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The Effect of Lycopene on DNA Damage and Repair in Fluoride-Treated NRK-52E Cell Line

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Abstract

Exposure of fluorine at toxic concentrations causes serious damage by accumulating in especially bones, kidneys, and other soft tissues. Fluorine at cytotoxic concentrations may cause DNA damage. This study aims to determine the level of DNA damage due to sodium fluoride (NaF) at different hours (3rd, 12th, and 24th hours) and in IC50 concentrations designated for each hour and reveal the protective effect of lycopene on possible damage. The best enhancer concentrations (1 μM) of microtitration (MTT) viability test and proliferation of lycopene and IC50 values of NaF at the 3rd, 12th, and 24th hour were 9600, 5500, and 3200 μM, respectively. DNA damage significantly increased in all NaF-treated groups in comparison with the control group (p < 0.05). DNA damage due to NaF+LYC application significantly decreased in comparison with the control group (p < 0.05). Lycopene application significantly increased the expression levels of the Ku70 and Ku80 genes which have a part in DNA repair (p < 0.05). The statistical data showed that application of lycopene which is an important antioxidant molecule may be beneficial for decreasing NaF-induced DNA damage. In conclusion, applying lycopene for cytotoxicity due to fluorine in NRK-52E cell line had different effects based on the dosage and time; thus, it can be a potential option for preventing fluorosis-induced toxicity and developing new treatment approaches.

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References

  1. Perumal E, Paul V, Govindarajan V, Panneerselvam L (2013) A brief review on experimental fluorosis. Toxicol Lett 223(2):236–251

    CAS  PubMed  Google Scholar 

  2. Cetin S, Deger Y, Dede S, Yur F (2020) The concentration of certain trace elements in the wool of sheep with fluorosis. Fluoride 53(1 Pt 2):164–169

    CAS  Google Scholar 

  3. Quadri JA, Alam MM, Sarwar S, Singh S, Shariff A, Das TK (2016) Fluoride induced nephrotoxicity: apoptosis, ultrastructural changes and renal tubular injury in experimental animals. Int J Ayurveda Pharma Res 4(8):91–95

    Google Scholar 

  4. Adamek E, Pawłowska-Goral K, Bober K (2005) In vitro and in vivo effects of fluorideions on enzyme activity. Ann Acad Med Stetin 51(2):69–85

    CAS  PubMed  Google Scholar 

  5. Mendoza-Schulz A, Solano-Agama C, Arreola-Mendoza L, Reyes-Marquez B, Barbier O, Del Razo LM, Mendoza-Garrido ME (2009) The effects of fluoride on cell migration, cell proliferation, and cell metabolism in GH4C1 pituitary tumour cells. Toxicol Lett 190(2):179–186

    CAS  PubMed  Google Scholar 

  6. Karahan F, Dede S, Ceylan E (2018) The effect of lycopene treatment on oxidative DNA damage of experimental diabetic rats. Open Clin Biochem J 8:1–6

    Google Scholar 

  7. Bramley PM (2000) Is lycopene benefcial to human health? Phytochemistry 54:233–236

    CAS  PubMed  Google Scholar 

  8. Mashima R, Witting PK, Stocker R (2001) Oxidants and antioxidants in atherosclerosis. Curr Opin Lipidol 12(4):411–418

    CAS  PubMed  Google Scholar 

  9. Yegin SÇ, Yur F (2019) The effect of lycopene application on the antioxidant activity in liver and kidney tissues of diabetic rats. Atatürk Univ J Vet Sci 14(2):119–128

    Google Scholar 

  10. Pennisi R, Ascenzi P, di Masi A (2015) Hsp90: a new player in DNA repair? Biomolecules 5(4):2589–2618

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Fell VL, Schild-Poulter C (2011) Ku regulates signaling to DNA damage response pathways through the Ku70 von Willebrand a domain. Mol Cell Biol 32(1):76–87

    PubMed  Google Scholar 

  12. Burkle A (2001) Poly(APD-ribosyl)ation, a DNA damage-driven protein modification and regulator of genomic instability. Cancer Lett 163(1):1–5

    CAS  PubMed  Google Scholar 

  13. Tice RR, Furedi-Machacek M, Satterfield D, Udumudi A, Vasquez M, Dunnick JK (1998) Measurement of micronucleated erythrocytes and DNA damage during chronic ingestion of phenolphthalein in transgenic female mice heterozygous for the p53 gene. Environ Mol Mutagen 31:113–124

    CAS  PubMed  Google Scholar 

  14. Cetin S, Yur F, Taşpınar M, Dede S, Yüksek V (2017) The effects of lycopene application on sodium fluoride (NaF) applied renal cell line. Int J Second Metab 4(3):508–511

    Google Scholar 

  15. García O, Romero I, González JE, Moreno DL, Cuétara E, Rivero Y, Gutiérrez A, Pérez CL, Alvarez A, Carnesolta D, Guevara I (2011) Visual estimation of the percentage of DNA in the tail in the comet assay: evaluation of different approaches in an intercomparison exercise. Mutat Res 720(1-2):14–21

    PubMed  Google Scholar 

  16. Chomczynski P, Mackey K (1995) Modification of the TRI reagent procedure for isolation of RNA from polysaccharide- and proteoglycan-rich sources. Biotechniques 19(6):942–945

    CAS  PubMed  Google Scholar 

  17. Livak KJ, Schmitten TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and 2(Delta Delta C(T)) method. Methods 25(4):402–408

    CAS  PubMed  Google Scholar 

  18. He LF, Chen JG (2006) DNA damage, apoptosis and cell cycle changes induced by fluoride in rat oral mucosal cells and hepatocytes. World J Gastroenterol 12(7):1144–1148

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Li Y, Liang CK, Katz BP, Brizendine EJ, Stookey GK (1995) Long-term exposure to fluoride in drinking water and sister chromatid exchange frequency in human blood lymphocytes. J Dent Res 74(8):1468–1474

    CAS  PubMed  Google Scholar 

  20. Ribeiro DA, Alves de Lima PL, Marques ME, Salvadori DM (2006) Lack of DNA damage induced byfluoride on mouse lymphoma and human fibroblast cells by single cell gel (comet) assay. Braz Dent J 17(2):91–94

    PubMed  Google Scholar 

  21. Leite Ade L, Santiago JF Jr, Levy FM, Maria AG, Fernandes Mda S, Salvadori DMDA, Buzalaf MA (2007) Absence of DNA damage in multiple organs (blood, liver, kidney, thyroid gland and urinary bladder) afteracute fluoride exposure in rat. Hum Exp Toxicol 26(5):435–440

    PubMed  Google Scholar 

  22. Wang YY, Zhao BL, Li XJ, Su Z, Xi WJ (1997) Spin trapping technique studies onactive oxygen radicals from human polymorphonuclear leukocytes during fluoride stimulated respiratory burst. Fluoride 30(1):5–15

    CAS  Google Scholar 

  23. Shashi A, Singh JP, Thapar SP (2002) Toxic effect of fluoride on rabbit kidney. Fluoride 35(1):38–50

    CAS  Google Scholar 

  24. Rzeuski R, Chlubek D, Machoy Z (1998) Interactions between fluoride and biological free radical reactions. Fluoride 31:43–45

    CAS  Google Scholar 

  25. Kubota K, Lee DH, Tsuchiya M, Young CS, Everett ET, Martinez-Mier EA, Snead ML, Nguyen L, Urano F, Bartlett JD (2005) Fluoride induces endoplasmic reticulum stress in ameloblasts responsible for dental enamel formation. J Biol Chem 280(24):23194–23202

    CAS  PubMed  Google Scholar 

  26. Watters JL, Satia JA, Kupper LL, Swenberg JA, Schroeder JC, Switzer BR (2007) Associations of antioxidant nutrients and oxidative DNA damage in healthy African American and white adults. Cancer Epidemiol Biomark Prev 16(7):1428–1436

    CAS  Google Scholar 

  27. Azqueta A, Collins AR (2012) Carotenoids and DNA damage. Mutat Res 733(1–2):4–13

    CAS  PubMed  Google Scholar 

  28. Scolastici C, Alves de Lima RO, Barbisan LF, Ferreira AL, Ribeiro DA, Salvadori DM (2007) Lycopene activity against chemically induced DNA damage in Chinese hamster ovary cells. Toxicol in Vitro 21(5):840–845

    CAS  PubMed  Google Scholar 

  29. Devaraj S, Mathur S, Basu A (2008) A dose-response study on the effects of purified lycopene supplementation on biomarkers of oxidative stress. J Am Coll Nutr 27(2):267–273

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Huang CS, Hu ML (2011) Lycopene inhibits DNA damage and reduces hMTH1 mRNA expression in the liver of Mongolian gerbils treated with ferric nitrilotriacetate. Food Chem Toxicol 49(6):1381–1386

    CAS  PubMed  Google Scholar 

  31. Matos HR, Capelozzi VL, Gomes OF, Mascio PD, Medeiros MH (2001) Lycopene inhibitis DNA damage and liver necrosis in rats treated with ferric nitrilotriacetate. Arch Biochem Biophys 396:171–174

    CAS  PubMed  Google Scholar 

  32. Li W, Jiang B, Cao X, Xie Y, Huang T (2017) Protective effect of lycopene on fluoride-induced ameloblasts apoptosis and dental fluorosis through oxidative stress-mediated Caspase pathways. Chem Biol Interact 261(5):27–34

    CAS  PubMed  Google Scholar 

  33. Mansour HH, Tawfik SS (2012) Efficacy of lycopene against fluoride toxicity in rats. Pharm Biol 50(6):707–711

    CAS  PubMed  Google Scholar 

  34. Jothiramajayam M, Sinha S, Ghosh M, Nag A, Jana A, Mukherjee A (2014) Sodium fluoride promotes apoptosis by generation of reactive oxygen species in human lymphocytes. J Toxicol Environ Health A 77(21):1269–1280

    CAS  PubMed  Google Scholar 

  35. Song HG, Gao PJ, Wang FC, Chen YC, Yan YX, Guo M, Wang Y, Huang BF (2014) Sodium floride induces apoptosis in the kidney of rats throughcaspase-mediated pathways and DNA damage. J Physiol Biochem 70:857–868

    CAS  PubMed  Google Scholar 

  36. Zhang Y, Sun X, Sun G, Liu S, Wang L (2006) DNA damage induced by fluoride in rat osteoblasts. Fluoride 39(3):191–194

    Google Scholar 

  37. Otsuki S, Morshed SR, Chowdhury SA, Takayama F, Satoh T, Hashimoto K, Sugiyama K, Amano O, Yasui T, Yokote Y, Akahane K, Sakagami H (2005) Possible link between glycolysis and apoptosis induced by sodium fluoride. J Dent Res 10:919–923

    Google Scholar 

  38. Ito M, Nakagawa H, Okada T, Miyazaki S, Matsuo S (2009) ER-stress caused by accumulated intracistanal granules activates autophagy through a different signal pathway from unfolded protein response in exocrine pancreas cells of rats exposed to flüoride. Arch Toxicol 83(2):151–159

    CAS  PubMed  Google Scholar 

  39. Suzuki M, Bandoski C, Bartlett JD (2015) Fluoride induces oxidative damage and SIRT1/autophagy through ROS-mediated JNK signaling. Free Radic Biol Med 89:369–378

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Jia L, Zhang Z, Zhai L, Zhang Y, Sun G (2008) DNA damage induced by fluoride in rat kidney cells. Fluoride 41(4):297–300

    CAS  Google Scholar 

  41. He H, Wang H, Jiao Y, Ma C, Zhang H, Zhou Z (2015) Effect of sodium fluoride on the proliferation and gene differential expression in human RPMI8226 cells. Biol Trace Elem Res 167(1):11–17

    CAS  PubMed  Google Scholar 

  42. Yüksek V, Dede S, Taşpınar M, Çetin S (2017) The effects of vitamins a, D, E, and C on apoptosis and DNA damage in sodium fluoride-treated renal and osteoblast cell lines. Fluoride 50(3):300–313

    Google Scholar 

  43. Cetin S, Yur F, Taşpinar M, Yüksek V (2019) The effects of some minerals on apoptosis and DNA damage in sodium fluoride-administered renal and osteoblast cell lines. Fluoride 52(3):362–378

    CAS  Google Scholar 

  44. Do K, Chen AP (2012) Molecular pathways: targeting PARP in cancer treatment. Clin Cancer Res 19(5):977–984

    PubMed  PubMed Central  Google Scholar 

  45. Nilov D, Maluchenko N, Kurgina T, Pushkarev S, Lys A, Kutuzov M, Gerasimova N, Feofanov A, Švedas V, Lavrik O, Studitsky VM (2020) Molecular mechanisms of PARP-1 inhibitor 7-methylguanine. Int J Mol Sci 20:21(6)

    Google Scholar 

  46. Yang S, Zhang L, Ke M, Qian W, Zhang Z (2013) Effect of selenium ıntervention on chronic fluorosis-ınduced renal cell apoptosis in rats. Biol Trace Elem Res 153:237–242

    CAS  PubMed  Google Scholar 

  47. Lee JH, Jung JY, Jeong YJ, Park JH, Yang KH, Choi NK, Kim SH, Kim WJ (2008) Involvement of both mitochondrial- and death receptor-dependent apoptotic pathways regulated by Bcl-2 family in sodium fluoride-induced apoptosis of the human gingival fibroblasts. Toxicology 243(3):340–347

    CAS  PubMed  Google Scholar 

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Funding

This study was supported by a grant from the Scientific Research Projects Presidency of Van Yüzüncü Yıl University (Project No: THD-2018-7175).

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Authors and Affiliations

  1. Faculty of Veterinary Medicine, Biochemistry Department, Van Yuzuncu Yil University, Van, Turkey

    Sedat Çetin

  2. Faculty of Science, Chemistry Department, Van Yuzuncu Yil University, Van, Turkey

    Ayşe Usta

  3. Özalp Vocational High School, Van Yuzuncu Yil University, Van, Turkey

    Veysel Yüksek

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  1. Sedat Çetin
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  2. Ayşe Usta
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  3. Veysel Yüksek
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Correspondence to Sedat Çetin.

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Çetin, S., Usta, A. & Yüksek, V. The Effect of Lycopene on DNA Damage and Repair in Fluoride-Treated NRK-52E Cell Line. Biol Trace Elem Res 199, 1979–1985 (2021). https://doi.org/10.1007/s12011-020-02288-4

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  • DOI: https://doi.org/10.1007/s12011-020-02288-4

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