Skip to main content
Neuroscience Bulletin logoLink to Neuroscience Bulletin
. 2012 Jul 11;28(3):253–258. doi: 10.1007/s12264-012-1238-2

Curcumin protects nigral dopaminergic neurons by iron-chelation in the 6-hydroxydopamine rat model of Parkinson’s disease

Xi-Xun Du 1, Hua-Min Xu 1, Hong Jiang 1, Ning Song 1, Jun Wang 1, Jun-Xia Xie 1,
PMCID: PMC5560326  PMID: 22622825

Abstract

Objective

Curcumin is a plant polyphenolic compound and a major component of spice turmeric (Curcuma longa). It has been reported to possess free radical-scavenging, iron-chelating, and anti-inflammatory properties in different tissues. Our previous study showed that curcumin protects MES23.5 dopaminergic cells from 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in vitro. The present study aimed to explore this neuroprotective effect in the 6-OHDAlesioned rat model of Parkinson’s disease in vivo.

Methods

Rats were given intragastric curcumin for 24 days. 6-OHDA lesioning was conducted on day 4 of curcumin treatment. Dopamine content was assessed by high-performance liquid chromatography with electrochemical detection, tyrosine hydroxylase (TH)-containing neurons by immunohistochemistry, and iron-containing cells by Perls’ iron staining.

Results

The dopamine content in the striatum and the number of TH-immunoreactive neurons decreased after 6-OHDA treatment. Curcumin pretreatment reversed these changes. Further studies demonstrated that 6-OHDA treatment increased the number of iron-staining cells, which was dramatically decreased by curcumin pretreatment.

Conclusion

The protective effects of curcumin against 6-OHDA may be attributable to the ironchelating activity of curcumin to suppress the iron-induced degeneration of nigral dopaminergic neurons.

Keywords: 6-hydroxydopamine, curcumin, Parkinson’s disease, dopaminergic neurons, iron

References

  • [1].Youdim M.B., Ben-Shachar D., Riederer P. The role of monoamine oxidase, iron-melanin interaction, and intracellular calcium in Parkinson’s disease. J Neural Transm Suppl. 1990;32:239–248. doi: 10.1007/978-3-7091-9113-2_34. [DOI] [PubMed] [Google Scholar]
  • [2].Jiang H., Song N., Wang J., Ren L.Y., Xie J.X. Peripheral iron dextran induced degeneration of dopaminergic neurons in rat substantia nigra. Neurochem Int. 2007;51:32–36. doi: 10.1016/j.neuint.2007.03.006. [DOI] [PubMed] [Google Scholar]
  • [3].Ke Y., Ming Qian Z. Iron misregulation in the brain: a primary cause of neurodegenerative disorders. Lancet Neurol. 2003;2:246–253. doi: 10.1016/S1474-4422(03)00353-3. [DOI] [PubMed] [Google Scholar]
  • [4].Youdim M.B., Stephenson G., Ben Shachar D. Ironing iron out in Parkinson’s disease and other neurodegenerative diseases with iron chelators: a lesson from 6-hydroxydopamine and iron chelators, desferal and VK-28. Ann N Y Acad Sci. 2004;1012:306–325. doi: 10.1196/annals.1306.025. [DOI] [PubMed] [Google Scholar]
  • [5].Onyango I.G. Mitochondrial dysfunction and oxidative stress in Parkinson’s disease. Neurochem Res. 2008;33:589–597.. doi: 10.1007/s11064-007-9482-y. [DOI] [PubMed] [Google Scholar]
  • [6].Sarafanov A.G., Todorov T.I., Kajdacsy-Balla A., Gray M.A., Macias V., Centeno J.A. Analysis of iron, zinc, selenium and cadmium in paraffin-embedded prostate tissue specimens using inductively coupled plasma mass-spectrometry. J Trace Elem Med Biol. 2008;22:305–314. doi: 10.1016/j.jtemb.2008.03.010. [DOI] [PubMed] [Google Scholar]
  • [7].Meissner W., Hill M.P., Tison F., Gross C.E., Bezard E. Neuroprotective strategies for Parkinson’s disease: conceptual limits of animal models and clinical trials. Trends Pharmacol Sci. 2004;25:249–253. doi: 10.1016/j.tips.2004.03.003. [DOI] [PubMed] [Google Scholar]
  • [8].Slikkker W., Youdim M., Palmer G.C., Hall E., Williams C., Trembly B. The future of neuroprotection. Ann N Y Acad Sci. 1999;890:529–533. doi: 10.1111/j.1749-6632.1999.tb08035.x. [DOI] [PubMed] [Google Scholar]
  • [9].Hanasaki Y., Ogawa S., Fukui S. The correlation between active oxygens scavenging and antioxidative effects of flavonoids. Free Radic Biol Med. 1994;16:845–850. doi: 10.1016/0891-5849(94)90202-X. [DOI] [PubMed] [Google Scholar]
  • [10].Morel I., Lescoat G., Cogrel P., Sergent O., Pasdeloup N., Brissot P., et al. Antioxidant and iron-chelating activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures. Biochem Pharmacol. 1993;45:13–19. doi: 10.1016/0006-2952(93)90371-3. [DOI] [PubMed] [Google Scholar]
  • [11].Santel T., Pflug G., Hemdan N.Y., Schafer A., Hollenbach M., Buchold M., et al. Curcumin inhibits glyoxalase 1: a possible link to its antiinflammatory and anti-tumor activity. PLoS One. 2008;3:e3508. doi: 10.1371/journal.pone.0003508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [12].Masuda T., Hidaka K., Shinohara A., Maekawa T., Takeda Y., Yamaguchi H. Chemical studies on antioxidant mechanism of curcuminoid: analysis of radical reaction products from curcumin. J Agric Food Chem. 1999;47:71–77. doi: 10.1021/jf9805348. [DOI] [PubMed] [Google Scholar]
  • [13].Daniel S., Limson J.L., Dairam A., Watkins G.M., Daya S. Through metal binding, curcumin protects against lead- and cadmiuminduced lipid peroxidation in rat brain homogenates and against lead-induced tissue damage in rat brain. J Inorg Biochem. 2004;98:266–275. doi: 10.1016/j.jinorgbio.2003.10.014. [DOI] [PubMed] [Google Scholar]
  • [14].Chen J., Tang X.Q., Zhi J.L., Cui Y., Yu H.M., Tang E.H., et al. Curcumin protects PC12 cells against 1-methyl-4-phenylpyridinium ioninduced apoptosis by bcl-2-mitochondria-ROS-iNOS pathway. Apoptosis. 2006;11:943–953. doi: 10.1007/s10495-006-6715-5. [DOI] [PubMed] [Google Scholar]
  • [15].Wang J., Du X.X., Jiang H., Xie J.X. Curcumin attenuates 6-hydroxydopamine-induced cytotoxicity by anti-oxidation and nuclear factor-kappa B modulation in MES23.5 cells. Biochem Pharmacol. 2009;78:178–183. doi: 10.1016/j.bcp.2009.03.031. [DOI] [PubMed] [Google Scholar]
  • [16].Jiang H., Song N., Xu H., Zhang S., Wang J., Xie J. Up-regulation of divalent metal transporter 1 in 6-hydroxydopamine intoxication is IRE/IRP dependent. Cell Res. 2010;20:345–356. doi: 10.1038/cr.2010.20. [DOI] [PubMed] [Google Scholar]
  • [17].Ma Z.G., Wang J., Jiang H., Liu T.W., Xie J.X. Myricetin reduces 6-hydroxydopamine-induced dopamine neuron degeneration in rats. Neuroreport. 2007;18:1181–1185. doi: 10.1097/WNR.0b013e32821c51fe. [DOI] [PubMed] [Google Scholar]
  • [18].Dexter D.T., Statton S.A., Whitmore C., Freinbichler W., Weinberger P., Tipton K.F., et al. Clinically available iron chelators induce neuroprotection in the 6-OHDA model of Parkinson’s disease after peripheral administration. J Neural Transm. 2011;118:223–231. doi: 10.1007/s00702-010-0531-3. [DOI] [PubMed] [Google Scholar]
  • [19].Ak T., Gulcin I. Antioxidant and radical scavenging properties of curcumin. Chem Biol Interact. 2008;174:27–37. doi: 10.1016/j.cbi.2008.05.003. [DOI] [PubMed] [Google Scholar]
  • [20].Messner D.J., Sivam G., Kowdley K.V. Curcumin reduces the toxic effects of iron loading in rat liver epithelial cells. Liver Int. 2009;29:63–72. doi: 10.1111/j.1478-3231.2008.01793.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [21].Earl C.D., Reum T., Xie J.X., Sautter J., Kupsch A., Oertel W.H., et al. Foetal nigral cell suspension grafts influence dopamine release in the non-grafted side in the 6-hydroxydopamine rat model of Parkinson’s disease: in vivo voltammetric data. Exp Brain Res. 1996;109:179–184. doi: 10.1007/BF00228642. [DOI] [PubMed] [Google Scholar]
  • [22].Wang J., Xu H.M., Yang H.D., Du X.X., Jiang H., Xie J.X. Rg1 reduces nigral iron levels of MPTP-treated C57BL6 mice by regulating certain iron transport proteins. Neurochem Int. 2009;54:43–48. doi: 10.1016/j.neuint.2008.10.003. [DOI] [PubMed] [Google Scholar]
  • [23].Blum D., Torch S., Lambeng N., Nissou M., Benabid A.L., Sadoul R., et al. Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson’s disease. Prog Neurobiol. 2001;65:135–172. doi: 10.1016/S0301-0082(01)00003-X. [DOI] [PubMed] [Google Scholar]
  • [24].Salazar J., Mena N., Hunot S., Prigent A., Alvarez-Fischer D., Arredondo M., et al. Divalent metal transporter 1 (DMT1) contributes to neurodegeneration in animal models of Parkinson’s disease. Proc Natl Acad Sci U S A. 2008;105:18578–18583. doi: 10.1073/pnas.0804373105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [25].Jiang H., Luan Z., Wang J., Xie J. Neuroprotective effects of iron chelator Desferal on dopaminergic neurons in the substantia nigra of rats with iron-overload. Neurochem Int. 2006;49:605–609. doi: 10.1016/j.neuint.2006.04.015. [DOI] [PubMed] [Google Scholar]

Articles from Neuroscience Bulletin are provided here courtesy of Springer

RESOURCES