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Immediate and Delayed Treatments with Curcumin Prevents Forebrain Ischemia-Induced Neuronal Damage and Oxidative Insult in the Rat Hippocampus

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Abstract

Oxidative stress is believed to contribute to neurodegeneration following ischemic injury. The present study was undertaken to evaluate the possible antioxidant neuroprotective effect of curcumin (Cur) on neuronal death of hippocampal CA1 neurons following transient forebrain ischemia in rat. Treatment of Cur (200 mg/kg/day, i.p.) at three different times (immediately, 3 h and 24 h after ischemia) significantly (P<0.01) reduced neuronal damage 7 days after ischemia. Also, treatment of ischemic rats with Cur decreased the elevated levels of MDA and increased GSH contents, catalase and SOD activities to normal levels. In the in vitro, Cur was as potent as antioxidant (IC50 = 1 μM) as butylated hydroxytoluene. The present study demonstrates that curcumin treatment attenuates forebrain ischemia-induced neuronal injury and oxidative stress in hippocampal tissue. Thus treatment with curcumin immediately or even delayed until 24 h may have the potential to be used as a protective agent in forebrain ischemic insult in human.

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References

  1. Feigin VL, Lawes CMM, Bennett DA, Anderson CS (2003) Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century. The Lancet Neurol 2:43–53

    Article  Google Scholar 

  2. Wolfe CD (2000) The impact of stroke. Br Med Bull 56:275–286

    Article  PubMed  CAS  Google Scholar 

  3. Colbourne F, Li H, Buchan AM, Clemens JA (1999) Continuing postischemic neuronal death in CA1: influence of ischemia duration and cytoprotective doses of NBQX and SNX-111 in rats. Stroke 30:662–668

    PubMed  CAS  Google Scholar 

  4. Rami A, Agarwal R, Botez G, Winckler J (2000) mu-Calpain activation, DNA fragmentation, and synergistic effects of caspase and calpain inhibitors in protecting hippocampal neurons from ischemic damage. Brain Res 866:299–312

    Article  PubMed  CAS  Google Scholar 

  5. Barber PA, Auer RN, Buchan AM, Sutherland GR (2001) Understanding and managing ischemic stroke. Can J Physiol Pharmacol 79:283–296

    Article  PubMed  CAS  Google Scholar 

  6. Candelario-Jalil E, Ajamieh HH, Sam S, Martínez G, Leon OS (2000) Nimesulide limits kainate-induced oxidative damage in the rat hippocampus. Eur J Pharmacol 39:295–298

    Article  Google Scholar 

  7. Liu PK, Grossman RG, Hsu CY, Robertson CS (2001) Ischemic injury and faulty gene transcripts in the brain. Trends Neurosci 24:581–588

    Article  PubMed  CAS  Google Scholar 

  8. Candelario-Jalil E, Mhadu NH, Ai-Dalain SM, Martínez G, Leon OS (2001) Time course of oxidative damage in different brain regions following transient cerebral ischemia in gerbils. Neurosci Res 41:233–241

    Article  PubMed  CAS  Google Scholar 

  9. Chan PH (1996) Role of oxidants in ischemic brain damage. Stroke 27:1124–1129

    PubMed  CAS  Google Scholar 

  10. Reddy AP, Lokesh BR (1994) Effect of dietary turmeric (Curcuma longa) on iron-induced lipid peroxidation in the rat liver. Food Chem Toxicol 32:279–283

    Article  PubMed  CAS  Google Scholar 

  11. Araujo CC, Leon LL (2001) Biological activities of Curcuma longa L. Mem Inst Oswaldo Cruz 96:723–728

    Article  PubMed  CAS  Google Scholar 

  12. Zhao BL, Li XJ, He RG, Cheng SJ, Xin WJ (1989) Scavenging effect of extracts of green tea and natural antioxidants on active oxygen radicals. Cell Biophys 14:175–185

    PubMed  CAS  Google Scholar 

  13. Li JK, Lin-shia SY (2001) Mechanisms of cancer chemoprevention by curcumin. Proc Natl Sci Counc Repub China B 25:59–66

    PubMed  Google Scholar 

  14. Ringman JM, Frautschy SA, Cole GM, Masterman DL, Cummings JLA (2005) Potential role of the curry spice curcumin in Alzheimer’s disease. Curr Alzheimer Res 2:131–136

    Article  PubMed  CAS  Google Scholar 

  15. Cole GM, Lim GP, Yang F, Teter B, Begum A, Ma Q, Harris-White ME, Frautschy SA (2005) Prevention of Alzheimer’s disease: omega-3 fatty acid and phenolic anti-oxidant interventions. Neurobiol Aging 2:133–136

    Article  CAS  Google Scholar 

  16. Huang MT, Newmark HL, Frenkel K (1997) Inhibitory effects of curcumin on tumorigenesis in mice. J Cell Biochem 27:26–34

    Article  CAS  Google Scholar 

  17. Plummer SM, Holloway KA, Manson MM, Munks RJL, Kaptein A, Farrow S, Howells L (1999) Inhibition of cyclo-oxygenase-2 expression in colon cells by the chemoprevention agent curcumin involves inhibition of NF-kappaB activation via the NIK/IKK signaling complex. Oncogene 18:6013–6020

    Article  PubMed  CAS  Google Scholar 

  18. Skrzypczak-Jankun E, McCabe NP, Selman SH, Jankun J (2000) Curcumin inhibits lipoxygenase by binding to its central cavity: theoretical and X-ray evidence. Int J Mol Med 6:521–526

    PubMed  CAS  Google Scholar 

  19. Smith ML, Bendek G, Dahlgren N, Rosen I, Wieloch T, Siesjo BK (1984) Models for studying long-term recovery following forebrain ischemia in the rat, II: a 2-vessel occlusion model. Acta Neurol Scand 69:385–401

    Article  PubMed  CAS  Google Scholar 

  20. Kirino T (1982) Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 239:57–69

    Article  PubMed  CAS  Google Scholar 

  21. Henrich-Noack P, Prehn JHM, Krieglstein J (1996) TGF-β1 protects hippocampal neurons against degeneration caused by transient global ischemia: dose response relationship and potential neuroprotective mechanisms. Stroke 27:1609–1615

    PubMed  CAS  Google Scholar 

  22. Ohkawa H, Ohish N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid. Anal Biochem 95:351–358

    Article  PubMed  CAS  Google Scholar 

  23. Ellman GL (1959) Tissue sulfahydryl groups. Arch Biochem Biophys 82:70–77

    Article  PubMed  CAS  Google Scholar 

  24. Higgins C, Bachner R, McCallster J, Boxer L (1978) Polymorphonucler leukocyte species differences in the disposal of hydrogen peroxide. Proc Soc Exp Biol Med 158:478–481

    PubMed  CAS  Google Scholar 

  25. McCord J, Fridovich I (1969) An enzymatic function for erythrocuprein (Hemocuprein). J Biol Chem 244:6049–6055

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  27. Houghton PJ, Zarka R, de las Heras B, Hoult JR (1995) Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes and membrane lipid peroxidation. Planta Med 61:33–36

    Article  PubMed  CAS  Google Scholar 

  28. Knuckey NW, Palm D, Primiano M, Epstein MH, Johanson CE (1995) N-acetylcysteine enhances hippocampal neuronal survival after transient forebrain ischemia in rats. Stroke 26:305–311

    PubMed  CAS  Google Scholar 

  29. Al Nita D, Nita V, Spulber S, Moldovan M, Popa DP, Zagrean AM, Zagrean L (2001) Oxidative damage following cerebral ischemia depends on reperfusion-a biochemical study in rat. J Cell Mol Med 5:163–170

    Article  PubMed  Google Scholar 

  30. Nanri K, Montecot C, Springhetti V, Seylaz J, Pinard E (1998) The selective inhibitor of neuronal nitric oxide synthase, 7-nitroindazole, reduces the delayed neuronal damage due to forebrain ischemia in rats. Stroke 29:1248–1254

    PubMed  CAS  Google Scholar 

  31. Chandrasekaran K, Mehrabian Z, Spinnewyn B, Drieuand K, Fiskum G (2001) Neuroprotective effects of bilobalide, a component of the Ginkgo biloba extract (EGb 761), in gerbil global brain ischemia. Brain Res 922:282–292

    Article  PubMed  CAS  Google Scholar 

  32. Shen H, Zhang L, Yuen D, Logan R, Jung BP, Zhang G, Eubanks JH (2002) Expression and function of A1 adenosine receptors in the rat hippocampus following transient forebrain ischemia. Neuroscience 114:547–556

    Article  PubMed  CAS  Google Scholar 

  33. Fuh KC, Meneshian A, Patel CB, Takiar V, Bulkley GB (2002) Signal transduction by reactive oxygen species: alternative paradigms for signaling specificity. Surgery 131:601–612

    Article  PubMed  Google Scholar 

  34. Candelario-Jalil E, Alvarez D, Merino N, Sonia Leon O (2003) Delayed treatment with nimesulide reduces oxidative stress following global ischemic brain injury in gerbils. Neurosci Res 47:245–253

    Article  PubMed  CAS  Google Scholar 

  35. Al-Majed AA (2004) Aminoguanidine prevents oxidative stress insult following transient forebrain ischemia in the rat hippocampus. Saudi Pharmaceutic J 12:150–156

    CAS  Google Scholar 

  36. Kono Y, Fridovich I (1982) Superoxide radical inhibits catalase. J Biol Chem 25:5751–5754

    Google Scholar 

  37. Tokuda Y, Uozumi T, Kawassaki T (1993) The superoxide dismutase activities of cerebral tissues, assayed by the chemiluminescence method, in the gerbil focal ischemia/reperfusion and global ischemia models. Neurochem Int 23:107–114

    Article  PubMed  CAS  Google Scholar 

  38. Homi HM, Freitas JJ, Curi R, Velasco IT, Junior BA (2002) Changes in superoxide dismutase and catalase activities of rat brain regions during early global cerebral transient ischemia/reperfusion. Neurosci Lett 333:37–40

    Article  PubMed  CAS  Google Scholar 

  39. Ghoneim AI, Abdel-naim AB, Khalifa AE, El-denshary ES (2002) Protective effects of curcumin against ischemia/reperfusion insult in rat forebrain. Pharmacol Res 46:273–279

    Article  PubMed  CAS  Google Scholar 

  40. Thiyagarajan M, Sharma SS (2004) Neuroprotective effect of curcumin in middle cerebral artery occlusion induced focal cerebral ischemia in rats. Life Sci 74:969–985

    Article  PubMed  CAS  Google Scholar 

  41. Wang Q, Sun AY, Simonyi A, Jensen MD, Shelat PB, Rottinghaus GE, MacDonald RS, Miller DK, Lubahn DE, Weisman GA, Sun GY (2005) Neuroprotective mechanisms of curcumin against cerebral ischemia-induced neuronal apoptosis and behavioral deficits. J Neurosci Res 82:138–148

    Article  PubMed  CAS  Google Scholar 

  42. Naik RS, Mujumdar AM, Ghaskadbi S (2004) Protection of liver cells from ethanol cytotoxicity by curcumin in liver slice culture in vitro. J Eethanopharmacol 95:31–37

    Article  CAS  Google Scholar 

  43. Shoskes DA (1998) Effect of bioflavonoids quercetin and curcumin on ischemic renal injury: a new class of renoprotective agents. Transplantation 27:147–152

    Article  Google Scholar 

  44. Manikandan P, Sumitra M, Aishwarya S, Manohar BM, Lokanadam B, Puvanakrishnan R (2004) Curcumin modulates free radical quenching in myocardial ischaemia in rats. Int J Biochem Cell Biol 36:1967–1980

    Article  PubMed  CAS  Google Scholar 

  45. Sinet PM, Heikkila RE, Cohen G (1980) Hydrogen peroxide production by rat brain in vivo. J Neurochem 34:1421–1428

    Article  PubMed  CAS  Google Scholar 

  46. Paget GE, Barnes JM (eds) (1964) In evaluation of drug activities: pharmacometrics. Academic press, New York and London

  47. Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR, Ming-Shiang W, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ, Tsai CC, Hsieh CY (2001) Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 21:2895–2900

    PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by operating grant from King Abdulaziz City for Science & Technology (KACST; LP-8-49).

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Authors and Affiliations

  1. Department of Pharmacology, College of Pharmacy, King Saud University, P.O. Box 2457, 11451, Riyadh, Kingdom of Saudi Arabia

    Fadhel A. Al-Omar, Mahmoud N. Nagi, Mustafa M. Abdulgadir, Khalda S. Al Joni & Abdulhakeem A. Al-Majed

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  1. Fadhel A. Al-Omar
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  2. Mahmoud N. Nagi
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  3. Mustafa M. Abdulgadir
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Correspondence to Abdulhakeem A. Al-Majed.

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Al-Omar, F.A., Nagi, M.N., Abdulgadir, M.M. et al. Immediate and Delayed Treatments with Curcumin Prevents Forebrain Ischemia-Induced Neuronal Damage and Oxidative Insult in the Rat Hippocampus. Neurochem Res 31, 611–618 (2006). https://doi.org/10.1007/s11064-006-9059-1

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