Skip to main content

Advertisement

SpringerLink
Log in

Effect of Resveratrol on Antioxidant Enzyme Activities in the Brain of Healthy Rat

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

We have studied the effect of resveratrol on lipoperoxidation and antioxidant enzyme activity level in the brain of healthy rats. When intraperitoneally administered, resveratrol significantly and dose dependently decreased brain malondialdehyde level. Resveratrol also increased in a dose-dependent way brain superoxide dismutase, catalase and peroxidase activities. Optimal effect on antioxidant enzyme and lipoperoxidation products were obtained with resveratrol concentration of 12.5 mg/kg body wt. Native polyacrylamide gel electrophoresis analysis of antioxidant isoenzymes revealed that resveratrol up regulated at least two acidic superoxide dismutase isoforms called A1 and A2, two basic isoforms called B1 and B2. Resveratrol also up regulated two catalase isoforms and a broad peroxidase band corresponding to several isoforms. All these findings suggest that resveratrol is able to cross the blood brain barrier and exerts potent antioxidant features. Resveratrol also exerts neuroprotective properties by up regulating several detoxifying enzymes, most of which are iron proteins.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Andersen JK (2004) Oxidative stress in neurodegeneration: cause or consequence? Nature Med 10(suppl):S18–S25

    PubMed  Google Scholar 

  2. Fleury C, Mignotte B, Vayssiere JL (2002) Mitochondrial ROS in cell death signalling. Biochimie 84:131–134

    Article  PubMed  CAS  Google Scholar 

  3. Gilgun-sherki Y, Melamed E, Offen D (2001) Oxidative stress induced-neurodegenerative diseases: the need for antioxidants that penetrate the blood brain barrier. Neuropharmacol 40:959–975

    Article  CAS  Google Scholar 

  4. Bradamante S, Barenghi L, Piccinini F, Bertelli AAE, De Jonge R, Beemster P, De Jong JW (2003) Resveratrol provides late-phase cardioprotection by means of a NO and adenosine-mediated mechanism. Eur J Pharmacol 465:115–123

    Article  PubMed  CAS  Google Scholar 

  5. Hsieh TC, Juan GZ, arzynkiewicz ZD, Wu JM (1999) Resveratrol increases nitric oxide synthase, induces accumulation of p53 and p21 (WAF1/CIP1), suppresses cultured bovine pulmonary artery endothelial cell proliferation by perturbing progression through S and G2. Cancer Res 59:2596–2601

    PubMed  CAS  Google Scholar 

  6. Bastianetto S, Zheng WH, Quirion R (2000) Neuroprotective abilities of resveratrol and other red wine constituents against nitric oxide related toxicity in cultured hippocampal neurons. Br J Pharmacol 131:711–720

    Article  PubMed  CAS  Google Scholar 

  7. Bertelli AAE, Giovannini L, Giannessi D, Migliori M, Bernini W, Fregoni M, Bertelli A (1995) Anti-platelet activity of synthetic and natural resveratrol in red wine. Int J Tiss Reac 17:1–3

    CAS  Google Scholar 

  8. Belguendouz L, Frémont L, Gozzelino MT (1998) Interaction of transresveratrol with plasma lipoproteins. Biochem Pharmacol 55: 811–816

    Article  PubMed  CAS  Google Scholar 

  9. Huang C, Ma WY, Goranson A, Dong Z (1999) Resveratrol suppress cell transformation and induces apoptosis through a P53-dependent pathway. Carcinogenesis 20:237–242

    Article  PubMed  CAS  Google Scholar 

  10. Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CWW, Fong HHS, Farsworth NR, Kinghorn AD, Mehta RG, Moon RC, Pezzuto JM (1997) Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275:218–220

    Article  PubMed  CAS  Google Scholar 

  11. Gehm BD, McAndrews JM, Chien PY, Jameson JL (1997) Resveratrol, a polyphenolic compound found in grapes and wine is an agonist for the oestrogen receptor. Proc Natl Acad Sci USA 94:14138–14143

    Article  PubMed  CAS  Google Scholar 

  12. Ray PS, Maulik G, Cordis GA, Bertelli AAE, Bertelli A, Das DK (1999) The red wine antioxidant resveratrol protects isolated rat hearts from ischemia-reperfusion injury. Free Radic Biol Med 27:160–169

    Article  PubMed  CAS  Google Scholar 

  13. Hung LM, Su MJ, Chen JK (2004) Resveratrol protects myocardial ischemia-reperfusion injury through both NO-dependent and NO-independent mechanisms. Free Radic Biol Med 36:774–781

    Article  PubMed  CAS  Google Scholar 

  14. Araki T, Sasaki Y, Milbrandt J (2004) Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Science 305:1010–1013

    Article  PubMed  CAS  Google Scholar 

  15. Parker AJ, Arango M, Abderrahmane S, Lambert E, Tourette C, Catoire H, Neri C (2005) Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons. Nature Genet 37:349–350

    Article  PubMed  CAS  Google Scholar 

  16. Marambaud P, Zhao H, Davies P (2005) Resveratrol promotes clearance of Alzheimer’s disease amyloid-β-peptides. J Biol Chem 280:37377–37382

    Article  PubMed  CAS  Google Scholar 

  17. Picard F, Kurtev MN, Chung N, Topark-ngarm A, Senawong T, Machado de Oliveira RM, Leid MMW, McBurney MW, Guarente L (2004) SIRT1 promotes fat mobilization in white adipocytes by repressing PPAR-γ. Nature 429:771–776

    Article  PubMed  CAS  Google Scholar 

  18. Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang UU, Scherer B, Sinclair DA (2003) Small molecule activators of sirtuins extend Saccharomyces cerevisae lifespan. Nature 425:191–196

    Article  PubMed  CAS  Google Scholar 

  19. Draper HH, Hadley M (1990) Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 186:421–431

    Article  PubMed  CAS  Google Scholar 

  20. Misra HP, Fridovich I (1972) The role of superoxide anion in autoxidation of epinephrine and a simple assay for SOD. J Biol Chem 247:3170–3175

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  22. Chance B, Maehly AC (1955) Assay of catalases and peroxidases. Methods Enzymol 2:764–817

    Article  Google Scholar 

  23. Davis BJ (1964) Disc electrophoresis II. Method and application to human serum proteins. Ann NY Acad Sci 121:404–427

    Article  PubMed  CAS  Google Scholar 

  24. Reisfeld JC, Lewis UJ, Williams DE (1962) Disk electrophoresis of basic proteins and peptides on polyacrylamide gels. Nature 195:281–283

    Article  PubMed  CAS  Google Scholar 

  25. Beauchamp C, Fridovitch I (1971) Superoxide dismutase: improved assays and an assay applicable to acrylamide gels. Anal Biochem 44:276–287

    Article  PubMed  CAS  Google Scholar 

  26. Loukhili A, Limam F, Ayadi A, Boyer N, Ouelhazi L (1999) Purification and characterization of a neutral peroxidase induced by rubbing tomato internodes. Physiol Plant 105:24–31

    Article  Google Scholar 

  27. Lee DL, Kim YS, Lee CB (2001) The inductive responses of the antioxidant enzymes by salt stress in the rice (Oryza sativa L). J Plant Physiol 158:737–745

    Article  CAS  Google Scholar 

  28. Woodburry W, Spencer AK, Stahmann MA (1971) An improved procedure using ferricyanide for detecting catalase isoenzymes. Anal Biochem 44:301–305

    Article  Google Scholar 

  29. Ohnishi ST, Barr JK (1978) A simple method of quantitating protein using the biuret and phenol reagent. Anal Biochem 86:193–200

    Article  PubMed  CAS  Google Scholar 

  30. Maccarone M, Lorenzon T, Guerrieri P, Finazziagro A (1999) Resveratrol prevents apoptosis in K562 cells by inhibiting lipoxygenase and cyclooxygenas activity. FEBS J 265:27–33

    Google Scholar 

  31. Juan SH, Cheng TH, Lin HC, Chu YL, Lee WS (2005) Mechanism of concentration-dependent induction of heme oxygenase-1 by resveratrol in human aortic smooth muscle cells. Biochem Pharmacol 69:41–48

    Article  PubMed  CAS  Google Scholar 

  32. Zhuang H, Kim YS, Koehler RC, Dore S (2003) Potential mechanism by which resveratrol, a red wine constituent, protects neurons. Ann NY Acad Sci 993:276–286

    Article  PubMed  CAS  Google Scholar 

  33. Kasdallah-Grissa A, Mornagui B, Aouani E, Hammami M, Gharbi N, Kamoun A, El-fazaa S (2006) Protective effect of resveratrol on ethanol-induced lipid peroxidation in rats. Alcohol. Alcohol 41:236–239

    CAS  Google Scholar 

  34. Han YS, Bastianetto S, Dumont Y, Quirion R (2006) Specific plasma membrane binding sites for polyphenols, including resveratrol, in the rat brain. J Pharmacol Exp Ther 318:238–245

    Article  PubMed  CAS  Google Scholar 

  35. Juan ME, Vinardel MP, Planas JM (2002) The daily oral administration of high doses of resveratrol to rats for 28 days is not harmful. J Nutr 132:257–260

    PubMed  CAS  Google Scholar 

  36. Peng J, Stevenson FF, Doctrow SR, Andersen JK (2005) Superoxide dismutase/catalase mimetics are neuroprotective against selective paraquat-mediated dopaminergic neuron death in the substantial nigra. J Biol Chem 280:29194–29198

    Article  PubMed  CAS  Google Scholar 

  37. Schriner SE, Linford NJ, Martin GM, Trenting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308:1909–1911

    Article  PubMed  CAS  Google Scholar 

  38. Ralph GC, Radcliffe PA, Day DM, Mcarthy J, Leroux MA, Lee DCP, Wong LF, Bilsland LG, Greensmith L, Mckingsman S, Mitrophanous KA, Mazarakis ND, Azzouz M (2005) Silencing mutant SOD1 using RNAi protects against neurodegeneration and extends survival in an ALS model. Nature Med 11:429–433

    Article  PubMed  CAS  Google Scholar 

  39. Santos MJ, Quintanilla RA, Toro A, Grandy R, Dinamarca MC, Godoy JA, Inestrosa NC (2005) Peroxisomal proliferation protects from β amyloid neurodegeneration. J Biol Chem 28:41057–41068

    Article  CAS  Google Scholar 

  40. Wang Q, Yu S, Simonyi A, Rottinghaus G, Sun GY, Sun AY (2004) Resveratrol protects against neurotoxicity induced by kainic acid. Neurochem Res 29:2105–2112

    Article  PubMed  CAS  Google Scholar 

  41. Jiang ZG, Maylu XC, Nelson V, Yang X, Pau W, Chen RW, Lebowitz MS, Almassain B, Tortella FC, Brady RO, Ghanbari HA (2006) A multifunctional cytoprotective agent that reduces neurodegeneration after ischemia. Proc Natl Acad Sci USA 103:1581–1586

    Article  PubMed  CAS  Google Scholar 

  42. Connor JR (1994) Iron acquisition and expression of iron regulatory proteins in the developing brain: manipulation by ethanol exposure, iron deprivation and cellular dysfunction. Dev Neurosci 16:233–247

    PubMed  CAS  Google Scholar 

  43. Pham CG, Bubici C, Zazzeroni F, Papa S, Jones J, Alvarez K, Jayawardena S, De Smaele E, Cong R, Beaumont C, Torti FM, Torti VS, Franzoso G (2004) ferritin heavy chain upregulation by NF-κB inhibits TNFα-induced apoptosis by suppressing reactive oxygen species. Cell 119:529–542

    Article  PubMed  CAS  Google Scholar 

  44. Puig S, Askeland E, Thiele DJ (2005) Coordinated remodelling of cellular metabolism during iron deficiency through targeted mRNA degradation. Cell 120:99–110

    Article  PubMed  CAS  Google Scholar 

  45. Kaur D, Yantiri F, Rajagopalan S, Kumar J, Mo JQ, Boonplueang R, Viswanath V, Jacobs R, Yang L, Beal MF, DiMonte D, Volitaskis I, Ellerby L, Cherny RA, Bush AI, Andersen JK (2003) Genetic or pharmacological iron chelation prevents MPTP induced neurotoxicity in vivo: a novel therapy for Parkinson’s disease. Neuron 37:899–909

    Article  PubMed  CAS  Google Scholar 

  46. Cherny RA, Atwood CS, Xilinas ME, Gray DN, Jones WD, McLean CA, Barnham KJ, Volitakis I, Fraser FW, Kim Y, Huang X, Goldstein LE, Moir RD, Lim JT, Beyreuther K, Zheng H, Tanzi RE, Masters CL, Bush AI (2001) Treatment with a copper–zinc chelator markedly and rapidly inhibits beta amyloid accumulation in Alzheimer’s disease transgenic mice. Neuron 30:665–676

    Article  PubMed  CAS  Google Scholar 

  47. Nguyen T, Hamby A, Massa SM (2005) Clioquinol down-regulates mutant huntingtin expression in vitro and mitigates pathology in a Huntington’s disease mouse model. Proc Natl Acad Sci USA 102:11840–11845

    Article  PubMed  CAS  Google Scholar 

  48. Ding I, Liu B, Vaught JL, Yamauchi H, Lind SE (2005) Anticancer activity of the antibiotic clioquinol. Cancer Res 65:3389–3395

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Financial support of the Tunisian Ministry of research is gratefully acknowledged. The authors thank R. Ben Kram for expert technical assistance.

Author information

Authors and Affiliations

  1. Laboratoire de Physiologie de la Nutrition, Faculté des Sciences de Tunis, Campus Universitaire El Manar II, 2092, Tunis, Tunisia

    Meherzia Mokni & Mohamed Amri

  2. Laboratoire Interactions Légumineuses-Microorganismes, Centre de Biotechnologie, Technopole Bordj-Cedria, BP-901, 2050, Hammam-Lif, Tunisia

    Salem Elkahoui, Ferid Limam & Ezzedine Aouani

Authors
  1. Meherzia Mokni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Salem Elkahoui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ferid Limam
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mohamed Amri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ezzedine Aouani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ezzedine Aouani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mokni, M., Elkahoui, S., Limam, F. et al. Effect of Resveratrol on Antioxidant Enzyme Activities in the Brain of Healthy Rat. Neurochem Res 32, 981–987 (2007). https://doi.org/10.1007/s11064-006-9255-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-006-9255-z

Keywords

Search

Navigation