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Evaluation of the Antigenotoxic Effect of Quercetin Against Antiepileptic Drug Genotoxicity by Comet Analysis

Year 2023, Volume: 27 Issue: 6, 1185 - 1196, 18.12.2023
https://doi.org/10.16984/saufenbilder.1339199

Abstract

Valproic acid (VPA) is among the most commonly used antiepileptic drugs in childhood and adult epilepsy. Although VPA is well tolerated, it can cause life-threatening side effects. VPA has toxic and genotoxic effects. Antioxidants can reverse drugs' toxic and genotoxic effects. Therefore, our study aimed to evaluate the antigenotoxic protective effect of quercetin (QUE) against VPA genotoxicity by in vitro comet assay analysis method. Comet assay analysis was performed in five different groups. Group I; negative control (Sterile H2O), Group II; positive control (H2O2), Group III; VPA was applied in four different dose ranges, Group IV; QUE was applied in four different dose ranges, Group V; For the simultaneous combined administration of VPA and QUE, three different doses of VPA + four different doses of QUE were administered. Low-dose administration of QUE was more effective in ameliorating the damage caused by low-dose VPA (62.5 μg/ml) administration. It is seen that the genotoxic damage caused by the application of 125 μg/ml VPA can be eliminated by QUE at all doses. It was determined that different doses of QUE exhibited a significant antigenotoxic effect against damage caused by 125 µg/mL VPA (P<0.05). In our study, the curative effect of QUE on DNA damage was determined by in vitro comet analysis. Our analysis results showed that QUE ameliorates VPA-induced genetic damage.

References

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  • [2] D. A. Colak, C. Ersöz, “Sisplatin ve valproik asitin indüklediği toksisiteye karşı kudret narının Drosophila melanogaster’in yaşama yüzdesi ve ömür uzunluğu üzerine etkisi,” Eurasian Journal of Biological and Chemical Sciences, vol.2, no.2, pp.73- 78, 2018.
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  • [9] D. Coulter, “Carnitine deficiency: a possible mechanism for valproate hepatotoxicity,” The Lancet, vol. 323, no. 8378, pp.689, 1984.
  • [10] T. Devasagayam, J. Tilak, K. Boloor, K. S. Sane, S. S. Ghaskadbi, R. Lele, “Free radicals and antioxidants in human health: current status and future prospects,” Journal of the Association of Physicians of India, vol. 52, no.10, pp.794-804, 2004.
  • [11] A. S. Yalçın, A. M. Yılmaz, E. M. Altundag, S. Koçtürk, “Kurkumin, kuersetin ve çay kateşinlerinin antikanser etkileri,” Marmara Pharmaceutical Journal, vol. 21, no.1, pp. 19-29, 2017.
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  • [15] N. P. Singh, M. T. McCoy, R. R. Tice, E. L. Schneider, “Simple technique for quantitation of low levels of DNA damage in individual cells,” Experimental Cell Research, vol 175, no. 1, pp.184-191, 1988.
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  • [17] L. Hu, X. Lu, B. Lu, Y. Huang, “The effect of valproic acid on SCE and chromosome aberrations in epileptic children,” Mutation Research Letters, vol. 243, no. 1, pp. 63-66, 1990.
  • [18] I. Karapidaki, M. T. Ekonomopoulou, K. Akritopoulou, D. Anestakis, Z. Iakovidou-Kritsi, “Cytogenetic effects of valproic acid and ziprasidone in human lymphocyte cultures,” Neuropsychobiology, vol. 64, no. 4, pp. 219-223, 2011.
  • [19] A. T. Mahmoud, M. A. Tawfik, S. A. Abd-El-Naby, D. A. E. A. Hammad, “A study of DNA damage in epileptic children treated with valproic acid or carbamazepine,” Menoufia Medical Journal, vol. 32, no. 3, pp. 1078, 2019.
  • [20] S. Khan, T. Ahmad, C. V. Parekh, P. P. Trivedi, S. Kushwaha, G. Jena, “Investigation on sodium valproate induced germ cell damage, oxidative stress and genotoxicity in male Swiss mice,” Reproductive Toxicology, vol. 32, no. 4, pp. 385-394, 2011.
  • [21] M. Denli, H. I. Aydin, R. Döndaröz, T. Özişik, E. Erdem, V. Baltaci, “Genotoxicity evaluation in female patients on valproic acid monotherapy using alkaline single cell gel electrophoresis (comet assay),” Eastern Journal of Medicine, vol. 5, no. 2, pp.61-65, 2000.
  • [22] S. A. Sakr, M. E. Zowail, A. M. Marzouk, “Effect of saffron (Crocus sativus L.) on sodium valproate induced cytogenetic and testicular alterations in albino rats,” Anatomy & cell biology, vol. 47, no. 3, pp. 171-179, 2014.
  • [23] M. Russo, C. Spagnuolo, I. Tedesco, S. Bilotto, G. L. Russo, “The flavonoid quercetin in disease prevention and therapy: facts and fancies,” Biochemical pharmacology, vol. 83, no. 1, pp. 6-15, 2012.
  • [24] D. Nieoczym, K. Socała, G. Raszewski, P. Wlaź, “Effect of quercetin and rutin in some acute seizure models in mice,” Progress in NeuroPsychopharmacology and Biological Psychiatry, vol. 54, pp. 50-58, 2014.
  • [25] S. Chaudhary, P. Ganjoo, S. Raiusddin, S. Parvez, “Nephroprotective activities of quercetin with potential relevance to oxidative stress induced by valproic acid,” Protoplasma, vol. 252, pp. 209- 217, 2015.
  • [26] A. A. Ramos, C. F. Lima, M. L. Pereira, M. Fernandes-Ferreira, C. PereiraWilson, “Antigenotoxic effects of quercetin, rutin and ursolic acid on HepG2 cells: evaluation by the comet assay,” Toxicology Letters, vol. 177, no. 1, pp. 66-73, 2008.
Year 2023, Volume: 27 Issue: 6, 1185 - 1196, 18.12.2023
https://doi.org/10.16984/saufenbilder.1339199

Abstract

References

  • [1] P. Haznedar, “Çocukluk çağı epilepsilerinde levetirasetam ve valproik asit tedavisinin karaciğer fonksiyonları, plazma serbest karnitin ve lipid peroksidasyonu ile oksidatif DNA hasarı üzerine etkileri,” Çocuk Sağlığı ve Hastalıkları Anabilim Dalı Tıpta Uzmanlık Tezi, Ankara üniversitesi, 2017.
  • [2] D. A. Colak, C. Ersöz, “Sisplatin ve valproik asitin indüklediği toksisiteye karşı kudret narının Drosophila melanogaster’in yaşama yüzdesi ve ömür uzunluğu üzerine etkisi,” Eurasian Journal of Biological and Chemical Sciences, vol.2, no.2, pp.73- 78, 2018.
  • [3] T. Tomson, D. Battino, E. Perucca, “Valproic acid after five decades of use in epilepsy: time to reconsider the indications of a time-honored drug,” Lancet Neurology, vol.15, no.2, pp.210-218, 2016.
  • [4] M. D. Sztajnkrycer, “Valproic acid toxicity: overview and management,” Journal of Toxicology: Clinical Toxicology, vol. 40, no. 6, pp.789-801, 2002.
  • [5] I. T. Okay, C. Kısa, N. Dilbaz, “Psikiyatrik bozukluklarda valproat kullanımı”, Klinik Psikiyatri, vol. 5, 33- 41, 2002.
  • [6] C. Hiemke, P. Baumann, N. Bergemann, A. Conca, O. Dietmaier, K. Egberts, M. Fric, M. Gerlach, C. Greiner, G. Grunder, E. Halen, U. Havemann-Reinecke, E. Jaquenoud Sirot, H. Kircherr, G. Laux, U.C. Lutz, T. Messer, M.J. Müller, B. Pfuhlmann, B. Rambeck, P. Riederer, B. Schoppek, J. Stingl, M. Uhr, S. Ulrich, R. Waschgler, G. Zernig, “AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: update 2011”, Pharmacopsychiatry, vol. 44, no. 06, pp.195-235, 2011.
  • [7] F. E. Dreifuss, N. Santilli, D. H. Langer, K. P. Sweeney, K. A. Moline, K. B. Menander, “Valproic acid hepatic fatalities: a retrospective review,” Neurology, vol. 37, no. 3, pp. 379-85, 1987.
  • [8] F. J. Romero, F. Bosch-Morell, M. J. Romero, E. J. Jareño, B. Romero, N. Marín, J. Romá, “Lipid peroxidation products and antioxidants in human disease,” Environmental Health Perspectives, vol. 106, no. 5, pp. 1229, 1998.
  • [9] D. Coulter, “Carnitine deficiency: a possible mechanism for valproate hepatotoxicity,” The Lancet, vol. 323, no. 8378, pp.689, 1984.
  • [10] T. Devasagayam, J. Tilak, K. Boloor, K. S. Sane, S. S. Ghaskadbi, R. Lele, “Free radicals and antioxidants in human health: current status and future prospects,” Journal of the Association of Physicians of India, vol. 52, no.10, pp.794-804, 2004.
  • [11] A. S. Yalçın, A. M. Yılmaz, E. M. Altundag, S. Koçtürk, “Kurkumin, kuersetin ve çay kateşinlerinin antikanser etkileri,” Marmara Pharmaceutical Journal, vol. 21, no.1, pp. 19-29, 2017.
  • [12] Y. J. Moon, I. Wang, R. DiCenzo, M. E. Morris, “Quercetin pharmacokinetics in humans,” Biopharmaceutics and Drug Disposition, vol. 29, pp. 205-17, 2008.
  • [13] W. Bors, W. Heller, C. Michel, M. Saran, “Flavonoids as antioxidants: determination of radical-scavenging efficiencies,” Methods in Enzymology, vol. 186, pp. 343–55, 1990.
  • [14] S. L. Patil, K. Swaroop, N. Kakde, H. M. Somashekarappa, “In vitro protective effect of rutin and quercetin against radiation-induced genetic damage in human lymphocytes,” Indian Journal of Nuclear Medicine, vol. 32, no. 4, pp. 289, 2017.
  • [15] N. P. Singh, M. T. McCoy, R. R. Tice, E. L. Schneider, “Simple technique for quantitation of low levels of DNA damage in individual cells,” Experimental Cell Research, vol 175, no. 1, pp.184-191, 1988.
  • [16] S. Şardaş, M. Ada, A.E. Karakaya, N. Aydin, “Sister-chromatid exchanges in epileptic patients on anticonvulsant therapy,” Mutation Research/Environmental Mutagenesis and Related Subjects, vol. 313, no. 1, pp. 21-24, 1994.
  • [17] L. Hu, X. Lu, B. Lu, Y. Huang, “The effect of valproic acid on SCE and chromosome aberrations in epileptic children,” Mutation Research Letters, vol. 243, no. 1, pp. 63-66, 1990.
  • [18] I. Karapidaki, M. T. Ekonomopoulou, K. Akritopoulou, D. Anestakis, Z. Iakovidou-Kritsi, “Cytogenetic effects of valproic acid and ziprasidone in human lymphocyte cultures,” Neuropsychobiology, vol. 64, no. 4, pp. 219-223, 2011.
  • [19] A. T. Mahmoud, M. A. Tawfik, S. A. Abd-El-Naby, D. A. E. A. Hammad, “A study of DNA damage in epileptic children treated with valproic acid or carbamazepine,” Menoufia Medical Journal, vol. 32, no. 3, pp. 1078, 2019.
  • [20] S. Khan, T. Ahmad, C. V. Parekh, P. P. Trivedi, S. Kushwaha, G. Jena, “Investigation on sodium valproate induced germ cell damage, oxidative stress and genotoxicity in male Swiss mice,” Reproductive Toxicology, vol. 32, no. 4, pp. 385-394, 2011.
  • [21] M. Denli, H. I. Aydin, R. Döndaröz, T. Özişik, E. Erdem, V. Baltaci, “Genotoxicity evaluation in female patients on valproic acid monotherapy using alkaline single cell gel electrophoresis (comet assay),” Eastern Journal of Medicine, vol. 5, no. 2, pp.61-65, 2000.
  • [22] S. A. Sakr, M. E. Zowail, A. M. Marzouk, “Effect of saffron (Crocus sativus L.) on sodium valproate induced cytogenetic and testicular alterations in albino rats,” Anatomy & cell biology, vol. 47, no. 3, pp. 171-179, 2014.
  • [23] M. Russo, C. Spagnuolo, I. Tedesco, S. Bilotto, G. L. Russo, “The flavonoid quercetin in disease prevention and therapy: facts and fancies,” Biochemical pharmacology, vol. 83, no. 1, pp. 6-15, 2012.
  • [24] D. Nieoczym, K. Socała, G. Raszewski, P. Wlaź, “Effect of quercetin and rutin in some acute seizure models in mice,” Progress in NeuroPsychopharmacology and Biological Psychiatry, vol. 54, pp. 50-58, 2014.
  • [25] S. Chaudhary, P. Ganjoo, S. Raiusddin, S. Parvez, “Nephroprotective activities of quercetin with potential relevance to oxidative stress induced by valproic acid,” Protoplasma, vol. 252, pp. 209- 217, 2015.
  • [26] A. A. Ramos, C. F. Lima, M. L. Pereira, M. Fernandes-Ferreira, C. PereiraWilson, “Antigenotoxic effects of quercetin, rutin and ursolic acid on HepG2 cells: evaluation by the comet assay,” Toxicology Letters, vol. 177, no. 1, pp. 66-73, 2008.

Details

Primary Language English
Subjects Biochemistry and Cell Biology (Other)
Journal Section Research Articles
Authors

Fadime CANBOLAT 0000-0001-6759-7735

Nihan AKINCI KENANOĞLU 0000-0002-3917-6412

Tuğba Nurcan YÜKSEL 0000-0001-5092-1674

Ahmet Ali BERBER 0000-0002-2036-6929

Early Pub Date December 1, 2023
Publication Date December 18, 2023
Submission Date August 7, 2023
Acceptance Date October 3, 2023
Published in Issue Year 2023 Volume: 27 Issue: 6

Cite

APA CANBOLAT, F., AKINCI KENANOĞLU, N., YÜKSEL, T. N., BERBER, A. A. (2023). Evaluation of the Antigenotoxic Effect of Quercetin Against Antiepileptic Drug Genotoxicity by Comet Analysis. Sakarya University Journal of Science, 27(6), 1185-1196. https://doi.org/10.16984/saufenbilder.1339199
AMA CANBOLAT F, AKINCI KENANOĞLU N, YÜKSEL TN, BERBER AA. Evaluation of the Antigenotoxic Effect of Quercetin Against Antiepileptic Drug Genotoxicity by Comet Analysis. SAUJS. December 2023;27(6):1185-1196. doi:10.16984/saufenbilder.1339199
Chicago CANBOLAT, Fadime, Nihan AKINCI KENANOĞLU, Tuğba Nurcan YÜKSEL, and Ahmet Ali BERBER. “Evaluation of the Antigenotoxic Effect of Quercetin Against Antiepileptic Drug Genotoxicity by Comet Analysis”. Sakarya University Journal of Science 27, no. 6 (December 2023): 1185-96. https://doi.org/10.16984/saufenbilder.1339199.
EndNote CANBOLAT F, AKINCI KENANOĞLU N, YÜKSEL TN, BERBER AA (December 1, 2023) Evaluation of the Antigenotoxic Effect of Quercetin Against Antiepileptic Drug Genotoxicity by Comet Analysis. Sakarya University Journal of Science 27 6 1185–1196.
IEEE F. CANBOLAT, N. AKINCI KENANOĞLU, T. N. YÜKSEL, and A. A. BERBER, “Evaluation of the Antigenotoxic Effect of Quercetin Against Antiepileptic Drug Genotoxicity by Comet Analysis”, SAUJS, vol. 27, no. 6, pp. 1185–1196, 2023, doi: 10.16984/saufenbilder.1339199.
ISNAD CANBOLAT, Fadime et al. “Evaluation of the Antigenotoxic Effect of Quercetin Against Antiepileptic Drug Genotoxicity by Comet Analysis”. Sakarya University Journal of Science 27/6 (December 2023), 1185-1196. https://doi.org/10.16984/saufenbilder.1339199.
JAMA CANBOLAT F, AKINCI KENANOĞLU N, YÜKSEL TN, BERBER AA. Evaluation of the Antigenotoxic Effect of Quercetin Against Antiepileptic Drug Genotoxicity by Comet Analysis. SAUJS. 2023;27:1185–1196.
MLA CANBOLAT, Fadime et al. “Evaluation of the Antigenotoxic Effect of Quercetin Against Antiepileptic Drug Genotoxicity by Comet Analysis”. Sakarya University Journal of Science, vol. 27, no. 6, 2023, pp. 1185-96, doi:10.16984/saufenbilder.1339199.
Vancouver CANBOLAT F, AKINCI KENANOĞLU N, YÜKSEL TN, BERBER AA. Evaluation of the Antigenotoxic Effect of Quercetin Against Antiepileptic Drug Genotoxicity by Comet Analysis. SAUJS. 2023;27(6):1185-96.

Sakarya University Journal of Science (SAUJS)