Research Article
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Effect of Bezafibrate on Deoxyribonucleic Acid in the Presence of Iron and Copper

Year 2019, Volume: 3 Issue: 3, 131 - 136, 31.12.2019

Abstract

Aim: Bezafibrate is generally used to treat hyperlipidemia and diabetic patients. Analysis of the effect of chemicals and drugs on DNA in the presence of iron and copper is a very important issue in medical research. Therefore this research aimed to analyze the effect of bezafibrate on DNA in the presence of iron and copper.  

Material and Methods: Supercoiled pUC19 plasmid DNA was treated with different concentrations of bezafibrate (2.6, 1.3, 0.13, 0.013 and 0.0013 mM) in the presence of copper, iron and copper plus hydrogen peroxide followed by analyzing in agarose gel (1%) electrophoresis.    

Results: Any of the bezafibrate concentrations did not break DNA in the presence of   FeSO4 and CuCl2. There was no difference in the density and sharpness of the bond of supercoiled DNA in the treated samples compared to the related bond in the control samples. Although 0.13, 0.013 and 0.0013 mM of bezafibrate could not protect the DNA against the hydrogen radicals, 2.6, 1.3 mM of the drug could protect DNA by concentration dependent manner. 

Conclusion: Our study shows that the harmful effect of bezafibrate on DNA fragmentation may be indirect.

Supporting Institution

Zonguldak Bülent Ecevit Üniversity

Project Number

2018-50737594-01

Thanks

We wish to thank the Zonguldak Bulent Ecevit University Scientific Research Commission for supporting our study

References

  • 1. Robins SJ. PPARα ligands and clinical trials: cardiovascular risk reduction with fibrates. J. Cardiovasc. Risk. 2001;8(4):195-201.
  • 2. Grygiel-Górniak B. Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications-a review. Nutr J. 2014;13(1):17-25.
  • 3. Franko A, Huypens P, Neschen S, et al. Bezafibrate improves insulin sensitivity and metabolic flexibility in STZ-induced diabetic mice. Diabetes. 2016;65(9):2540-2552.
  • 4. Erem C. Prevalence of overweight and obesity in Turkey. IJC Metab Endocr . 2015;8:38-41.
  • 5. Siramshetty VB, Nickel J, Omieczynski C, et al. Withdrawn—a resource for withdrawn and discontinued drugs. Nucleic Acids Res. 2015;44(D1):D1080-D1086.
  • 6. Rocco L, Peluso C, Cesaroni F, et al. Genomic damage in human sperm cells exposed in vitro to environmental pollutants. J. Environment Analytic Toxicol. 2012;2(117):10.4172.
  • 7. Tawfeeq MM, Suzuki T, Shimamoto K, et al. Evaluation of in vivo genotoxic potential of fenofibrate in rats subjected to two-week repeated oral administration. Arch. Toxicol. 2011;85(8):1003-1011.
  • 8. Davis JD, Lin S-Y. DNA damage and breast cancer. World J Clin Oncol. 2011;2(9):329.
  • 9. Sharpe C, Collet J, Belzile E, et al. The effects of tricyclic antidepressants on breast cancer risk. Br. J. Cancer. 2002;86(1):92.
  • 10. Bertoncini C, Meneghini R, Galembeck F, et al. Preferential Localization of Iron in The Chromatin of Fe-Enriched Cells Is Linked to DNA Cleavage Sites and Control of Carcinogenesis. J. Cancer Sci. Ther. 2016;8:213-215.
  • 11. Brewer GJ. Risks of copper and iron toxicity during aging in humans. Chem. Res. Toxicol. 2009;23(2):319-326.
  • 12. Alexander DD, Weed DL, Cushing CA, et al. Meta-analysis of prospective studies of red meat consumption and colorectal cancer. Eur. J. Cancer Prev. 2011;20(4):293-307.
  • 13. Guo J, Wei W, Zhan L. Red and processed meat intake and risk of breast cancer: a meta-analysis of prospective studies. Breast Cancer Res. Treat. 2015;151(1):191-198.
  • 14. Zhu H-C, Yang X, Xu L-P, et al. Meat consumption is associated with esophageal cancer risk in a meat-and cancer-histological-type dependent manner. Dig. Dis. Sci. 2014;59(3):664-673.
  • 15. Xue X-J, Gao Q, Qiao J-H, et al. Red and processed meat consumption and the risk of lung cancer: a dose-response meta-analysis of 33 published studies. Int. J. Clin. Exp. Med. 2014;7(6):1542.
  • 16. Zhang X, Yang Q. Association between serum copper levels and lung cancer risk: A meta-analysis. J. Int. Med. Res. 2018;46(12):4863-4873.
  • 17. Zhang M, Shi M, Zhao Y. Association between serum copper levels and cervical cancer risk: A meta-analysis. Biosci. Rep. 2018;38(4):BSR20180161.
  • 18. Yi Z-C, Liu Y-Z, Li H-X, et al. Chebulinic acid and tellimagrandin I inhibit DNA strand breaks by hydroquinone/Cu (II) and H2O2/Cu (II), but potentiate DNA strand breaks by H2O2/Fe (II). Toxicol In Vitro. 2009;23(4):667-673.
  • 19. Coban B, Yildiz U. DNA-binding studies and antitumor evaluation of novel water soluble organic pip and hpip analogs. Appl. Biochem. Biotechnol. 2014;172(1):248-262.
  • 20. Li Y, Zheng Y, Zhang Y, et al. Antioxidant Activity of Coconut (Cocos nucifera L.) Protein Fractions. Molecules. 2018;23(3):1-11.
  • 21. Valipour R, Yilmaz MB, Valipour E. Study of DNA-Binding Activity and Antibacterial Effect of Escitalopram Oxalate, an Extensively Prescribed Antidepressant. Drug Res (Stuttg). 2019.
  • 22. De Mattos J, Dantas F, Caldeira‐de‐Araújo A, et al. Agarose gel electrophoresis system in the classroom: detection of DNA strand breaks through the alteration of plasmid topology. Biochem. Mol. Biol. Educ. 2004;32(4):254-257.
  • 23. Moreno RG, Alipázaga MV, Gomes OF, et al. DNA damage and 2′-deoxyguanosine oxidation induced by S (IV) autoxidation catalyzed by copper (II) tetraglycine complexes: synergistic effect of a second metal ion. J. Inorg. Biochem. 2007;101(5):866-875.
  • 24. Letelier ME, Sánchez-Jofré S, Peredo-Silva L, et al. Mechanisms underlying iron and copper ions toxicity in biological systems: Pro-oxidant activity and protein-binding effects. Chem. Biol. Interact. 2010;188(1):220-227.
  • 25. Li Z, Yang X, Dong S, et al. DNA breakage induced by piceatannol and copper (II): Mechanism and anticancer properties. Oncol Lett. 2012;3(5):1087-1094.
  • 26. Subramaniam S, Vohra I, Iyer A, et al. A paradoxical relationship between resveratrol and copper (II) with respect to degradation of DNA and RNA. F1000Research. 2015;4.
  • 27. Kobayashi T, Guo LL, Nishida Y. Mechanism of double-strand DNA cleavage effected by iron-bleomycin. Z. Naturforsch., C, J. Biosci. 1998;53(9-10):867-870.
  • 28. Ohnishi S, Murata M, Ida N, et al. Oxidative DNA damage induced by metabolites of chloramphenicol, an antibiotic drug. Free Radical Res. 2015;49(9):1165-1172.
  • 29. Oikawa S, Yamada K, Yamashita N, et al. N-acetylcysteine, a cancer chemopreventive agent, causes oxidative damage to cellular and isolated DNA. Carcinogenesis. 1999;20(8):1485-1490.
  • 30. Ogawa K, Hiraku Y, Oikawa S, et al. Molecular mechanisms of DNA damage induced by procarbazine in the presence of Cu (II). Mutat Res Genet Toxicol Environ Mutagen. 2003;539(1-2):145-155.
  • 31. Isidori M, Nardelli A, Pascarella L, et al. Toxic and genotoxic impact of fibrates and their photoproducts on non-target organisms. Environ. Int. 2007;33(5):635-641.
  • 32. Maiguma T, Fujisaki K, Itoh Y, et al. Cell-specific toxicity of fibrates in human embryonal rhabdomyosarcoma cells. Naunyn-Schmiedeberg's Arch. Pharmacol. 2003;367(3):289-296.
  • 33. Tounekti O, Belehradek Jr J, Mir L. Relationships between DNA fragmentation, chromatin condensation, and changes in flow cytometry profiles detected during apoptosis. Exp. Cell Res. 1995;217(2):506-516.
  • 34. Topaktas M, Kafkas N, Sadighazadi S, et al. In vitro cytogenetic toxicity of bezafibrate in human peripheral blood lymphocytes. Cytotechnology. 2017;69(4):579-589.
  • 35. Abd TT, Jacobson TA. Statin-induced myopathy: a review and update. Expert Opin. Drug Saf. 2011;10(3):373-387.
  • 36. Ariad S, Hechtlinger V. Bezafibrate‐induced neutropenia. Eur. J. Haematol. 1993;50(3):179-179.
  • 37. Kacirova I, Grundmann M. Fenofibrate-induced Anemia and Neutropenia–a case report. Clin. Ther. 2015;37(8):e103.
  • 38. Shaikh SA, Ahmed SR, Jayaram B. A molecular thermodynamic view of DNA–drug interactions: a case study of 25 minor-groove binders. Arch. Biochem. Biophys. 2004;429(1):81-99.
  • 39. Banduhn N, Obe G. Mutagenicity of methyl 2-benzimidazolecarbamate, diethylstilbestrol and estradiol: structural chromosomal aberrations, sister-chromatid exchanges, C-mitoses, polyploidies and micronuclei. Mutat Res Genet Toxicol Environ Mutagen. 1985;156(3):199-218.

Bezafibrat’ın Demir ve Bakır Varlığında Deoksiribonükleik Asit Üzerine Etkisi

Year 2019, Volume: 3 Issue: 3, 131 - 136, 31.12.2019

Abstract

Amaç: Bezafibrat genellikle hiperlipidemi ve diyabetik hastaları tedavi etmek için kullanılır. Kimyasal ve ilaçların demir ve bakır varlığında DNA üzerindeki etkilerinin analizi, tıbbi araştırmalarda çok önem arz etmektedir. Bu nedenle, bu araştırma bezafibratın DNA üzerindeki etkisini demir ve bakır varlığında analiz etmeyi amaçlamıştır.  

Gereç ve Yöntemler: Süpersarmal pUC19 plazmid DNA bakır, demir ve bakır artı hidrojen peroksit varlığında Bezafibrat’ın farklı derişimleri (2,6 - 1,3 - 0,13 - 0,013 ve 0,0013 mM) ile muamele edildi, ardından agaroz jeli (% 1) elektroforezinde analiz edildi.

Bulgular: Bezafibrat derişimlerinin hiçbirinin FeS04 ve CuCl2 varlığında DNA’yı kıramadığı gözlemlendi. Muamele edilen Süpersarmal DNA’nın band yoğunluğu ve parlaklığı kontrol örnekler ile karşılaştırıldığında hiçbir fark görülmedi. Her ne kadar 0,13 – 0,013 ve 0,0013 mM Bezafibrat DNA’yı hidrojen radikallerine karşı koruyamasa da, ilacın 2,6 – 1,3 mM’si derişimine bağlı olarak DNA’yı koruyabildiği gözlemlendi.

Sonuç: Bizim Çalışmamız bezafibratın DNA fragmantasyonu üzerindeki zararlı etkisinin dolaylı bir şekilde olabileceğini göstermektedir.

Project Number

2018-50737594-01

References

  • 1. Robins SJ. PPARα ligands and clinical trials: cardiovascular risk reduction with fibrates. J. Cardiovasc. Risk. 2001;8(4):195-201.
  • 2. Grygiel-Górniak B. Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications-a review. Nutr J. 2014;13(1):17-25.
  • 3. Franko A, Huypens P, Neschen S, et al. Bezafibrate improves insulin sensitivity and metabolic flexibility in STZ-induced diabetic mice. Diabetes. 2016;65(9):2540-2552.
  • 4. Erem C. Prevalence of overweight and obesity in Turkey. IJC Metab Endocr . 2015;8:38-41.
  • 5. Siramshetty VB, Nickel J, Omieczynski C, et al. Withdrawn—a resource for withdrawn and discontinued drugs. Nucleic Acids Res. 2015;44(D1):D1080-D1086.
  • 6. Rocco L, Peluso C, Cesaroni F, et al. Genomic damage in human sperm cells exposed in vitro to environmental pollutants. J. Environment Analytic Toxicol. 2012;2(117):10.4172.
  • 7. Tawfeeq MM, Suzuki T, Shimamoto K, et al. Evaluation of in vivo genotoxic potential of fenofibrate in rats subjected to two-week repeated oral administration. Arch. Toxicol. 2011;85(8):1003-1011.
  • 8. Davis JD, Lin S-Y. DNA damage and breast cancer. World J Clin Oncol. 2011;2(9):329.
  • 9. Sharpe C, Collet J, Belzile E, et al. The effects of tricyclic antidepressants on breast cancer risk. Br. J. Cancer. 2002;86(1):92.
  • 10. Bertoncini C, Meneghini R, Galembeck F, et al. Preferential Localization of Iron in The Chromatin of Fe-Enriched Cells Is Linked to DNA Cleavage Sites and Control of Carcinogenesis. J. Cancer Sci. Ther. 2016;8:213-215.
  • 11. Brewer GJ. Risks of copper and iron toxicity during aging in humans. Chem. Res. Toxicol. 2009;23(2):319-326.
  • 12. Alexander DD, Weed DL, Cushing CA, et al. Meta-analysis of prospective studies of red meat consumption and colorectal cancer. Eur. J. Cancer Prev. 2011;20(4):293-307.
  • 13. Guo J, Wei W, Zhan L. Red and processed meat intake and risk of breast cancer: a meta-analysis of prospective studies. Breast Cancer Res. Treat. 2015;151(1):191-198.
  • 14. Zhu H-C, Yang X, Xu L-P, et al. Meat consumption is associated with esophageal cancer risk in a meat-and cancer-histological-type dependent manner. Dig. Dis. Sci. 2014;59(3):664-673.
  • 15. Xue X-J, Gao Q, Qiao J-H, et al. Red and processed meat consumption and the risk of lung cancer: a dose-response meta-analysis of 33 published studies. Int. J. Clin. Exp. Med. 2014;7(6):1542.
  • 16. Zhang X, Yang Q. Association between serum copper levels and lung cancer risk: A meta-analysis. J. Int. Med. Res. 2018;46(12):4863-4873.
  • 17. Zhang M, Shi M, Zhao Y. Association between serum copper levels and cervical cancer risk: A meta-analysis. Biosci. Rep. 2018;38(4):BSR20180161.
  • 18. Yi Z-C, Liu Y-Z, Li H-X, et al. Chebulinic acid and tellimagrandin I inhibit DNA strand breaks by hydroquinone/Cu (II) and H2O2/Cu (II), but potentiate DNA strand breaks by H2O2/Fe (II). Toxicol In Vitro. 2009;23(4):667-673.
  • 19. Coban B, Yildiz U. DNA-binding studies and antitumor evaluation of novel water soluble organic pip and hpip analogs. Appl. Biochem. Biotechnol. 2014;172(1):248-262.
  • 20. Li Y, Zheng Y, Zhang Y, et al. Antioxidant Activity of Coconut (Cocos nucifera L.) Protein Fractions. Molecules. 2018;23(3):1-11.
  • 21. Valipour R, Yilmaz MB, Valipour E. Study of DNA-Binding Activity and Antibacterial Effect of Escitalopram Oxalate, an Extensively Prescribed Antidepressant. Drug Res (Stuttg). 2019.
  • 22. De Mattos J, Dantas F, Caldeira‐de‐Araújo A, et al. Agarose gel electrophoresis system in the classroom: detection of DNA strand breaks through the alteration of plasmid topology. Biochem. Mol. Biol. Educ. 2004;32(4):254-257.
  • 23. Moreno RG, Alipázaga MV, Gomes OF, et al. DNA damage and 2′-deoxyguanosine oxidation induced by S (IV) autoxidation catalyzed by copper (II) tetraglycine complexes: synergistic effect of a second metal ion. J. Inorg. Biochem. 2007;101(5):866-875.
  • 24. Letelier ME, Sánchez-Jofré S, Peredo-Silva L, et al. Mechanisms underlying iron and copper ions toxicity in biological systems: Pro-oxidant activity and protein-binding effects. Chem. Biol. Interact. 2010;188(1):220-227.
  • 25. Li Z, Yang X, Dong S, et al. DNA breakage induced by piceatannol and copper (II): Mechanism and anticancer properties. Oncol Lett. 2012;3(5):1087-1094.
  • 26. Subramaniam S, Vohra I, Iyer A, et al. A paradoxical relationship between resveratrol and copper (II) with respect to degradation of DNA and RNA. F1000Research. 2015;4.
  • 27. Kobayashi T, Guo LL, Nishida Y. Mechanism of double-strand DNA cleavage effected by iron-bleomycin. Z. Naturforsch., C, J. Biosci. 1998;53(9-10):867-870.
  • 28. Ohnishi S, Murata M, Ida N, et al. Oxidative DNA damage induced by metabolites of chloramphenicol, an antibiotic drug. Free Radical Res. 2015;49(9):1165-1172.
  • 29. Oikawa S, Yamada K, Yamashita N, et al. N-acetylcysteine, a cancer chemopreventive agent, causes oxidative damage to cellular and isolated DNA. Carcinogenesis. 1999;20(8):1485-1490.
  • 30. Ogawa K, Hiraku Y, Oikawa S, et al. Molecular mechanisms of DNA damage induced by procarbazine in the presence of Cu (II). Mutat Res Genet Toxicol Environ Mutagen. 2003;539(1-2):145-155.
  • 31. Isidori M, Nardelli A, Pascarella L, et al. Toxic and genotoxic impact of fibrates and their photoproducts on non-target organisms. Environ. Int. 2007;33(5):635-641.
  • 32. Maiguma T, Fujisaki K, Itoh Y, et al. Cell-specific toxicity of fibrates in human embryonal rhabdomyosarcoma cells. Naunyn-Schmiedeberg's Arch. Pharmacol. 2003;367(3):289-296.
  • 33. Tounekti O, Belehradek Jr J, Mir L. Relationships between DNA fragmentation, chromatin condensation, and changes in flow cytometry profiles detected during apoptosis. Exp. Cell Res. 1995;217(2):506-516.
  • 34. Topaktas M, Kafkas N, Sadighazadi S, et al. In vitro cytogenetic toxicity of bezafibrate in human peripheral blood lymphocytes. Cytotechnology. 2017;69(4):579-589.
  • 35. Abd TT, Jacobson TA. Statin-induced myopathy: a review and update. Expert Opin. Drug Saf. 2011;10(3):373-387.
  • 36. Ariad S, Hechtlinger V. Bezafibrate‐induced neutropenia. Eur. J. Haematol. 1993;50(3):179-179.
  • 37. Kacirova I, Grundmann M. Fenofibrate-induced Anemia and Neutropenia–a case report. Clin. Ther. 2015;37(8):e103.
  • 38. Shaikh SA, Ahmed SR, Jayaram B. A molecular thermodynamic view of DNA–drug interactions: a case study of 25 minor-groove binders. Arch. Biochem. Biophys. 2004;429(1):81-99.
  • 39. Banduhn N, Obe G. Mutagenicity of methyl 2-benzimidazolecarbamate, diethylstilbestrol and estradiol: structural chromosomal aberrations, sister-chromatid exchanges, C-mitoses, polyploidies and micronuclei. Mutat Res Genet Toxicol Environ Mutagen. 1985;156(3):199-218.
There are 39 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Research Article
Authors

Ebrahim Valipour 0000-0003-4603-7602

Project Number 2018-50737594-01
Publication Date December 31, 2019
Acceptance Date October 28, 2019
Published in Issue Year 2019 Volume: 3 Issue: 3

Cite

APA Valipour, E. (2019). Effect of Bezafibrate on Deoxyribonucleic Acid in the Presence of Iron and Copper. Turkish Journal of Diabetes and Obesity, 3(3), 131-136.
AMA Valipour E. Effect of Bezafibrate on Deoxyribonucleic Acid in the Presence of Iron and Copper. Turk J Diab Obes. December 2019;3(3):131-136.
Chicago Valipour, Ebrahim. “Effect of Bezafibrate on Deoxyribonucleic Acid in the Presence of Iron and Copper”. Turkish Journal of Diabetes and Obesity 3, no. 3 (December 2019): 131-36.
EndNote Valipour E (December 1, 2019) Effect of Bezafibrate on Deoxyribonucleic Acid in the Presence of Iron and Copper. Turkish Journal of Diabetes and Obesity 3 3 131–136.
IEEE E. Valipour, “Effect of Bezafibrate on Deoxyribonucleic Acid in the Presence of Iron and Copper”, Turk J Diab Obes, vol. 3, no. 3, pp. 131–136, 2019.
ISNAD Valipour, Ebrahim. “Effect of Bezafibrate on Deoxyribonucleic Acid in the Presence of Iron and Copper”. Turkish Journal of Diabetes and Obesity 3/3 (December 2019), 131-136.
JAMA Valipour E. Effect of Bezafibrate on Deoxyribonucleic Acid in the Presence of Iron and Copper. Turk J Diab Obes. 2019;3:131–136.
MLA Valipour, Ebrahim. “Effect of Bezafibrate on Deoxyribonucleic Acid in the Presence of Iron and Copper”. Turkish Journal of Diabetes and Obesity, vol. 3, no. 3, 2019, pp. 131-6.
Vancouver Valipour E. Effect of Bezafibrate on Deoxyribonucleic Acid in the Presence of Iron and Copper. Turk J Diab Obes. 2019;3(3):131-6.

Turkish Journal of Diabetes and Obesity (Turk J Diab Obes) is a scientific publication of Zonguldak Bulent Ecevit University Obesity and Diabetes Research and Application Center.

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