Login Register Cart 0
Generic placeholder image

Current Molecular Pharmacology

Editor-in-Chief

ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Reduction of Genotoxicity of Carbamazepine to Human Lymphocytes by Pre-treatment with Vitamin B12

Author(s): Eman K. Hendawi, Omar F. Khabour*, Laith N. Al-Eitan and Karem H. Alzoubi

Volume 16, Issue 2, 2023

Published on: 01 August, 2022

Article ID: e200422203864 Pages: 6

DOI: 10.2174/1874467215666220420135924

Price: $65

Open Access Journals Promotions 2
conference banner
Abstract

Background: Carbamazepine (CBZ) is widely used as an anti-epileptic drug. Vitamin B12 has been shown to protect against DNA damage caused by several mutagenic agents.

Objective: This study aimed to investigate the effect of vitamin B12 on CBZ-induced genotoxicity in cultured human lymphocytes.

Methods: Sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) genotoxic assays were utilized to achieve the study objective.

Results: The results showed significantly higher frequencies of CAs and SCEs in the CBZ-treated cultures (12 μg/mL) compared to the control group (P<0.01). The genotoxic effects of CBZ were reduced by pre-treatment of cultures with vitamin B12 (13.5μg/ml, P<0.05). Neither CBZ nor vitamin B-12 showed any effects on mitotic and proliferative indices.

Conclusion: CBZ is genotoxic to lymphocyte cells, and this genotoxicity can be reduced by vitamin B12.

Keywords: Carbamazepine, vitamin B12, sister chromatid exchanges, DNA damage, chromosomal aberrations, genotoxicity, white lymphocytes.

Graphical Abstract

[1]
Milburn-McNulty, P.; Panebianco, M.; Marson, A.G. Sulthiame monotherapy for epilepsy. Cochrane Database Syst. Rev., 2021, 9(9), CD010062.
[PMID: 34554571]
[2]
Karaźniewicz-Łada, M.; Główka, A.K. Pharmacokinetic drug-drug interactions among antiepileptic drugs, including CBD, drugs used to treat COVID-19 and nutrients. Int. J. Mol. Sci., 2021, 22(17), 9582.
[3]
Grunze, A.; Amann, B.L. Efficacy of carbamazepine and its derivatives in the treatment of bipolar disorder. Medicina (Kaunas), 2021, 57(5), 433.
[4]
Maan, J.S.; Duong, T.V.H.; Saadabadi, A. StatPearls Publishing LLC.: Treasure Island (FL) , 2021.
[5]
Hakami, T. Neuropharmacology of antiseizure drugs. Neuropsychopharmacol. Rep., 2021, 41(3), 336-351.
[http://dx.doi.org/10.1002/npr2.12196] [PMID: 34296824]
[6]
Khadilkar, S.V.; Patil, V.A. Medical Management of trigeminal neuralgia. Medical management of trigeminal neuralgia. Neurol. India, 2021, 69(Suppl.), S199-S205.
[http://dx.doi.org/10.4103/0028-3886.315996] [PMID: 34003166]
[7]
Day, C.J.; Hardison, R.L.; Spillings, B.L.; Poole, J.; Jurcisek, J.A.; Mak, J.; Jennings, M.P.; Edwards, J.L. Complement receptor 3 mediates HIV-1 transcytosis across an intact cervical epithelial cell barrier: New insight into HIV transmission in women. MBio, 2022, 13(1), e0217721.
[http://dx.doi.org/10.1128/mbio.02177-21] [PMID: 35012346]
[8]
Dokken, K.; Fairley, P. Sodium Channel Blocker Toxicity. [Updated 2022 Apr 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK534844/”
[9]
Rissardo, J.P.; Caprara, A.L.F. Carbamazepine-, oxcarbazepine-, eslicarbazepine-associated movement disorder: A literature review. Clin. Neuropharmacol., 2020, 43(3), 66-80.
[http://dx.doi.org/10.1097/WNF.0000000000000387] [PMID: 32384309]
[10]
Godhwani, N.; Bahna, S.L. Antiepilepsy drugs and the immune system. Ann. Allergy Asthma Immunol., 2016, 117(6), 634-640.
[http://dx.doi.org/10.1016/j.anai.2016.09.443]
[11]
Mifsud, N.A.; Illing, P.T.; Lai, J.W.; Fettke, H.; Hensen, L.; Huang, Z.; Rossjohn, J.; Vivian, J.P.; Kwan, P.; Purcell, A.W. Carbamazepine induces focused T cell responses in resolved stevens-johnson syndrome and toxic epidermal necrolysis cases but does not perturb the immunopeptidome for T cell recognition. Front. Immunol., 2021, 12, 653710.
[http://dx.doi.org/10.3389/fimmu.2021.653710] [PMID: 33912179]
[12]
Awara, W.M.; El-Gohary, M.; El-Nabi, S.H.; Fadel, W.A. In vivo and in vitro evaluation of the mutagenic potential of carbamazepine: Does melatonin have anti-mutagenic activity? Toxicology, 1998, 125(1), 45-52.
[http://dx.doi.org/10.1016/S0300-483X(97)00160-1] [PMID: 9585099]
[13]
Witczak, M.; Kociszewska, I. Wilczyński, J.; Lopaczyńska, D.; Ferenc, T. Evaluation of chromosome aberrations, sister chromatid exchange and micronuclei in cultured cord-blood lymphocytes of newborns of women treated for epilepsy during pregnancy. Mutat. Res., 2010, 701(2), 111-117.
[http://dx.doi.org/10.1016/j.mrgentox.2010.05.003] [PMID: 20466068]
[14]
Yan, S.; Chen, R.; Wang, M.; Zha, J. Carbamazepine at environmentally relevant concentrations caused DNA damage and apoptosis in the liver of Chinese rare minnows (Gobiocypris rarus) by the Ras/Raf/ERK/p53 signaling pathway. Environ. Pollution., 2021, 270, 116245. Change “Environmental Pollution” to “Environ. Pollut.”
[http://dx.doi.org/10.1016/j.envpol.2020.116245]
[15]
Kardoost, M.; Hajizadeh-Saffar, E.; Ghorbanian, M.T.; Ghezelayagh, Z.; Pooshang Bagheri, K.; Behdani, M.; Habibi-Anbouhi, M. Genotoxicity assessment of antiepileptic drugs (AEDs) in human embryonic stem cells. Epilepsy Res., 2019, 158, 106232.
[http://dx.doi.org/10.1016/j.eplepsyres.2019.106232] [PMID: 31707315]
[16]
García-Medina, S.; Galar-Martínez, M.; Gómez-Oliván, L.M.; Torres-Bezaury, R.M.D.C.; Islas-Flores, H.; Gasca-Pérez, E. The relationship between cyto-genotoxic damage and oxidative stress produced by emerging pollutants on a bioindicator organism (Allium cepa): The carbamazepine case. Chemosphere, 2020, 253, 126675.
[http://dx.doi.org/10.1016/j.chemosphere.2020.126675] [PMID: 32278918]
[17]
Ofoegbu, P.U.; Lourenço, J.; Mendo, S.; Soares, A.M.V.M.; Pestana, J.L.T. Effects of low concentrations of psychiatric drugs (carbamazepine and fluoxetine) on the freshwater planarian, Schmidtea mediterranea. Chemosphere, 2019, 217, 542-549.
[http://dx.doi.org/10.1016/j.chemosphere.2018.10.198] [PMID: 30445399]
[18]
Al Amin, A.S.M.; Gupta, V. Vitamin B12 (Cobalamin) [Updated 2022 Apr 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559132/
[19]
Giedyk, M.; Goliszewska, K.; Gryko, D. Vitamin B12 catalysed reactions. Chem. Soc. Rev., 2015, 44(11), 3391-3404.
[http://dx.doi.org/10.1039/C5CS00165J] [PMID: 25945462]
[20]
Khan, K.M.; Jialal, I. I. Folic Acid Deficiency. [Updated 2022 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535377/
[21]
Choi, S.W.; Friso, S.; Ghandour, H.; Bagley, P.J.; Selhub, J.; Mason, J.B. Vitamin B-12 deficiency induces anomalies of base substitution and methylation in the DNA of rat colonic epithelium. J. Nutr., 2004, 134(4), 750-755.
[http://dx.doi.org/10.1093/jn/134.4.750] [PMID: 15051821]
[22]
Fenech, M. Micronutrients and genomic stability: A new paradigm for recommended dietary allowances (RDAs). Food Chem. Toxicol., 2002, 40(8), 1113-1117.
[23]
Fenech, M. Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity. Mutat. Res., 2012, 733(1-2), 21-33.
[http://dx.doi.org/10.1016/j.mrfmmm.2011.11.003] [PMID: 22093367]
[24]
Ames, B.N. Micronutrient deficiencies. A major cause of DNA damage. Ann. N. Y. Acad. Sci., 1999, 889, 87-106.
[http://dx.doi.org/10.1111/j.1749-6632.1999.tb08727.x] [PMID: 10668486]
[25]
Milić M.; Rozgaj, R.; Kašuba, V.; Oreščanin, V.; Balija, M.; Jukić I. Correlation between folate and vitamin B₁₂ and markers of DNA stability in healthy men: Preliminary results. Acta Biochim. Pol., 2010, 57(3), 339-345.
[http://dx.doi.org/10.18388/abp.2010_2414] [PMID: 20548971]
[26]
Minozzo, R.; Deimling, L.I.; Santos-Mello, R. Cytokinesis-blocked micronucleus cytome and comet assays in peripheral blood lymphocytes of workers exposed to lead considering folate and vitamin B12 status. Mutat. Res., 2010, 697(1-2), 24-32.
[http://dx.doi.org/10.1016/j.mrgentox.2010.01.009] [PMID: 20100595]
[27]
Ni, J.; Liang, Z.; Zhou, T.; Cao, N.; Xia, X.; Wang, X. A decreased micronucleus frequency in human lymphocytes after folate and vitamin B12 intervention: A preliminary study in a Yunnan population. Int. J. Vitam. Nutr. Res., 2012, 82(6), 374-382.
[28]
Misra, U.K.; Kalita, J.; Singh, S.K.; Rahi, S.K. Oxidative stress markers in vitamin B12 deficiency. Mol. Neurobiol., 2017, 54(2), 1278-1284.
[http://dx.doi.org/10.1007/s12035-016-9736-2] [PMID: 26843105]
[29]
Alzoubi, K.; Khabour, O.; Hussain, N.; Al-Azzam, S.; Mhaidat, N. Evaluation of vitamin B12 effects on DNA damage induced by pioglitazone. Mutat. Res., 2012, 748(1-2), 48-51.
[http://dx.doi.org/10.1016/j.mrgentox.2012.06.009] [PMID: 22790087]
[30]
Khabour, O.F.; Alsatari, E.S.; Azab, M.; Alzoubi, K.H.; Sadiq, M.F. Assessment of genotoxicity of waterpipe and cigarette smoking in lymphocytes using the sister-chromatid exchange assay: A comparative study. Environ. Mol. Mutagen., 2011, 52(3), 224-228.
[http://dx.doi.org/10.1002/em.20601] [PMID: 20740646]
[31]
Azab, B.; Alassaf, A.; Abu-Humdan, A.; Dardas, Z.; Almousa, H.; Alsalem, M.; Khabour, O.; Hammad, H.; Saleh, T.; Awidi, A. Genotoxicity of cisplatin and carboplatin in cultured human lymphocytes: A comparative study. Interdiscip. Toxicol., 2019, 12(2), 93-97.
[http://dx.doi.org/10.2478/intox-2019-0011] [PMID: 32206030]
[32]
Mhaidat, N.M.; Alzoubi, K.H.; Khabour, O.F.; Alawneh, K.Z.; Raffee, L.A.; Alsatari, E.S.; Hussein, E.I.; Bani-Hani, K.E. Assessment of genotoxicity of vincristine, vinblastine and vinorelbine in human cultured lymphocytes: A comparative study. Balkan J. Med. Genet., 2016, 19(1), 13-20.
[http://dx.doi.org/10.1515/bjmg-2016-0002] [PMID: 27785403]
[33]
Güner, A. İlhan, S. Cytotoxic, genotoxic, oxidative, and irritant effects of zinc pyrithione in vitro. Toxicol. Environ. Chem., 2020, 102(10), 607-623.
[http://dx.doi.org/10.1080/02772248.2020.1824258]
[34]
Rababa’h, A.M.; Khabour, O.F.; Alzoubi, K.H.; Al-Momani, D.; Ababneh, M. Assessment of genotoxicity of levosimendan in human cultured lymphocytes. Curr. Mol. Pharmacol., 2019, 12(2), 160-165.
[http://dx.doi.org/10.2174/1874467212666190306164926] [PMID: 30848225]
[35]
Al-Khdour, M.S.; Khabour, O.F.; Al-Eitan, L.N.; Alzoubi, K.H. Genotoxicity of nedaplatin in cultured lymphocytes: Modulation by vitamin E. Drug Chem. Toxicol., 2021, 1-5.
[http://dx.doi.org/10.1080/01480545.2021.2015369] [PMID: 34965829]
[36]
Alqudah, M.A.Y.; Al-Ashwal, F.Y.; Alzoubi, K.H.; Alkhatatbeh, M.; Khabour, O. Vitamin E protects human lymphocytes from genotoxicity induced by oxaliplatin. Drug Chem. Toxicol., 2018, 41(3), 281-286.
[http://dx.doi.org/10.1080/01480545.2017.1384835] [PMID: 29092638]
[37]
Jentink, J.; Dolk, H.; Loane, M.A.; Morris, J.K.; Wellesley, D.; Garne, E.; de Jong-van den Berg, L. EUROCAT Antiepileptic Study Working Group. Intrauterine exposure to carbamazepine and specific congenital malformations: Systematic review and case-control study. BMJ, 2010, 341, c6581.
[http://dx.doi.org/10.1136/bmj.c6581] [PMID: 21127116]
[38]
Tomson, T.; Battino, D.; Bonizzoni, E.; Craig, J.; Lindhout, D.; Perucca, E.; Sabers, A.; Thomas, S.V.; Vajda, F. EURAP Study Group. Comparative risk of major congenital malformations with eight different antiepileptic drugs: A prospective cohort study of the EURAP registry. Lancet Neurol., 2018, 17(6), 530-538.
[http://dx.doi.org/10.1016/S1474-4422(18)30107-8] [PMID: 29680205]
[39]
Weston, J.; Bromley, R.; Jackson, C.F.; Adab, N.; Clayton-Smith, J.; Greenhalgh, J.; Hounsome, J.; McKay, A.J.; Tudur Smith, C.; Marson, A.G. Monotherapy treatment of epilepsy in pregnancy: Congenital malformation outcomes in the child. Cochrane Database Syst. Rev., 2016, 11(11), CD010224.
[http://dx.doi.org/10.1002/14651858.CD010224.pub2] [PMID: 27819746]
[40]
Beutler, A.S.; Li, S.; Nicol, R.; Walsh, M.J. Carbamazepine is an inhibitor of histone deacetylases. Life Sci., 2005, 76(26), 3107-3115.
[http://dx.doi.org/10.1016/j.lfs.2005.01.003] [PMID: 15850602]
[41]
Murabe, M.; Yamauchi, J.; Fujiwara, Y.; Miyamoto, Y.; Hiroyama, M.; Sanbe, A.; Tanoue, A. Estimation of the embryotoxic effect of CBZ using an ES cell differentiation system. Biochem. Biophys. Res. Commun., 2007, 356(3), 739-744.
[http://dx.doi.org/10.1016/j.bbrc.2007.03.063] [PMID: 17382902]
[42]
Sinués, B.; Gazulla, J.; Bernal, M.L.; Lanuza, J.; Fanlo, A.; Saenz, M.A.; Barolome, M. Six mutagenicity assays in exposure biomonitoring of patients receiving carbamazepine for epilepsy or trigeminal neuralgia. Mutat. Res., 1995, 334(2), 259-265.
[http://dx.doi.org/10.1016/0165-1161(95)90019-5] [PMID: 7885380]
[43]
Sarikaya, R.; Yüksel, M. Genotoxic assessment of oxcarbazepine and carbamazepine in drosophila wing spot test. Food Chem. Toxicol., 2008, 46(9), 3159-3162.
[44]
Han, Y.; Ma, M.; Li, N.; Hou, R.; Huang, C.; Oda, Y.; Wang, Z. Chlorination, chloramination and ozonation of carbamazepine enhance cytotoxicity and genotoxicity: Multi-endpoint evaluation and identification of its genotoxic transformation products. J. Hazard. Mater., 2018, 342, 679-688.
[http://dx.doi.org/10.1016/j.jhazmat.2017.08.076] [PMID: 28903093]
[45]
Hirsch, A.; Wanounou, M.; Perlman, A.; Hirsh-Raccah, B.; Muszkat, M. The effect of multidrug exposure on neurological manifestations in carbamazepine intoxication: A nested case-control study., 2020, 21(1), 47.
[http://dx.doi.org/10.1186/s40360-020-00425-2]
[46]
Nonaka, S.; Katsube, N.; Chuang, D.M. Lithium protects rat cerebellar granule cells against apoptosis induced by anticonvulsants, phenytoin and carbamazepine. J. Pharmacol. Exp. Ther., 1998, 286(1), 539-547.
[PMID: 9655900]
[47]
Donya, S.M.; Aly, F.A.; Abo-Zeid, M.A. Antigenotoxic efficacy of some vitamins against the mutagenicity induced by ifosfamide in mice. Nat. Sci., 2010, 8(2), 55-66.
[48]
Alzoubi, K.; Khabour, O.; Khader, M.; Mhaidat, N.; Al-Azzam, S. Evaluation of vitamin B12 effects on DNA damage induced by paclitaxel. Drug Chem. Toxicol., 2014, 37(3), 276-280.
[http://dx.doi.org/10.3109/01480545.2013.851686] [PMID: 24215581]
[49]
Waly, M.; Power-Charnitsky, V-A.; Hodgson, N.; Sharma, A.; Audhya, T.; Zhang, Y.; Deth, R. Alternatively spliced methionine synthase in SH-SY5Y neuroblastoma cells: Cobalamin and GSH dependence and inhibitory effects of neurotoxic metals and thimerosal. Oxid. Med. Cell. Longev., 2016, 2016, 6143753.
[http://dx.doi.org/10.1155/2016/6143753]
[50]
Stopper, H.; Treutlein, A.T.; Bahner, U.; Schupp, N.; Schmid, U.; Brink, A.; Perna, A.; Heidland, A. Reduction of the genomic damage level in haemodialysis patients by folic acid and vitamin B12 supplementation. Nephrol. Dial. Transplant., 2008, 23(10), 3272-3279.
[http://dx.doi.org/10.1093/ndt/gfn254] [PMID: 18469307]
[51]
Joksić I.; Leskovac, A.; Petrović S.; Joksić G. Vitamin B12 reduces ribavirin-induced genotoxicity in phytohemaglutinin-stimulated human lymphocytes. Tohoku J. Exp. Med., 2006, 209(4), 347-354.
[http://dx.doi.org/10.1620/tjem.209.347] [PMID: 16864957]
[52]
Majumdar, S.; Mukherjee, S.; Maiti, A.; Karmakar, S.; Das, A.S.; Mukherjee, M.; Nanda, A.; Mitra, C. Folic acid or combination of folic acid and vitamin B(12) prevents short-term arsenic trioxide-induced systemic and mitochondrial dysfunction and DNA damage. Environ. Toxicol. Inter. J., 2009, 24(4), 377-387.
[http://dx.doi.org/10.1002/tox.20442] [PMID: 18825727]

Rights & Permissions Print Cite
Article Metrics
36
2
Wayfinder Image
Open Access Journals Promotions
© 2024 Bentham Science Publishers | Privacy Policy