Skip to main content

Advertisement

Log in

Alleviation Effect of Grape Seed Proanthocyanidins on Neuronal Apoptosis in Rats with Iron Overload

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

We aimed to evaluate the effect of grape seed proanthocyanidins (GSPCs) on neuronal apoptosis, particularly through their roles in maintaining divalent mineral element balance and resisting oxidation in rats with iron overload. A total of 40 Sprague–Dawley rats were randomly divided into control, iron overload, GSPCs, and iron overload + GSPCs groups. The iron, calcium, zinc, magnesium, and copper contents in the brain tissue of the rats were measured using inductively coupled plasma mass spectrometry. Their oxidative stress state was determined using the relevant kit. The number of apoptotic neurons was evaluated using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and synaptosome numbers were determined using the immunohistochemical approach. Fas, Bax, and Bcl-2 gene expressions in the cortex and hippocampus were detected using quantitative real-time polymerase chain reaction. After 7 weeks, compared with the control group, the zinc and magnesium contents; superoxide dismutase, glutathione peroxidase, and catalase activities; and synaptophysin and Bcl-2 gene expressions in the iron overload group were significantly decreased, whereas the iron, calcium contents, and malondialdehyde contents; TUNEL-positive cell numbers; and Fas and Bax gene expressions were significantly increased. There were no significant changes in the copper content. Conversely, the rats exhibited better recovery when GSPCs were used instead of iron alone. In summary, GSPCs protected against iron overload induced neuronal apoptosis in rats by maintaining the divalent mineral element balance, reducing oxidative stress, and regulating apoptotic genes expressions.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Zhao GH (2010) Phytoferritin and its implications for human health and nutrition. Biochim Biophys Acta 1800:815–823

    Article  CAS  Google Scholar 

  2. Pinero D, Jones B, Beard J (2001) Variations in dietary iron alter behavior in developing rats. J Nutr 131:311–318

    Article  CAS  Google Scholar 

  3. Sobotka TJ, Whittaker P, Sobotka JM, Brodie RE, Quander DY, Robl M, Bryant M, Barton CN (1996) Neurobehavioral dysfunctions associated with dietary iron overload. Physiol Behav 59:213–219

    Article  CAS  Google Scholar 

  4. Fredriksson A, Schroder N, Eriksson P, Izquierdo I, Archer T (1999) Neonatal iron exposure induces neurobehavioural dysfunctions in adult mice. Toxicol Appl Pharmacol 159:25–30

    Article  CAS  Google Scholar 

  5. Maaroufi K, Ammari M, Jeljeli M, Roy V, Sakly M, Abdelmelek H (2009) Impairment of emotional behavior and spatial learning in adult Wistar rats by ferrous sulfate. Physiol Behav 96:343–349

    Article  CAS  Google Scholar 

  6. de Lima MNM, Polydoro M, Laranja DC, Bonatto F, Bromberg E, Moreira JCF, Dal-Pizzol F, Schröder N (2005) Recognition memory impairment and brain oxidative stress induced by postnatal iron administration. Eur J Neurosci 21:2521–2528

    Article  Google Scholar 

  7. da Silva VK, de Freitas BS, da Silva Dornelles A, Nery LR, Falavigna L, Ferreira RD, Bogo MR, Hallak JEC, Zuardi AW, Crippa JAS, Schröder N (2014) Cannabidiol normalizes caspase 3, synaptophysin, and mitochondrial fission protein dnm1l expression levels in rats with brain iron overload: implications for neuroprotection. Mol Neurobiol 49:222–233

    Article  Google Scholar 

  8. Lee DG, Kam MK, Kim KM, Kim HS, Kwon OS, Lee HS, Lee DS (2018) Peroxiredoxin 5 prevents iron overload-induced neuronal death by inhibiting mitochondrial fragmentation and endoplasmic reticulum stress in mouse hippocampal HT-22 cells. Int J Biochem Cell Biol 102:10–19

    Article  CAS  Google Scholar 

  9. Tirgar PR, Desai TR (2011) Investigation into iron chelating activity of Triticum aestivum (wheat grass) in iron­dextran induce iron overload model of thalassaemia. J Pharm Res 4:3066–3069

    Google Scholar 

  10. Patel R, Tirgar P (2013) Evaluation of beneficial effects of Medicago sativa (alfalfa) in iron-overload conditions. J Chem Bio Phy Sci Sec B 3:2628–2643

    Google Scholar 

  11. Mobarra N, Shanaki M, Ehteram H, Nasiri H, Sahmani M, Saeidi M, Goudarzi M, Pourkarim H, Azad M (2016) A review on iron chelators in treatment of iron overload syndromes. Int J Hematol Oncol Stem Cell Res 10:239–247

    PubMed  PubMed Central  Google Scholar 

  12. Yosia M, Wahidiyat PA (2017) Side effect of deferiprone as iron chelator in children with thalassemia. Paediatr Indones 57:329–336

    Article  Google Scholar 

  13. Grady RW, Galanello R, Randolph RE, Kleinert DA, Dessi C, Giardina PJ (2013) Toward optimizing the use of deferasirox: potential benefits of combined use with deferoxamine. Haematologica 98:129–135

    Article  CAS  Google Scholar 

  14. Nassiri-Asl M, Hosseinzadeh H (2016) Review of the pharmacological effects of Vitis vinifera (grape) and its bioactive constituents: an update. Phytother Res 30:1392–1403

    Article  CAS  Google Scholar 

  15. de la lglesia R, Milagro FI, Campion J, Boque N, Martinez JA (2010) Healthy properties of proanthocyanidins. Biofactors 36:159–168

    Article  Google Scholar 

  16. EI-Sayed EM, Mansour AM, EI-Sawy WS (2017) Protective effect of proanthocyanidins against doxorubicin-induced nephrotoxicity in rats. J Biochem Mol Toxicol 31:e21965

    Article  Google Scholar 

  17. Perron NR, Brumaghim JL (2009) A review of the antioxidant mechanisms of polyphenol compounds related to iron binding. Cell Biochem Biophys 53:75–100

    Article  CAS  Google Scholar 

  18. Yun SJ, Zhang T, Li ML, Chen B, Zhao GH (2011) Proanthocyanidins inhibit iron absorption from soybean (Glycine max) seed ferritin in rats with iron deficiency anemia. Plant Food Hum Nutr 66:212–217

    Article  CAS  Google Scholar 

  19. He Q, Yang SY, Wang W, Wu ZJ, Ma HL, Lu Y (2016) Proanthocyanidins affects the neurotoxicity of abeta 25-35 on C57/bl6 mice. Eur Rev Med Pharmacol Sci 20:679–684

    CAS  PubMed  Google Scholar 

  20. Zhen JL, Qu ZZ, Fang HB, Fu L, Wu YP, Wang HC, Zang HM, Wang WP (2014) Effects of grape seed proanthocyanidin extract on pentylenetetrazole-induced kindling and associated cognitive impairment in rats. Int J Mol Med 34:391–398

    Article  CAS  Google Scholar 

  21. Strathearn KE, Yousef GG, Grace MH, Roy SL, Tambe MA, Ferruzzi MG, Wu QL, Simon JE, Lila MA, Rochet JC (2014) Neuroprotective effects of anthocyanin- and proanthocyanidin-rich extracts in cellular models of Parkinsons disease. Brain Res 1555:60–77

    Article  CAS  Google Scholar 

  22. Deng JJ, Li ML, Zhang T, Chen B, Leng XJ, Zhao GH (2011) Binding of proanthocyanidins to soybean (Glycine max) seed ferritin inhibiting protein degradation by protease in vitro. Food Res Int 44:33–38

    Article  CAS  Google Scholar 

  23. Draper HH, Hadley M (1990) Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 86:421–431

    Article  Google Scholar 

  24. Sun Y, Oberley LW, Li Y (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34:497–500

    Article  CAS  Google Scholar 

  25. Soslow RA, Dannenberg AJ, Rush D, Woerner BM, Nasir Khan K, Masferrer J, Koki AT (2000) COX-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer 89:2637–2645

    Article  CAS  Google Scholar 

  26. Ma ZG, Zhou Y, Xie JX (2012) Nifedipine prevents iron accumulation and reverses iron overload induced dopamine neuron degeneration in the substantia nigra of rats. Nurotox Res 22:274–279

    Article  CAS  Google Scholar 

  27. Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger S, Gollan JL, Hediger MA (1997) Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388:482–488

    Article  CAS  Google Scholar 

  28. Qureshi GA, Memon SA, Memon AB, Ghouri RA, Memon JM, Parvez SH (2005) The emerging role of iron, zinc, copper, magnesium and selenium and oxidative stress in health and diseases. Biogenic Amines 19:147–169

    Article  CAS  Google Scholar 

  29. Schuchardt JP, Hahn A (2017) Intestinal absorption and factors influencing bioavailability of magnesium-an update. Curr Nutr Food Sci 13:260–278

    Article  CAS  Google Scholar 

  30. Reznichenko L, Amit T, Zheng H, Avramovich-Tirosh Y, Youdim MBH, Weinreb O, Mandel S (2006) Reduction of iron regulated amyloid precursor protein and β-amyloid peptide by (−)-epigallocatechin-3-gallate in cell cultures: implications for iron chelation in Alzheimer’s disease. J Neurochem 97:527–536

    Article  CAS  Google Scholar 

  31. Record IR, McInerney JK, Dreosti IE (1996) Black tea, green tea, and tea polyphenols. Effects on trace element status in weanling rats. Biol Trace Elem Res 53:27–43

    Article  CAS  Google Scholar 

  32. Fleming RE, Migas MC, Zhou XY, Jiang J, Britton RS, Brunt EM, Tomatsu S, Waheed A, Bacon BR, Sly WS (1999) Mechanism of increased iron absorption in murine model of hereditary hemochromatosis: increased duodenal expression of the iron transporter DMT1. Proc Natl Acad Sci U S A 96:3143–3148

    Article  CAS  Google Scholar 

  33. Topf JM, Murray PT (2003) Hypomagnesemia and hypermagnesemia. Rev Endocr Metab Disord 4:195–206

    Article  Google Scholar 

  34. Moreira ELG, Rial D, Aguiar AS Jr, Figueiredo CP, Siqueira JM, DalBó S, Horst H, de Oliveira J, Mancini G, dos Santos TS, Villarinho JG, Pinheiro FV, Marino-Neto J, Ferreira J, De Bem AF, Latini A, Pizzolatti MG, Ribeiro-do-Valle RM, Prediger RDS (2010) Proanthocyanidin-rich fraction from Croton celtidifolius Baill confers neuroprotection in the intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine rat model of Parkinson’s disease. J Neural Transm 117:1337–1351

    Article  CAS  Google Scholar 

  35. Mesquita SD, Ferreira AC, Sousa JC, Santos NC, Correia-Neves M, Sousa N, Palha JA, Marques F (2012) Modulation of iron metabolism in aging and in Alzheimer’s disease: relevance of the choroid plexus. Front Cell Neurosci 6:1–10

    Article  Google Scholar 

  36. Formigari A, Irato P, Santon A (2007) Zinc, antioxidant systems and metallothionein in metal mediated-apoptosis: biochemical and cytochemical aspects. Comp Biochem Physiol C 146:443–459

    Google Scholar 

  37. Wanatabe-Fukunaga R, Brannan CI, Itoh N, Yonehara S, Copeland NG, Jenkins NA, Nagata S (1992) The cDNA structure, expression and chromosomal assignment of the Fas antigen. J Immunol 148:1274–1279

    Google Scholar 

  38. Hunter JJ, Parlow TG (1996) A peptide sequence from bax that converts bcl-2 into an activator of apoptosis. J Biol Chem 271:8521–8524

    Article  CAS  Google Scholar 

  39. Wilson C, Muñoz-Palma E, González-Billault C (2018) From birth to death: a role for reactive oxygen species in neuronal development. Semin Cell Dev Biol 80:43–49

    Article  CAS  Google Scholar 

Download references

Funding

This project was supported by the National Natural Science Foundation of China (31801551), Research Startup Funds from Shanxi Agricultural University (2013YJ30), and the Science and Technology Innovation Project of Higher Education in Shanxi Province (2016150).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Cuiping Feng.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All applicable international, national, and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the Shanxi Agricultural University at which the studies were conducted.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yun, S., He, X., Zhang, W. et al. Alleviation Effect of Grape Seed Proanthocyanidins on Neuronal Apoptosis in Rats with Iron Overload. Biol Trace Elem Res 194, 210–220 (2020). https://doi.org/10.1007/s12011-019-01766-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-019-01766-8

Keywords

Navigation