured neurons and in rat brain in vivo: molecular mechanisms and implications for neuropathology. J Inorg Biochem 87:63–69CrossRefPubMedGoogle Scholar
  24. 24.
    Ghribi O, DeWitt DA, Forbes MS, Aii A, Herman MM, Savory J (2001) Cyclosporin A inhibits Al-induced cytochrome c release from mitochondria in aged rabbits. J Alzheimers Dis 3:387–391PubMedGoogle Scholar
  25. 25.
    Bharathi P, 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 52:275–292CrossRefPubMedGoogle Scholar
  26. 26.
    Yoshioka T, Iwamoto N, Tsukahara F, Irie K, Urakawa I, Muraki T (2000) Anti-NO action of carvedilol in cell-free system and in vascular endothelial cells. Br J Pharmacol 129:1530–1535CrossRefPubMedCentralPubMedGoogle Scholar
  27. 27.
    Maèièkova T, Peèivova J, Nosal R, Holomanova D (2005) Influence of carvedilol on superoxide generation and enzyme release from stimulated human neutrophils. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 149:389–392CrossRefGoogle Scholar
  28. 28.
    Germano C, Kinsella GJ (2005) Working memory and learning in early Alzheimer’s disease. Neuropsychol Rev 15:1–10CrossRefPubMedGoogle Scholar
  29. 29.
    Kaizer RR, Corrêa MC, Spanevello RM, Morsch VM, Mazzanti CM, Gonçalves JF, Schetinger MR (2005) Acetylcholinesterase activation and enhanced lipid peroxidation after long-term exposure to low levels of aluminum on different mouse brain regions. J Inorg Biochem 99:1865–1870CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • B. V. S. Lakshmi
    • 1
    Email author
  • M. Sudhakar
    • 1
  • K. Surya Prakash
    • 1
  1. 1.Department of PharmacologyMalla Reddy College of PharmacySecunderabadIndia

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