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In vitro effects of iron chelation of curcumin Fe (III) complex

Year 2019, Volume: 44 Issue: 3, 947 - 951, 30.09.2019
https://doi.org/10.17826/cumj.484672

Abstract

urpose: The aim of this study was to investigate the cytotoxicity effect, iron chelator and antioxidant activities of iron (III) ions with curcumin ligand that may be used in the treatment of iron overload. 

Materials and Methods: The cytotoxic activities of the ligand and the complex were evaluated by the MTT assay. The SOD activity of the complex of curcumin was determined by using its ability to inhibit the reduction of NBT. The catalytic activity studies of Fe(III) complex in DMSO towards the disproportionation of hydrogen peroxide were also performed.

Results: The IC50 values are found in 6.8 μM catalase activity was measured. Where at a concentration of 2.0 mM, the activity was equivalent to 183.30 U/L. The complex shows a catalase activity. The complex showed minimal toxicity. IC50 values found 5.3 mg/ml. The observed cytotoxicity could be pursued to obtain a potential drug. The iron chelator effects were determined by Ferrozine reagent. Curcumin, the most active extract interfered with the formation of ferrous and ferrozine complex. It demonstrated strong chelating activities. The result showed that the complexes possess considerable SOD activity. This finding indicates that the iron complex is capable of removing free radicals.  

Conclusion:  The study results revealed that the iron(III) complex of curcumin with an appropriate potential drug may act as a protector against oxidative stress. Therefore, all results suggest that curcumin may represent a new approach in the treatment of iron overload.


References

  • REFERENCES
  • 1. Cairo G, F, Recalcati S. A precious metal: Iron, an essential nutrient for all cells. Genes & Nutrition, 2006, 1:25-39.
  • 2. Kim A, Nemeth E, New insights into iron regulation and erythropoiesis. Curr Opin Hematol. 2015 22(3): 199–205.
  • 3. Özbolat G, Yegani AA, Tuli A. Synthesis, characterization and electrochemistry studies of iron (iii) complex with curcumin ligand.2018; https://doi.org/10.1111/1440-1681.12964.
  • 4. Siah CW, Ombiga J, Adams LA, Trinder D, Olynyk JK. Normal Iron Metabolism and the Pathophysiology of Iron Overload Disorders. Clin Biochem Rev. 2006; 27(1): 5–16.
  • 5. Batt KP. Iron overload syndromes and the liver. Modern Pathology (2007) 20, S31–S39.
  • 6. Lindsey WT, Bernie PD, Pharm RD. Deferasirox for Transfusion-Related Iron Overload: A Clinical Review. Clinical Therapeutics,2007; 29(10):2154-2166.
  • 7. Özbolat G, Tuli A. Iron chelating ligand for iron overload diseases. Bratisl Med J. 2018; 119 (5) 308–311.
  • 8. Shander A, Cappellini MD, Goodnough L. Iron overload and toxicity: the hidden risk of multiple blood transfusions. Vox Sang; 2009; 97:185–97.
  • 9. Ehteram H, Bavarsad MS, Mokhtari M, et al. Prooxidant-antioxidant balance and hs-CRP in patients with beta-thalassemia major. Clin Lab. 2014; 60(2):207-15.
  • 10. Shander A, Cappellini MD, Goodnough L (2009) Iron overload and toxicity: the hidden risk of multiple blood transfusions. Vox Sang; 97:185–97.
  • 11. Tam T.F, Leung-Toung R, Li W, Wang Y, Karimian K, Spino M. Iron chelator research: past, present and future. Cur Med Chem, 2003; 10:983.
  • 12. Nisbet-Brown E, Olivieri NF, Giardina PJ, Grady RW, Neufeld EJ et al. Effectiveness and safety of ICL670 in iron-loaded patients with thalassaemia: a randomized, double-blind, placebocontrolled, dose-escalation trial. Lancet 2003;361:1597-602.
  • 13. Jordan LB, Vekeman F. Sengupta A, et al. Persistence and compliance of deferoxamine versus deferasirox in Medicaid patients with sickle-cell disease. J. Clin. Pharm. Ther.2012; 37: 173e181.
  • 14. Kalinowski DS, Richardson DR. The Evolution of Iron Chelators for the Treatment of Iron Overload Disease and Cancer. Pharmacol. Rev.2005; 57: 547e583.
  • 15. Zhang J, Hou X, Ahmad H, Zhang H, Zhang L, et al. Assessment of free radicals scavenging activity of seven natural pigments and protective effects in AAPH-challenged chicken erythrocytes.Food Chem, 2014, 145: 57–65.
  • 16. Crisponi G, Nurchi VM, Zoroddu M.A. Iron chelating agents for Iron overload diseases. Thalasemia Reports,2014; 4(2).
  • 17. Aggarwal BB. Sundaram C. Malani N, et al. Curcumin: the Indian solid gold. Advances in Experimental Medicine and Biology, 2007;595, 1-75.
  • 18. Mei X. Luo X. Xu S, et al. Gastroprotective effects of a new zinc(II)-curcumin complex against pylorus-ligature-induced gastric ulcer in rats. Chemico-Biological Interactions. 2009; 181:316–321.
  • 19. Jiao Y. Wilkinson J. Pietsch EC, et al. Iron chelation in the biological activity of curcumin. Free Radic. Bio. Med. 2006; 40: 1152–1160.
  • 20. Banerjee R. Inhibitory Effect of Curcumin-Cu(II) and Curcumin-Zn(II) Complexes on Amyloid-Beta Peptide Fibrillation. Bioinorg Chem Appl. 2014: 325873.
  • 21. Kocaadam B. Şanlier N. Curcumin, an active component of turmeric (Curcuma longa), and its effects on health. Crit Rev Food Sci Nutr. 2017, 2;57(13):2889-2895.
  • 22. Messne DJ, Sivam G, Kowdley KV. Curcumin reduces the toxic effects of iron loading in rat liver. Liver Int. 2009; 29(1): 63–72.
  • 23. Oberley LW. Spitz DR. Greenwald RA. Handbook for Methods for Oxygen Radicals Research, CRC Press. Boca Ratón, FL, 1986; 217.
  • 24. Khalil M.I., Al-Zahem A., Al-Qunaibi MH. Synthesis, Characterization, Mössbauer Parameters, and Antitumor Activity of Fe(III) Curcumin Complex. Corporation Bioinorganic Chemistry and Applications 2013, 982423.
  • 25. Zhoua T, Hider RC, Liu ZD, Neubert H. Iron(III)-selective dendritic chelators. ScienceDirect.2004; 45(51): 9393-9396.
  • 26. Aggarwal BB. Sundaram C. Malani N, et al. (2007) Advances in Experimental Medicine and Biology, 595, 1-75.
  • 27. Mei X. Luo X. Xu S, et al.(2009) Gastroprotective effects of a new zinc(II)- curcumin complex against pylorus-ligature-induced gastric ulcer in rats. Chemico- Biological Interactions. 181:316–321.
  • 28. Jiao Y. Wilkinson J. Pietsch EC, et al.(2006) Iron chelation in the biological activity of curcumin Free Radic. Bio. Med. 40: 1152–1160.
  • 29. Donald J. Messne. Gowsala Sivam. Kris V. Kowdley. (2009) Curcumin reduces the toxic effects of iron loading in rat liver. Liver Int. 29(1): 63–72.

Kurkumin demir(III) kompleksinin demir şelasyonunun in vitro etkileri

Year 2019, Volume: 44 Issue: 3, 947 - 951, 30.09.2019
https://doi.org/10.17826/cumj.484672

Abstract

Amaç: Bu çalışmanın amacı, aşırı demir yüklenmesinin tedavisinde kullanılması muhtemel olan kurkumin ligandı ve demir(III) iyonlarının sitotoksik etkisini, demir şelatörünü ve antioksidan etkinliğini araştırmaktır.

Gereç ve Yöntem: Ligandın ve kompleksin sitotoksik etkileri MTT yöntemi kullanılarak değerlendirildi. Kurkumin kompleksinin SOD etkinliği, kompleksin NBT azaltımını inhibe etme kabiliyetine göre belirlendi. Buna ilaveten, demir(III) kompleksinin DMSO’daki hidrojen peroksitin disproporsiyonu reaksiyonuna yönelik katalitik etkinliği de çalışıldı.

Bulgular: IC50 değerleri, 6.8 μM katalaz etkinliğinde ölçüldü. Konsantrasyonun 2.0 mM, olduğu durumda etkinlik seviyesi 183.30 U/L olarak ölçüldü. Kompleksin katalaz etkinliği gösterdiği ve minimal seviyede toksisiteye sebep olduğu görüldü. IC50 değerlerinin, 5.3 mg/ml’ye denk geldiği görüldü. Gözlenen sitotoksisitenin takip edilmesiyle, potansiyel bir ilacın elde edilmesinin muhtemel olduğu görüldü. Demir şelatörün etkileri Ferrozin reaktif bileşiği ile belirlendi. Demir ve Ferrozine kompleksinin oluşmasına müdahale eden en aktif ekstraktın kurkumin olduğu görüldü. Ayrıca, kurkuminin güçlü şelasyon etkinliğine sahip olduğu görüldü. Elde edilen bulgular bu komplekslerin önemli derecede SOD etkinliğine sahip oldukları görüldü. Dolaysıyla bu bulgular demir kompleksinin serbest radikalleri yok etme gücüne sahip olduğuna işaret etmektedirler.

Sonuç: Bu çalışmada elde edilen bulgular, uygun bir potansiyel ilaç ile beraber kullanıldığında demir(III) kurkumin kompleksinin oksidatif strese karşı bir koruyucu olarak işlev görebileceğini göstermektedir. Dolayısıyla elde edilen bütün bulgular, kurkuminin aşırı demir yüklenmesinin tedavisinde yeni bir yaklaşım olabileceğine işaret etmektedirler.


References

  • REFERENCES
  • 1. Cairo G, F, Recalcati S. A precious metal: Iron, an essential nutrient for all cells. Genes & Nutrition, 2006, 1:25-39.
  • 2. Kim A, Nemeth E, New insights into iron regulation and erythropoiesis. Curr Opin Hematol. 2015 22(3): 199–205.
  • 3. Özbolat G, Yegani AA, Tuli A. Synthesis, characterization and electrochemistry studies of iron (iii) complex with curcumin ligand.2018; https://doi.org/10.1111/1440-1681.12964.
  • 4. Siah CW, Ombiga J, Adams LA, Trinder D, Olynyk JK. Normal Iron Metabolism and the Pathophysiology of Iron Overload Disorders. Clin Biochem Rev. 2006; 27(1): 5–16.
  • 5. Batt KP. Iron overload syndromes and the liver. Modern Pathology (2007) 20, S31–S39.
  • 6. Lindsey WT, Bernie PD, Pharm RD. Deferasirox for Transfusion-Related Iron Overload: A Clinical Review. Clinical Therapeutics,2007; 29(10):2154-2166.
  • 7. Özbolat G, Tuli A. Iron chelating ligand for iron overload diseases. Bratisl Med J. 2018; 119 (5) 308–311.
  • 8. Shander A, Cappellini MD, Goodnough L. Iron overload and toxicity: the hidden risk of multiple blood transfusions. Vox Sang; 2009; 97:185–97.
  • 9. Ehteram H, Bavarsad MS, Mokhtari M, et al. Prooxidant-antioxidant balance and hs-CRP in patients with beta-thalassemia major. Clin Lab. 2014; 60(2):207-15.
  • 10. Shander A, Cappellini MD, Goodnough L (2009) Iron overload and toxicity: the hidden risk of multiple blood transfusions. Vox Sang; 97:185–97.
  • 11. Tam T.F, Leung-Toung R, Li W, Wang Y, Karimian K, Spino M. Iron chelator research: past, present and future. Cur Med Chem, 2003; 10:983.
  • 12. Nisbet-Brown E, Olivieri NF, Giardina PJ, Grady RW, Neufeld EJ et al. Effectiveness and safety of ICL670 in iron-loaded patients with thalassaemia: a randomized, double-blind, placebocontrolled, dose-escalation trial. Lancet 2003;361:1597-602.
  • 13. Jordan LB, Vekeman F. Sengupta A, et al. Persistence and compliance of deferoxamine versus deferasirox in Medicaid patients with sickle-cell disease. J. Clin. Pharm. Ther.2012; 37: 173e181.
  • 14. Kalinowski DS, Richardson DR. The Evolution of Iron Chelators for the Treatment of Iron Overload Disease and Cancer. Pharmacol. Rev.2005; 57: 547e583.
  • 15. Zhang J, Hou X, Ahmad H, Zhang H, Zhang L, et al. Assessment of free radicals scavenging activity of seven natural pigments and protective effects in AAPH-challenged chicken erythrocytes.Food Chem, 2014, 145: 57–65.
  • 16. Crisponi G, Nurchi VM, Zoroddu M.A. Iron chelating agents for Iron overload diseases. Thalasemia Reports,2014; 4(2).
  • 17. Aggarwal BB. Sundaram C. Malani N, et al. Curcumin: the Indian solid gold. Advances in Experimental Medicine and Biology, 2007;595, 1-75.
  • 18. Mei X. Luo X. Xu S, et al. Gastroprotective effects of a new zinc(II)-curcumin complex against pylorus-ligature-induced gastric ulcer in rats. Chemico-Biological Interactions. 2009; 181:316–321.
  • 19. Jiao Y. Wilkinson J. Pietsch EC, et al. Iron chelation in the biological activity of curcumin. Free Radic. Bio. Med. 2006; 40: 1152–1160.
  • 20. Banerjee R. Inhibitory Effect of Curcumin-Cu(II) and Curcumin-Zn(II) Complexes on Amyloid-Beta Peptide Fibrillation. Bioinorg Chem Appl. 2014: 325873.
  • 21. Kocaadam B. Şanlier N. Curcumin, an active component of turmeric (Curcuma longa), and its effects on health. Crit Rev Food Sci Nutr. 2017, 2;57(13):2889-2895.
  • 22. Messne DJ, Sivam G, Kowdley KV. Curcumin reduces the toxic effects of iron loading in rat liver. Liver Int. 2009; 29(1): 63–72.
  • 23. Oberley LW. Spitz DR. Greenwald RA. Handbook for Methods for Oxygen Radicals Research, CRC Press. Boca Ratón, FL, 1986; 217.
  • 24. Khalil M.I., Al-Zahem A., Al-Qunaibi MH. Synthesis, Characterization, Mössbauer Parameters, and Antitumor Activity of Fe(III) Curcumin Complex. Corporation Bioinorganic Chemistry and Applications 2013, 982423.
  • 25. Zhoua T, Hider RC, Liu ZD, Neubert H. Iron(III)-selective dendritic chelators. ScienceDirect.2004; 45(51): 9393-9396.
  • 26. Aggarwal BB. Sundaram C. Malani N, et al. (2007) Advances in Experimental Medicine and Biology, 595, 1-75.
  • 27. Mei X. Luo X. Xu S, et al.(2009) Gastroprotective effects of a new zinc(II)- curcumin complex against pylorus-ligature-induced gastric ulcer in rats. Chemico- Biological Interactions. 181:316–321.
  • 28. Jiao Y. Wilkinson J. Pietsch EC, et al.(2006) Iron chelation in the biological activity of curcumin Free Radic. Bio. Med. 40: 1152–1160.
  • 29. Donald J. Messne. Gowsala Sivam. Kris V. Kowdley. (2009) Curcumin reduces the toxic effects of iron loading in rat liver. Liver Int. 29(1): 63–72.
There are 30 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Research
Authors

Gülüzar Özbolat 0000-0002-3487-1088

Arash Alizadeh Yegani This is me 0000-0003-0334-8152

Publication Date September 30, 2019
Acceptance Date February 8, 2019
Published in Issue Year 2019 Volume: 44 Issue: 3

Cite

MLA Özbolat, Gülüzar and Arash Alizadeh Yegani. “In Vitro Effects of Iron Chelation of Curcumin Fe (III) Complex”. Cukurova Medical Journal, vol. 44, no. 3, 2019, pp. 947-51, doi:10.17826/cumj.484672.