Antimutagenic effects of copaiba oils (Copaifera langsdorffii Desf.) and flaxseed (Linum usitatissimum L.) against the clastogen – cyclophosphamide, in Wistar rat
Keywords:Medicinal plants; Functional food; Cytotoxicity; Chromosomal alteration.
Copaiba oil extracted from the trunk of Copaifera langsdorffii Desf. and flaxseed oil extracted from the seeds of Linum usitatissimum L., are widely used for the prevention and treatment of many diseases, including cancer. The aim of this study was to assess the antimutagenic effect of these oils against the damage-inducing agent cyclophosphamide, in Rattus norvegicus treated in vivo, by gavage, using cytotoxicity and chromosomal alteration test. The animals were submitted to a single dose of copaiba oil and of flaxseed oil in the simultaneous treatment, pre-treatment and pos-treatment for 24 hours. None of these treatments presented cytotoxic effect. Treatments both oils and cyclophosphamide have significantly reduced the chromosomal damage caused by the clastogen. In groups treated with copaiba oil the reduction percentage was 77% for the simultaneous treatment, 83% for the pre-treatment and 75% for the pos-treatment, whereas in those treated with flaxseed oil was 94% for the pre-treatment and 96% for the simultaneous and pos-treatment. These results indicate that the both oils are not mutagenic, in contrast, they present antimutagenic activity against this clastogenic agent, which represents a protective effect on the cells against the drug that has damaged the genetic material.
Álvarez-González, E., Madrigal-Bujaidar, S., & Castro-García (2014). Antigenotoxic capacity of beta-caryophyllene in mouse, and evaluation of its antioxidant and GST induction activities. J Toxicol Sci, 39, 849-859.
Arruda, C., Mejía, J. A. A., Ribeiro, V. P., Borges, C. H. G., Martins, C. H. G., Veneziani R. C. S., Ambrósio, S. R., & Bastos, J. K. (2019). Occurrence, chemical composition, biological activities and analytical methods on Copaifera genus—a review. Biomed Pharmacother, 109, 1-20.
AVMA Guidelines for the Euthanasia of Animals, 2007. 2007 ed. American Veterinary Medical Association.
Azevedo, L., de Araujo Ribeiro, P. F., de Carvalho Oliveira, J. A., Correia, M. G., Ramos, F. M., de Oliveira, E. B., & Stringheta, P. C. (2019). Camu-camu (Myrciaria dubia) from commercial cultivation has higher levels of bioactive compounds than native cultivation (Amazon Forest) and presents antimutagenic effects in vivo. J Science Food Agric, 99 (2), 624-631.
Becker, G., Brusco, I., Casoti, R., Marchiori, M. C. L., Cruz, L., Trevisan, G., & Oliveira, S. M. (2020). Copaiba oleoresin has topical antinociceptive activity in a UVB radiation-induced skin-burn model in mice. J Ethnopharmacol, 250 (25), 112476.
Bernacchia, R., Preti, R., & Vinci, G. (2014). Chemical Composition and Health Benefits of Flaxseed. J Nutr Food Sci, 2, 1-9.
Berquin, I. M., Edwards, I. J., & Chen, Y. Q. (2008). Multi-targeted therapy of cancer by omega-3 fatty acids. Cancer Lett, 269, 363-377.
Bhatia, A. L., Manda, K., Patni, S., & Sharma, A. L. (2006). Prophylactic action of linseed (Linum usitatissimum) oil against cyclophosphamide-induced oxidative stress in mouse brain. J Med Food, 9, 261-264.
Carvalho, J. C., Cascon, V., Psebon, L. S., Morimoto, M. S., Cardoso, L. G., Kaplan, M. A., & Gilbert, B. (2005). Topical antiinflammatory and analgesic activities of Copaifera duckei dwyer. Phytother Res, 19, 946-950.
Cunnane, S. C., Ganguli, S., Menard, C., Liede, A. C., Hamadeh, M. J., Chen, Z., Wolever, T. M. S., & Jenkins, D. J. A. (1993). High α-linolenic acid flaxseed (Linum usitatissimum): some nutritional properties in humans. Br J Nutr, 69, 443-453.
De Flora, S., & Ramel, C. (1998). Mechanisms of inhibitors of mutagenesis and carcinogenesis. Classification and overview. Mutat Res Mol M, 2002, 285-306.
Di Sotto, A., Mancinelli, R., Gullì, M., Eufemi, M., Mammola, C. L., Mazzanti, G., & Di Giacomo, S. (2020). Chemopreventive Potential of Caryophyllane Sesquiterpenes: An Overview of Preliminary Evidence. Cancers, 18,12 (10), 3034.
Di Sotto, A., Mazzanti, G., Carbone, F., Hrelia, P., & Maffei, F. (2010). Inhibition by β-caryophyllene of ethyl methanesulfonate-induced clastogenicity in cultured human lymphocytes. Mutat Res, 699, 23-28.
Dugani, A., Auzzi, A., Naas, F., & Megwez, S. (2008). Effects of the Oil and Mucilage from Flaxseed (Linum usitatissimum) on Gastric Lesions Induced by Ethanol in Rats. Libyan J Med, 3, 166-169.
Durnev, A. D. (2018). Antimutagenesis and Antimutagens. Hum Physiol, 44, 336-355.
Ezzat, S. M., Shouman, S. A., Elkhoely, A., Attia, Y. M., Elsesy, M. S., El Senousy, A. S., Choucry, M. A., El Gayed, S. H., El Sayed, A. A., Sattar, E. A., & El Tanbouly, N. (2018). Anticancer potentiality of lignan rich fraction of six flaxseed cultivars. Sci Rep, 8 (544), 10.1038/s41598-017-18944-0.
Ferguson, L. R., Philpott, M., & Karuanasinghe, N. (2004). Dietary cancer and prevention using antimutagens. Toxicology,198, 147-159.
Ford, C. E., & Hamerton, J. L. (1956). A colchicine, hypotonic citrate, squash sequence for mammalian chromosome. Stain Technol, 3, 247-251.
Gelmini, F., Beretta, G., Anselmi, C., Centini, M., Magni, P., Ruscica, M., Cavalchini, A., & Facino, R. M. (2013). GC–MS proﬁling of the phytochemical constituents of the oleoresin from Copaifera langsdorfﬁi Desf. and a preliminary in vivo evaluation of its antipsoriatic effect. Int J Pharm, 440, 170-178.
Gomes, N. M., Rezende, C. M., Fontes, S. P., Matheus, M. E., & Fernandes, P.D (2007). Antinociceptive activity of Amazonian Copaiba oils. J Ethnopharmacol,109, 486-492.
Gomes-Carneiro, M. R., Dias, D. M. M., De-Oliveira, A. C. A. X., & Paumgartten, F. J. R. (2005). Evaluation of mutagenic and antimutagenic activities of α-bisabolol in the Salmonella/ microsome assay. Mutat Res, 585, 105-112.
Guide for the Care and Use of Laboratory Animals, 2011, eightn ed. The National Academies Press, Washington.
Hamedi, A., Bayat, M., Asemani, Y., & Amirghofran, Z. (2022). A review of potential anti-cancer properties of some selected medicinal plants grown in Iran. J Herb Med, 33, 100557.
Kobayashi, C., Fontanive, T. O., Enzweiler, B. G., de Bona, L. R., Massoni, T., Apel, M. A., Henriques, A. T., Richter, M. F., Ardenghi, P., & Suyenaga, E. S. (2011). Pharmacological evaluation of Copaifera multijuga oil in rats. Pharm Biol, 49, 306-13.
Kok, T. M., Van Breda, S. G., & Manson, M. M. (2008). Mechanisms of combined action of different chemopreventive dietary compounds. Eur J Clin Nutr, 47, 51-59.
Koklesova, L., Liskova, A., Samec, M., Qaradakhi, T., Zulli, A., Smejka,l K., Kajo, K., Jakubikova, J., Behzadi, P., Pec, M., et al. (2020). Genoprotective activities of plant natural substances in cancer and chemopreventive strategies in the context of 3P medicine. EPMA J, 11, 261-287.
Leandro, L. M., Vargas, F. S., Barbosa, P. C. S., Neves, J. K. O., Silva, J. A., & Veiga-Junior, V. F. (2012). Chemistry and Biological Activities of Terpenoids from Copaiba (Copaifera spp.) Oleoresins. Molecules, 17, 3866-3889.
Leite-Legatti, A. V., Batista, A. G., Dragano, N. R. V., Marques, A. C., Malta, L. G., Riccio, M. F., et al. (2012). Marostica Jaboticaba peel: Antioxidant compounds, antiproliferative and antimutagenic activities. Food Res Inter, 49 (1), 596-603.
Maistro, E. L., Carvalho, J. C. T., Cascon, V., & Kaplan, M. A. C. (2005). In vivo evaluation of the mutagenic potential and phytochemical characterization of oleoresin from Copaifera duckei Dwyer. Genet Mol Biol, 28, 833-838.
Majolo, F., Delwing, L. K. O. B., Marmitt, D. J., Bustamante-Filho, I. C., & Goettert, M. I. (2019). Medicinal plants and bioactive natural compounds for cancer treatment: Important advances for drug Discovery. Phytochem Lett, 31, 196-207.
Malik, S., Kaur, K., Prasad, S., Jha, N. K., & Kumar, V. (2021). A perspective review on medicinal plant resources for their antimutagenic potentials. Environ Sci Pollut Res, 24, s11356-021-16057-w.
Mason, J. K., Chen, J., & Thompson, L. U. (2010). Flaxseed oil–trastuzumab interaction in breast cancer. Food Chem Toxicol, 48, 2223–2226.
Meeran, S. M., & Katiyar, S. K. (2008). Cell cycle control as a basis for cancer chemoprevention through dietary agents. Front Biosci, 13, 2191-2202.
Menezes, A. C. dos S., Alves, L. D. B., Goldemberg, D. C., Melo, A. C. de, & Antunes, H. S. (2022). Anti-inflammatory and wound healing effect of Copaiba oleoresin on the oral cavity: A systematic review. Heliyon, 8 (2), e08993.
Oomah, B. D. (2001). Flaxseed as a functional food source. J Sci Food Agric, 81, 889-894.
Paiva, L. A. F., Gurgel, L. A., De-Sousa, E. T., Silveira, E. R., Silva, R. M., Santos, F. A., & Rao, V. S. N. (2204). Protective effect of Copaifera langsdorffii oleo-resin against acetic acid-induced colitis in rats. J Ethnopharmacol , 93, 51-56.
Pal, M., & Ghosh, M. (2012). Prophylactic effect of a-linolenic acid and a-eleostearic acid against MeHg induced oxidative stress, DNA damage and structural changes in RBC membrane. Food Chem Toxicol, 50, 2811-2818.
Parikh, M., Netticadan, T., & Pierce, G. N. (2018). Flaxseed: its bioactive components and their cardiovascular benefits. Am J Physiol, 314 (2), H146-H159.
Park, E. J., & Pezzuto, J. M. (2002). Botanicals in cancer chemoprevention. Cancer Metast Rev, 21, 231-255.
Pasquel-Reátegui, J. L., Santos, L. C. dos, Barrales, F. M., Grober, V. L., Soares Forte, M. B., Sartoratto, A.Queiroga, C. L., & Martínez, J. (2022). Fractionation of sesquiterpenes and diterpenic acids from copaiba (Copaifera officinalis) oleoresin using supercritical adsorption. J Supercrit Fluids, 184, 105565.
Pei, S., Alan, H., & Wang, Y. (2020). Vital roles for ethnobotany in conservation and sustainable development. Plant Divers, 42, 399-400.
Roynette, C. E., Calderb, P. C., Dupertuisa, Y. M., & Pichard, C. (2004). n-3 polyunsaturated fatty acids and colon prevention. Clin Nutr, 23, 139-151.
Santos Junior, H. M., Oliveira, D. F., de Carvalho, D. A., Pinto, J. M., Campos, V. A., Mourão, A. R., Pessoa, C., de Moraes, M. O., & Costa-Lotufo, L. V. (2010). Evaluation of native and exotic Brazilian plants for anticancer activity. J Nat Med, 64, 231-238.
Santos, M. de O., Camilo, C. J., Macedo, J. G. F., de Lacerda, M. N. S., Lopes, C. M. U., Rodrigues, A. Y. F., da Costa, J. G. M., & Souza, M. M. de A., (2022). Copaifera langsdorffii Desf.: A chemical and pharmacological review. Biocatal Agric Biotechnol, 39, 102262.
Sarpietro, M. G., Di Sotto, A., Accolla, M. L., & Castelli, F. (2015). Differential Scanning Calorimetry Study on the Interaction of β-Caryophyllene and β-Caryophyllene Oxide with Phospholipid Bilayers. Thermochim Acta, 600, 28-34.
Toboutia, P. L., Martins, T. C. de A., Pereira, T. J., & Mussi, M. C. M. (2017). Antimicrobial activity of copaiba oil: A review and a call for further research. Biomed Pharmacother, 94, 93-99.
Toure, A., & Xu, X. M. (2010). Flaxseed lignans: source, biosynthesis, metabolism, antioxidant activity, bio-active components, and health benefits. Compr Rev Food Sci F, 9 (3), 261-269.
Trentin, G. A., Moody, J., Torous, D. K., Thompson, L. U., & Heddle, J.A. (2004). The influence of dietary flaxssed and other grains, fruits and vegetables on the frequency of spontaneous chromosomal damage in mice. Mutat Res, 551, 213-222.
Tülüce, Y., Özkol, H., & Koyuncu, I. (2012). Photoprotective effect of flax seed oil (Linum usitatissimum L.) against ultraviolet C-induced apoptosis and oxidative stress in rats. Toxicol Ind Health, 28(2), 99-107.
Veiga Junior, V. F., & Pinto, A. (2002). O gênero Copaifera L. Quim Nova, 25, 273-286.
Wang , H., Wang, J., Qiu , C., Ye, Y., Guo , X., Chen, G., Li, T., Wang, Y., Fu, X., & Liu, R. H. (2017). Comparison of phytochemical profiles and health benefits in fiber and oil flaxseeds (Linum usitatissimum L.). Food Chem, 1(214), 227-233.
Weiler, H. A., Kovacs, H., Nitschmann, E., Bankovic-Calic, N., Aukema, H., & Ogborn, M. (2007). Feeding flaxseed oil but not secoisolariciresinol diglucoside results in higher bone mass in healthy rats and rats with kidney diseases. Prostaglandins Leukot Essent Fat Acids, 76, 269-275.
Weisburger, J. H. (2001). Antimutagenesis and anticarcinogenesis, from the past to the future. Mutat Res Mol M, 480-481, 23-35.
Williams, D., Verghese, M., Walker, L. T., Boateng, J., Shackelford, L., & Chawan, C. B. (2007). Flax seed oil and flax seed meal reduce the formation of aberrant crypt foci (ACF) in azoxymethane - induced colon cancer in Fisher 344 male rats. Food Chem Toxicol, 45, 153-159.
Wong, A. H. C., Gottesman, I. I., & Petronis, A. (2005). Phenotypic differences in genetically identical organisms: the epigenetic perspective. Hum Mol Genet, 14, 14-18.
How to Cite
Copyright (c) 2022 Michele Cristina Heck; Mariana Yoshimoto-Higaki; Mariane Aparecida Franco de Godoy; Debora Elisa Antunes de Mendonça; Veronica Elisa Pimenta Vicentini
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.