Evaluation of The Genoprotective Effect of Curcumin Against Methotrexate in Bone Marrow and Spleen Cells in Mice
DOI:
https://doi.org/10.31351/vol32iss3pp134-139Keywords:
Keywords:Curcumin; Methotrexate ; Chromosomal aberrations; miceAbstract
Curcumin is a yellow pigment produced from the rhizomes of the Curcuma longa plant and a primary chemo preventive component of turmeric is used as a spice and food coloring ingredient. Curcumin has a large number of pharmacological activities, such as anticancer, anti-diabetic, antioxidant, anti-infectious, and anti-inflammatory properties.Investigation of the geno-protective effect of curcumin on methotrexate induces chromosomal aberrations of spleen and bone marrow cells. In this study, 32 mice were used and divided into four groups (eight mice at each group) as follows: Group1 (negative control): Dimethyl sulfoxide was given intraperitoneally to mice every day for ten days.Group2 (positive control): Mice were received a single dose (20mg/kg) of methotrexate intraperitoneally Group3: Mice were received (200mg/kg) of curcumin solution intraperitoneally for ten successive days.Group4: Mice were received (200mg/kg) of curcumin solution intraperitoneally for ten successive days and on the day 11, a single dose of methotrexate ( 20 mg/kg ) was injected intraperitoneally . In animals treated with methotrexate, significant elevations of the chromosomal aberrations were observed along with a decline in the mitotic index. Meanwhile, there was a considerable elevation of the mitotic index and no detectable chromosomal changes in the curcumin-supplemented mice. The number of abnormal cells was reduced significantly in the curcumin-treated group in comparison with the methotrexate-treated group. The ability of curcumin to inhibit methotrexate's cytotoxic effects was shown by the compound's ability to raise the mitotic index. According to this finding, curcumin approved to be a protective agent against genotoxic effects of methotrexate.
Keywords: Curcumin, Chromosomal aberrations, Methotrexate, Mitotic index, Mice
References
Gupta SC, Patchva S, Koh W, and Aggarwal BB. Discovery of curcumin a component of golden spice and its miraculous biological activities. Clin. Exp. Pharmacol. Physiol. 2012; 39:283–299.https ://doi. org/10. 1111/ j. 1440-1681.2011.05648.x
Aggarwal BB, Kumar A, and Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res. 2003;23: 363–398.
Kim SR, Park HJ, Bae YH, Ahn SC, Wee HJ, Yun I, Jang HO, Bae MK, and Bae SK. Curcumin down-regulates visfatin expression and inhibits breast cancer cell invasion. Endocrinology. 2012;153:554–563 .doi:10.1210/en.2011-1413.
Wang M, Jiang S, Zhou L, Yu F, Ding H, Li P, Zhou M, Wang K. Potential Mechanisms of Action of Curcumin for Cancer Prevention: Focus on Cellular Signaling Pathways and miRNAs. Int J Biol Sci 2019; 15(6):1200-1214.doi:10.7150/ijbs.33710.
Azuine MA, Bhide SV. Chemopreventive effect of turmeric against stomach and skin tumors induced by chemical carcinogens in Swiss mice. Nutr Cancer. 1992;17(1):77-83. doi:10.1080/01635589209514174.
Kawamori T, Lubet R, Steele VE, et al. Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory agent, during the promotion/progression stages of colon cancer. Cancer Res. 1999;59(3):597-601.
Rao CV, Rivenson A, Simi B, Reddy BS. Chemoprevention of colon carcinogenesis by dietary curcumin, a naturally occurring plant phenolic compound. Cancer Res. 1995; 55(2) :259 -266.
Azuine MA, Kayal JJ, Bhide SV. Protective role of aqueous turmeric extract against mutagenicity of direct-acting carcinogens as well as benzo [alpha] pyrene-induced genotoxicity and carcinogenicity. J Cancer Res Clin Oncol. 1992;118(6):447-452. doi:10. 1007/ BF01629428
Antunes LM, Araújo MC, Darin JD, Bianchi ML. Effects of the antioxidants curcumin and vitamin C on cisplatin-induced clastogenesis in Wistar rat bone marrow cells. Mutat Res. 2000;465(1-2):131-137. doi:10.1016/s1383-5718(99)00220-x.
Thresiamma KC, George J, Kuttan R. Protective effect of curcumin, ellagic acid and bixin on radiation induced genotoxicity. J Exp Clin Cancer Res. 1998;17(4):431-434.
elHamss R, Analla M, Campos-Sanchez J, Alonso-Moraga A, Muñoz-Serrano A, Idaomar M. A dose dependent anti-genotoxic effect of turmeric. Mutat Res. 1999;446(1):135-139. doi:10.1016/s1383-5718(99)00140-0.
Obe G, Pfeiffer P, Savage JR, et al. Chromosomal aberrations: formation, identification and distribution. Mutat Res. 2002;504(1-2):17-36. doi:10.1016/s0027-5107(02)00076-3.
Veronesi U, Bonadonna G and Valagussa P .Lessons from the initial adjuvant cyclophosphamide, methotrexate, and fluorouracil studies in operable breast cancer. J. Clin. Oncol. 2008:26:342–344.
Pellizzer C, Belle E, Adler S, Hartung T and Bremer S .Detection of tissue-specific effects by methotrexate on differentiating mouse embryonic stem cells. Birth Defects Research (Part B), (2004); 71: 331-341.
El –Alfy, N., Mahmoud, M., El-Ashry, S., Alqosaibi, A. (2016). Genotoxic Effect of Methotrexate on Bone Marrow Chromosomes and DNA of Male Albino Mice (Mus musculus). The Egyptian Journal of Hospital Medicine, 64(1), 350-363. doi: 10.12816/0029027
Yurii B. Tsaplev, Viktoria A. Lapina, Aleksei V. Trofimov. Curcumin in dimethyl sulfoxide: Stability, spectral, luminescent and acid-base properties, Dyes and Pigments.2020;177, 108327, ISSN 0143-7208
Padmanabhan S, Tripathi DN, Vikram A, Ramarao P, Jena GB. Methotrexate-induced cytotoxicity and genotoxicity in germ cells of mice: intervention of folic and folinic acid. Mutat Res. 2009; 673(1) :43-52. doi:10 .1016 /j.mrgentox.2008.11.011
Siriviriyakul P, Chingchit T, Klaikeaw N, Chayanupatkul M, Werawatganon D. Effects of curcumin on oxidative stress, inflammation and apoptosis in L-arginine induced acute pancreatitis in mice. Heliyon. 2019; 5(8): e02222.
Preston, RJ, Brian JD and Sheila G Mammalian in vivo cytogenetic assays, Analysis of chromosomal aberrations in mouse bone marrow cells. Mutat. Res. 1987; 189: 157-165.
Mapuskar KA, Anderson CM, Spitz DR, Batinic-Haberle I, Allen BG, E Oberley-Deegan R. Utilizing Superoxide Dismutase Mimetics to Enhance Radiation Therapy Response While Protecting Normal Tissues. Semin Radiat Oncol. 2019;29(1):72-80. doi:10.1016/j.semradonc.2018.10.005.
Spatari G, Fenga C, Minciullo PL, et al. Modification of interleukin-15 serum levels in workers exposed to chemotherapeutic agents. Mediators Inflamm. 2005; (1):60-62. doi:10.1155/MI.2005.60
Rababa'H AM, Alzoubi KH, Khabour OF, Ababneh M. Ameliorative effect of metformin on methotrexate-induced genotoxicity: An in vitro study in human cultured lymphocytes. Biomed Rep. 2021;15(1):59. doi:10.3892/br.2021.1435.
Liu B, Ezeogu L, Zellmer L, Yu B, Xu N, Joshua Liao D. Protecting the normal in order to better kill the cancer. Cancer Med. 2015; 4(9):1394-1403. doi:10.1002/cam4.488.
Martin SA, McCarthy A, Barber LJ, et al. Methotrexate induces oxidative DNA damage and is selectively lethal to tumour cells with defects in the DNA mismatch repair gene MSH2. EMBO Mol Med. 2009; 1(6-7):323-337. doi:10.1002/emmm.200900040.
El –Alfy, N., Mahmoud, M., El-Ashry, S., Alqosaibi, A. (2016). 'Genotoxic Effect of Methotrexate on Bone Marrow Chromosomes and DNA of Male Albino Mice (Mus musculus)', The Egyptian Journal of Hospital Medicine, 64(1), pp. 350-363. doi: 10. 12816/ 0029027.
Giordano A, Tommonaro G. Curcumin and Cancer. Nutrients. 2019; 11(10):2376. Published 2019 Oct 5. doi:10.3390 /nu11102376
Mansouri K, Rasoulpoor S, Daneshkhah A, et al. Clinical effects of curcumin in enhancing cancer therapy: A systematic review. BMC Cancer. 2020; 20(1):791. Published 2020 Aug 24. doi:10.1186/s12885-020-07256-8
Prasad S, Gupta SC, Tyagi AK, Aggarwal BB. Curcumin, a component of golden spice: from bedside to bench and back. Biotechnol Adv. 2014; 32(6):1053-1064. doi:10. 1016 /j. biotechadv. 2014.04.004 .
Schneider C, Gordon ON, Edwards RL, Luis PB. Degradation of Curcumin: From Mechanism to Biological Implications. J Agric Food Chem. 2015; 63(35):7606-7614. doi: 10. 1021/acs.jafc.5b00244
El-Ashmawy IM, Ashry KM, El-Nahas AF, Salama OM. Protection by turmeric and myrrh against liver oxidative damage and genotoxicity induced by lead acetate in mice. Basic Clin PharmacolToxicol. 2006;98(1):32-37. doi: 10. 1111 /j.1742-7843.2006.pto_228.x
Kalpana C, Menon VP. Inhibition of nicotine-induced toxicity by curcumin and curcumin analog: a comparative study. J Med Food. 2004; 7(4):467-471. doi:10. 1089/ jmf. 2004. 7.467.
Thresiamma KC, George J, Kuttan R. Protective effect of curcumin, ellagic acid and bixin on radiation induced genotoxicity. J Exp Clin Cancer Res. 1998; 17(4):431-434.
Acar, A., Singh, D. & Srivastava, A.K. Assessment of the ameliorative effect of curcumin on pendimethalin-induced genetic and biochemical toxicity. Sci Rep 12, 2195 (2022). https://doi.org/10.1038/s41598-022-06278-5
Pujol-Canadell M, Puig R, Armengol G, Barrios L, Barquinero JF. Chromosomal aberration dynamics through the cell cycle. DNA Repair (Amst). 2020;89: 102838. doi:10.1016/j.dnarep.2020.102838
Barbi G, Steinbach P, Vogel W. Nonrandom distribution of methotrexate-induced aberrations on human chromosomes. Detection of further folic acid sensitive fragile sites. Hum Genet. 1984; 68(4):290-294. doi:10 .1007/ BF00292586.
Downloads
Published
Issue
Section
License
Copyright (c) 2023 Iraqi Journal of Pharmaceutical Sciences( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512)
This work is licensed under a Creative Commons Attribution 4.0 International License.
