Quercetin and Omega 3 Ameliorate Oxidative Stress Induced by Aluminium Chloride in the Brain

Abstract

Exposure to high levels of aluminum (Al) leads to neurodegeneration, which may be mediated through over-generation of free radicals. So, in the present study, we investigated the ability of both quercetin and omega 3 to ameliorate adverse effects of Al on brain antioxidants by monitoring the main brain antioxidant enzymes on molecular and cellular levels. The obtained results indicated that Al induced oxidative stress through induction of free radical production and inhibition of activity and expression of the antioxidant enzymes catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx); and at the same time induced superoxide dismutase (SOD) activity and gene expression. Both quercetin (QE) and omega 3 have the ability to overcome Al-induced oxidative stress, manifested by the significant reduction in free radical concentration and induction of the activity and gene expression of the brain antioxidant enzymes.

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References

  1. Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    CAS  PubMed  Article  Google Scholar 

  2. Anane R, Creppy EE (2001) Lipid peroxidation as pathway of aluminium cytotoxicity in human skin fibroblast cultures: prevention by superoxide dismutase + catalase and vitamins E and C. Hum Exp Toxicol 20:477–481

    CAS  PubMed  Article  Google Scholar 

  3. Atienzar F, Desor D, Burnel D, Keller JM, Lehr P, Vasseur P (1998) Effect of aluminum on superoxide dismutase activity in the adult rat brain. Biol Trace Elem Res 65(1):19–30

    CAS  PubMed  Article  Google Scholar 

  4. Becaria A, Campbell A, Bondy SC (2002) Aluminum as a toxicant. Toxicol Ind Health 18:309–320

    CAS  PubMed  Article  Google Scholar 

  5. Benzi G, Marzatico F, Pastoris O, Villa RF (1989) Relationship between aging, drug treatment and the cerebral enzymatic antioxidant system. Exp Gerontol 24:137–148

    CAS  PubMed  Article  Google Scholar 

  6. Beutler E (1969) Effect of flavin compounds on the glutathione reductase activity: in vivo and in vitro studies. J Clin Invest 48:1957–1966

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  7. Bondy SC, Kirstein S (1996) The promotion of iron-induced generation of ROS in nerve tissue by aluminium. Mol Chem Neuropathol 27:185–194

    CAS  PubMed  Article  Google Scholar 

  8. Bronner C, Landry Y (1985) Kinetics of the inhibitory effect of flavonoids on histamine secretion from mast cells. Agents Actions 16:147–151

    CAS  PubMed  Article  Google Scholar 

  9. Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310

    CAS  PubMed  Article  Google Scholar 

  10. Cho JY, Kim IS, Jang YH, Kim AR, Lee SR (2006) Protective effect of quercetin, a natural flavonoid against neuronal damage after transient global cerebral ischemia. Neurosci Lett 404(3):330–335

    CAS  PubMed  Article  Google Scholar 

  11. Davis W, Lamson MS, Mattew S, Brignall ND (2000) Antioxidants and cancer III: qurecetin. Alternat Med Rev 5(3):196–208

    Google Scholar 

  12. Deloncle R, Huguet F, Babin P, Fernandez B, Quellard N, Guillard O (1999) Administration of aluminum L-glutamate in young mature rats: effects on iron levels and lipid peroxidation in selected brain areas. Toxicol Lett 104:65–73

    CAS  PubMed  Article  Google Scholar 

  13. De-Whalley C, Rankin SM, Houct JRS, Jessup W, Leake DS (1990) Flavonoids inhibit the oxidative modification of low-density lipoproteins by macrophages. Biochem Pharmacol 39:1743–1750

    CAS  PubMed  Article  Google Scholar 

  14. Dizdaroglu M, Jaruga P, Birincioglu M, Rodriguez H (2002) Free radical-induced damage to DNA; mechanisms and measurement. Free Radic Biol Med 32(11):1102–1115

    CAS  PubMed  Article  Google Scholar 

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

    PubMed  Google Scholar 

  16. Dua R, Gill KD (2001) Aluminum phosphide exposure: implications on rat brain lipid peroxidation and antioxidant defence system. Pharmacol Toxicol 89:315–319

    CAS  PubMed  Article  Google Scholar 

  17. Ellen YY, Guo-Ross SS, Bondy SC (1999) The stabilization of ferrous iron by a toxic b-amyloid fragment and by an aluminum salt. Brain Res 839:221–226

    Article  Google Scholar 

  18. Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 17:214–226

    Google Scholar 

  19. Erasmus RT, Kusnir J, Stevenson WC, Lobo P, Herman MM, Wills MR, Julka J, Gill KD (1996) Effect of aluminum on regional brain antioxidant defense status in Wistar rats. Res Exp Med (Berl) 196:187–194

    Article  Google Scholar 

  20. Ferretti G, Marchionni C, Bacchetti T, Galeazzi T, Dousset N (2003) Effect of aluminum on lipid peroxidation of human high density lipoproteins. Free Radic Res 37:515–521

    CAS  PubMed  Article  Google Scholar 

  21. Fiorani M, De Sanctis S, Menghinello P, Cucchiarini L, Cellini B, Dacha M (2001) Quercetin prevents glutathionedepletion induced by dehydroascorbic acid in rabbit red blood cells. Free Radic Res 34(6):639–648

    CAS  PubMed  Article  Google Scholar 

  22. Fleming J, Josh JG (1987) Ferritin: isolation of aluminium-ferritincomplex from brain. Proc Natl Acad Sci USA 84:7866–7870

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  23. Gonzalez-Muñoz MJ, Meseguer I, Sanchez-Reus MI, Schultz A, Olivero R, Benedí J et al (2008) Beer consumption reduces cerebral oxidation caused by aluminum toxicity by normalizing gene expression of tumor necrotic factor alpha and several antioxidant enzymes. Food Chem Toxicol 46:1111–1118

    PubMed  Article  Google Scholar 

  24. Good PF, Werner P, Hsu A, Olanow CW, Perl DP (1996) Evidence for neuronal oxidative damage in Alzheimer’s disease. Am J Pathol 140:621–628

    Google Scholar 

  25. Gupta A, Shukla GS (1995) Effect of chronic aluminum exposure on the levels of conjugated dienes and enzymatic antioxidants in hippocampus and whole brain of rat. Bull Environ Contam Toxicol 55(5):716–722

    CAS  PubMed  Article  Google Scholar 

  26. Gutteridge JMC, Quinlan GJ, Clark I, Halliwell B (1985) Aluminium salts accelerate peroxidation of membrane lipids stimulated by iron salts. Biochem Biophys Acta 835:441–447

    CAS  PubMed  Article  Google Scholar 

  27. Heo HJ, Lee CY (2004) Protective effects of quercetin and vitamin C against oxidative stress-induced neurodegeneration. J Agric Food Chem 52:7514–7

    Google Scholar 

  28. Hollman PCH, Trijp JMP, Buysman MNCP (1997) Bioavailability of the dietary antioxidant flavonol quercetin in man. Cancer Lett 114:139–140

    CAS  PubMed  Article  Google Scholar 

  29. Hui L, Lei Z, Shaoping LU (2012) Evaluation of antioxidant and immunity activities of quercetin in isoproterenol-treated rats. Molecules 17:4281–4291

    Article  Google Scholar 

  30. Julka D, Gill KD (1996) Altered calcium homeostasis: a possible mechanism of aluminium-induced neurotoxicity. Biochim Biophys Acta 1315:47–54

    PubMed  Article  Google Scholar 

  31. Kim MS, Lee JI, Lee WY, Kim SE (2004) Neuroprotective effect of Ginkgo biloba L. extract in a rat model of parkinson’s disease. Phytother Res 18(8):663–666

    CAS  PubMed  Article  Google Scholar 

  32. Lawrence RA, Burk RF (1979) Glutathione peroxidase activity in seleniumdeficient rat liver. Biochem Biophys Res Commun 71:952–958

    Article  Google Scholar 

  33. Lukiw WJ, Pogue AI (2007) Induction of specific micro RNA (miRNA) species by ROS-generating metal sulfates in primary human brain cells. J Inorg Biochem 101:1265–1269

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  34. Mahesh T, Menon VP (2004) Quercetin allievates oxidative stress in streptozotocin-induced diabetic rats. Phytother Res 18(2):123–127

    CAS  PubMed  Article  Google Scholar 

  35. Meadus WJ (2003) A semi-quantitative RT-PCR method to measure the in vivo effect of dietary conjugated linoleic acid on protein muscle PPAR gene expression. Biol Proc Online 5(1):20–28

    CAS  Article  Google Scholar 

  36. Moyer TP (1999) Toxic metals. In: Burtis CA, Ashwood ER (eds) Tietz textbook of clinical chemistry, 3rd edn. W.B. Saunders Co, Philadelphia, pp 982–998

    Google Scholar 

  37. Newairy AS, Salama AF, Hussien HM, Yousef MI (2009) Propolis alleviates aluminium-induced lipid peroxidation and biochemical parameters in male rats. Food Chem Toxicol 47(6):1093–1098

    CAS  PubMed  Article  Google Scholar 

  38. Nirmala RN, Shankarbhat K, Urban D (2013) Effect of long term administration of aluminum chloride on oxidative stress and acetylcholinesterase activity in rat brains. IJPBS 3(1):616–622

    Google Scholar 

  39. Olga B, Sergueï S, Véronique L, Jean MF, Saúl V (2010) Transl an approach to the study of gene expression in hepatocarcinogenesis initiation. Oncol 3(2):142–148

    Google Scholar 

  40. Omer C, Mehmet K, Ferah A, Kuriulus C, Betul K, Omer Y (2004) Protective effects of quercetin, a flavonoid antioxidant, in absolute ethanol-induced acute gastric ulcer. Eur J Gen Med 1(3):37–42

    Google Scholar 

  41. Pournourmohammadi S, Khazaeli P, Eslamizad S, Tajvar A, Mohammadirad A, Abdollahi M (2008) Study on the oxidative stress status among cement plant workers. Hum Exp Toxicol 27:463–469

    CAS  PubMed  Article  Google Scholar 

  42. Pratico D, Uryu K, Sung S, Tang S, Trojanowski JQ, Lee VMY (2002) Aluminium modulates brain amyloidosis through oxidative stress in APP transgenic mice. FASEB J 16:1138–1140

    CAS  PubMed  Google Scholar 

  43. Pu F, Mishima K, Irie K (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

    CAS  PubMed  Article  Google Scholar 

  44. Ribes D, Colomina MT, Vicens P, Domingo JL (2008) Effects of oral aluminium exposure on behavior and neurogenesis in a transgenic mouse model of Alzheimer’s disease. Exp Neural 214:293–300

    CAS  Article  Google Scholar 

  45. Robert LMS, Duncan CSE, O’Keefe WF, Eigel N (2009) Antioxidant Protection of an Omega-3 Fatty Acid Fortified Dairy-Based Beverage, Thesis submitted to the faculty of the Virginia Polytechnic Institute and State University in partial fulfillment of the requirements for the degree of Masters of Science In Food Science and Technology Blacksburg

  46. Satyendra SB, Nikhil S, Rajendra SB, Preeti A, Sarlesh R (2012) A review of quercetin: antioxidant and anticancer properties. World J Pharm Pharmaceut Sci 1(1):146–160

    Google Scholar 

  47. Sharma P, Ahmad SZ, Kumar A, Islam F, Mishra KP (2007) Role of combined administration of Tiron and glutathione against aluminum-induced oxidative stress in rat brain. J Trace Elem Med Biol 21:63–70

    CAS  PubMed  Article  Google Scholar 

  48. Shati AA, Elsaid FG, Hafez EE (2011) Biochemical and molecular aspects of aluminium chloride-induced neurotoxicity in mice and the protective role of Crocus sativus L. extraction and honey syrup. Neuroscience 175:66–74

    CAS  PubMed  Article  Google Scholar 

  49. Steven RM, David CN, Masha F, Valerie D, Lisa SM, Dru AH, Fuxia J, Michael JL (2010) Effect of n-3 fatty acids and antioxidants on oxidative stress after exercise. Med Sci Sports Exerc 42(9):1704–1711

    Article  Google Scholar 

  50. Swain C, Chainy GB (1997) Aluminum effect on lipid peroxidation and on the activities of superoxide dismutase and catalase in the cerebral hemisphere and liver of young chicks. J Trace Elem Med Biol 11(2):77–82

    CAS  PubMed  Article  Google Scholar 

  51. Vauzour D, Vafeiadou K, Rodriguez-Mateos A (2008) The neuroprotective potential of flavonoids: a multiplicity of effects. Genes Nutr 3:115–126

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  52. Veer BG, Anithaa S, Hegdea ML, Zecca L, Garruto RM, Ravid R, Shankar SK, Stein R, Shanmugavelu P, Jagannatha KS (2005) Aluminium in Alzheimer’s disease: are we still at a crossroad? Cell Mol Life Sci 62:143–158

    Article  Google Scholar 

  53. Xu F, Fok TF, Yung E, Yin JA, To KF (2000) Antioxidant enzyme activities and antioxidant enzyme gene expression in hyperoxia-induced lung injury in premature rat. HK J Paediatr 5:3–7

    Google Scholar 

  54. Youdim KA, Qaiser MZ, Begley DJ, Rice-Evans CA, Abbott NJ (2004) Flavonoid permeability across an in situ model of the blood brain barrier. Free Radic Biol Med 36(5):592–604

    CAS  PubMed  Article  Google Scholar 

  55. Yousef MI (2004) Aluminium-induced changes in hemato- biochemical parameters, lipid peroxidation and enzyme activities of male rabbits: protective role of ascorbic acid. Toxicology 199:47–57

    CAS  PubMed  Article  Google Scholar 

  56. Zatta P, Kiss T, Suwalsky M, Berthon G (2002) Aluminum as a promoter of cellular oxidation. Coord Chem Rev 228:271–284

    CAS  Article  Google Scholar 

  57. Zattal PF, Nicolini M, Corain B (1991) Aluminium (III) toxicity and blood-brain barrier permeability. In: Aluminium in chemistry, biology and medicine. Cortina International, Verona and Reven Press, New York, pp 97–112

    Google Scholar 

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Correspondence to Mohamed Afifi.

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Ali, H.A., Afifi, M., Abdelazim, A.M. et al. Quercetin and Omega 3 Ameliorate Oxidative Stress Induced by Aluminium Chloride in the Brain. J Mol Neurosci 53, 654–660 (2014). https://doi.org/10.1007/s12031-014-0232-8

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Keywords

  • Aluminum
  • Brain antioxidants
  • Quercetin
  • Omega 3