Versions
- 2021-05-23 (2)
- 2021-03-08 (1)
Keywords
How to Cite
Abstract
Homeopathic medicines comprise the use of pharmacotechnical processes that promote successive dilutions, followed by grinding or agitation of compounds. The purpose of this study was to assess the genotoxic potential of ultra-diluted cyclophosphamide (CF) and nux vomica associated with or without allopathic CF in Swiss Webster mice, using the micronucleus test. The compounds were prepared according to the Brazilian homeopathic pharmacopoeia. Swiss Webster mice were randomly divided into eight groups (n=6) according to the compounds to be tested and received by gavage (vehicle or CF) or by oral mucosa contact (ultra-diluted CF and nux vomica, and dynamized solutions) once a day for 7 days. After this, one of the groups treated with the dynamized compound was challenged by the administration of the allopathic CF. The dynamized ultra-diluted nux vomica and CF compounds showed lower white cell counts in mice. However, no compound was able to mitigate the genotoxic effects of CF in micronucleus assay. The dynamized compounds did not cause damage to the spleen and thymus, and when used intraperitoneally, they were able to mitigate the effect of CF on thymic cortical reduction in mice. Further studies with nux vomica and dynamized CF should be performed to better delineate their possible therapeutic potential in reducing adverse effects on chemotherapy.
References
Agência Nacional de Vigilância Sanitária - ANVISA. (2007). Resolução da Diretoria Colegiada - RDC n° 26, March 30, 2007. http://antigo.anvisa.gov.br/legislacao#/visualizar/27963
Agência Nacional de Vigilância Sanitária – ANVISA. (2011). Brazilian Homeopathic Pharmacopoeia (3rd ed., ANVISA e OPAS, trad.). https://www.gov.br/anvisa/pt-br/assuntos/farmacopeia/farmacopeia-homeopatica/ arquivos/8056json-file-1
Almeida, V. L., Leitão, A., Reina, L. C. B., Montanari, C. A., Donnici, C. L., & Lopes, M. T. P. (2005). Câncer e agentes antineoplásicos ciclo-celular específicos e ciclo-celular não específicos que interagem com o DNA: uma introdução. Quimica Nova, 28(1), 118-129. http://dx.doi.org/10.1590/S0100-40422005000100021.
Amaral, J. G., Cardoso, T. N., Carvalho, A. C., Coelho, C. P., Waisse, S., Perez, E. C., & Bonamin, L. V. (2018). High-diluted thymulin on Ehrlich tumor growth in mice and the importance of tumor microenvironment. International Journal of High Dilution Research, 17(3-4), 20-41.
Banerjee, P., Biswas, S. J., Belon, P., & Khuda-Bukhsh, A. R. (2007). A potentized homeopathic drug, Arsenicum Album 200, can ameliorate genotoxicity induced by repeated injections of arsenic trioxide in mice. Journal of Veterinary Medicine. A, Physiology, Pathology, Clinical Medicine, 54(7), 370-376. http://dx.doi.org/10.1111/j.1439- 0442.2007.00945.x. PMid:17718811.
Barbour, E. K., Sagherian, V., Talhouk, S., Talhouk, R., Farran, M. T., Sleiman, F. T., & Harakeh, S. (2004). Evaluation of homeopathy in broiler chickens exposed to live viral vaccines and administered Calendula officinalis extract. Medical Science Monitor, 10(8), BR281-BR285. PMid:15277989.
Biswas, S. J., & Khuda-Bukhsh, A. R. (2002). Effect of a homeopathic drug, Chelidonium, in amelioration of p-DAB induced hepatocarcinogenesis in mice. BMC Complementary and Alternative Medicine. http://www. biomedcentral.com/1472-6882/2/4
Biswas, S. J., Pathak, S., Bhattacharjee, N., Das, J. K., & Khuda-Bukhsh, A. R. (2005). Efficacy of the potentized homeopathic drug, Carcinosin 200, fed alone and in combination with another drug, Chelidonium 200, in amelioration of p-dimethylaminoazobenzene-induced hepatocarcinogenesis in mice. The Journal of Alternative and Complementary. Medicine, 11(5), 839-854. PMid:16296917.
Blankenberg, F. G., Naumovski, L., Tait, J. F., Post, A. M., & Strauss, H. W. (2001). Imaging cyclophosphamide-induced intramedullary apoptosis in rats using 99mTc-radiolabeled annexin V. Journal of Nuclear Medicine, 42(2), 309-316. PMid:11216531.
Bonassa, E. M. A., & Santana, T. R. (2005) Enfermagem em Terapêutica Oncológica. 3.ed. São Paulo: Atheneu.
Borges, R. E., Santos, L. R. S., Benvindo-Souza, M., Modesto, R. S., Assis, R. A., & de Oliveira, C. (2019). Genotoxic evaluation in tadpoles associated with agriculture in the Central Cerrado, Brazil. Archives of Environmental Contamination and Toxicology, 77(1), 22-28. http://dx.doi.org/10.1007/s00244-019-00623-y. PMid:30949743
Bruni, E., Cazzetta V, Donadon M, Cimino M, Torzilli G, Spata G, Leonardi G, Dieli F, Mikulak J, Mavilio D. (2019). Chemotherapy accelerates immune-senescence and functional impairments of Vδ2pos T cells in elderly patients affected by liver metastatic colorectal cancer. Journal for Immunotherapy of Cancer, 7(1):347.
Buchi, F., & Del Vecchio, M. (2002). Qualidade de vida para pacientes com câncer e AIDS. Mita´y, 1, 33-38.
Choy, W. N. (2001). Regulatory Genetic toxicology tests. Editors genetic toxicology and cancer risk assessment. (pp. 93-113). Marcel Dekker.
Dantas, F. (2004). Homeopatia na universidade: educação, assistência e pesquisa. Universia.
Eldahshan, O. A., & Abdel-Daim, M. M. (2015). Phytochemical study, cytotoxic, analgesic, antipyretic and anti-inflammatory activities of Strychnos nux-vomica. Cytotechnology, 67(5), 831-844. http://dx.doi.org/10.1007/ s10616-014-9723-2. PMid:24711053.
Fenech, M. (2005). In vitro micronucleus technique to predict chemosensitivity. Methods in Molecular Medicine, 111, 3-32. http://dx.doi.org/10.1385/1-59259-889-7:003. PMid:15911968.
Ferreira, S. G. (2008). Estudo dos efeitos da melatonina sobre os danos ao DNA induzido pela ciclofosfamida em ratos Wistar pinealectomizado [Tese de doutorado, Universidade de São Paulo, Instituto de Ciências Biomédicas]. http://dx.doi.org/10.11606/T.42.2008.tde-15092008-131230.
Fry, M. M., & McGavin, M. D. (2007). Bone marrow, blood cells, and lymphatic system. Pathologic Basis of Veterinary Disease (4th ed.). Mosby Elsevier.
Garas, G., Crawford, G. P., & Cain, M. (1995). Anaphylactic reaction to intravenous cyclophosphamide. Australian and New Zealand Journal of Medicine, 25(1), 59. http://dx.doi.org/10.1111/j.1445-5994.1995.tb00585.x. PMid:7786253.
Garcia, M., Sertório, S. P., Alves, G. J., Chate, S. C., Carneiro, R., & Lallo, M. A. (2004). Uso da ciclofosfamida em modelo de imunodepressão experimental em ovinos. Pesquisa Veterinária Brasileira, 24(3), 115-119. http:// dx.doi.org/10.1590/S0100-736X2004000300001.
Green, R. M., Schapel, G. J., & Sage, R. E. (1989). Cutaneous vasculitis due to cyclophosphamide therapy for chronic lymphocytic leukemia. Australian and New Zealand Journal of Medicine, 19(1), 55-57. http://dx.doi. org/10.1111/j.1445-5994.1989.tb01677.x. PMid:2764806.
Guo, R., Wang, T., Zhou, G., Xu, M., Yu, X., Zhang, X., Sui, F., Li, C., Tang, L., & Wang, Z. (2018). Botany, Phytochemistry, Pharmacology and Toxicity of Strychnos nux-vomica L.: A Review. The American Journal of Chinese Medicine, 46(1), 1-23. http://dx.doi.org/10.1142/S0192415X18500015. PMid:29298518.
Gupta, H. R., Patil, Y., Singh, D., & Thakur, M. (2016). Embryonic Zebrafish Model - A Well-Established Method for Rapidly Assessing the Toxicity of Homeopathic Drugs: - Toxicity Evaluation of Homeopathic Drugs Using Zebrafish Embryo Model. Journal of Pharmacopuncture, 19(4), 319-328. http://dx.doi.org/10.3831/ KPI.2016.19.033. PMid:28127503.
Hosseinimehr, S. J., & Karami, M. (2005). Chemoprotective effects of captopril against cyclophosphamide-induced genotoxicity in mouse bone marrow cells. Archives of Toxicology, 79(8), 482-486. http://dx.doi.org/10.1007/ s00204-005-0655-7. PMid:15856182.
Hussain, B., Fatima, M., Al-Ghanim, K. A., Al-Misned, F., & Mahboob, S. (2020). Assessment of DNA integrity through MN bioassay of erythrocytes and histopathological changes in Wallago attu and Cirrhinus mirigala in response to freshwater pollution. Saudi Journal of Biological Sciences, 27(1), 251-260. http://dx.doi.org/10.1016/j. sjbs.2019.09.003. PMid:31889845.
Hussain, B., Sultana, T., Sultana, S., Masoud, M. S., Ahmed, Z., & Mahboob, S. (2018). Fish eco-genotoxicology: Comet and micronucleus assay in fish erythrocytes as in situ biomarker of freshwater pollution. Saudi Journal of Biological Sciences, 25(2), 393-398.
Instituto Nacional do Câncer – INCA. (2015). Homeopathic medicines for adverse effects of cancer treatments.. http.//www.inca.gov.br
Kassab, S., Cummings, M., Berkovitz, S., van Haselen, R., & Fisher, P. (2009). Homeopathic medicines for adverse effects of cancer treatments. The Cochrane Database of Systematic Reviews, 15(2), CD004845. http://dx.doi. org/10.1002/14651858.CD004845.pub2. PMid:19370613.
Khayyat, L., Essawy, A., Sorour, J., & Soffar, A. (2017). Tartrazine induces structural and functional aberrations and genotoxic effects in vivo. PeerJ. 23(5), e3041.
Khuda-Bukhsh, A. R. (2009). Mice as a model for homeopathy research. Homeopathy, 98(4), 267-279.
Knysak, D. J., Mclean, J. A., Solomon, W. R., Fox, D. A., & Joseph Mccune, W. (1994). Immediate hypersensitivity reaction to cyclophosphamide. Arthritis and Rheumatism, 37(7), 1101-1104. http://dx.doi.org/10.1002/ art.1780370717. PMid:8024619.
MacGregor, J. T., Heddle, J. A., Hite, M., Margolin, B. H., Ramel, C., Salamone, M. F., Tice, R. R., & Wild, D. (1987). Guidelines for the conduct of micronucleus assays in mammalian bone marrow erythrocytes. Mutation Research, 189(2), 103-112.
Murti, L., & Horsman, L. R. (1979). Acute hypersensitivity reaction to cyclophosphamide. The Journal of Pediatrics, 94(5), 844-845. http://dx.doi.org/10.1016/S0022-3476(79)80178-X. PMid:448505.
Nascimento, H. F. S., Cardoso, P. C. D. S., Ribeiro, H. F., Mota, T. C., Gomes, L. M., Khayat, A. S., Guimarães, A. C., Amorim, M. I. M., Burbano, R. R., & Bahia, M. O. (2016). In vitro assessment of anticytotoxic and antigenotoxic effects of CANOVA. Homeopathy. 105(3):265-269.
Norppa, H., & Falck, G. C. M. (2003). What human micronuclei contain? Mutagenesis, 18(3), 221-233. PMid:12714687.
Organisation for Economic Cooperation and Development – OECD. (1997). OECD guideline for the testing of chemicals- mammalian erythrocyte micronucleous test (No. 474). OECD.
Pinto, L. F. (1995). Homeopatia veterinária (87 p.). Rio de Janeiro: UFRRJ.
Pinto, L. F. (2008a). Publicações em homeopatia – problemas e soluções. The British Homoeopathic Journal, 10(1), 22-29.
Pinto, L. F. (2008b). Homeopathic veterinary clinical protocol. In L. V. Bonamin (Ed.), Signals and Images II: Contributions and Contradictions about High Dilution Research. Springer. http://dx.doi.org/10.1007/978-1-4020-8535-2_12.
Pinto, L. F. (2009). Homeopathy at veterinary school – teaching, research and clinical care. The British Homoeopathic Journal, 11(2), 20-23.
Piraíno, R. (2003). Canova - vida com qualidade. http://www.metodocanova.com.br
Pitari, G. (2007). Scientific research in homeopathic medicine: validation methodology and perspectives. Evidence-Based Complementary and Alternative Medicine, 4(2), 271-273. http://dx.doi.org/10.1093/ecam/nel085.
Piveta, L. A. (2005). Efeitos tóxicos do etanol e sua relação com o estresse oxidativo [Dissertação de mestrado, Universidade Federal de Santa Maria, Programa de Pós-gradução em Ciências Biológicas – Bioquímica Toxicológica]. Repositório Institucional UFSM. https://repositorio.ufsm.br/handle/1/11078
Posadzki, P., & Ernst, E. (2013). Adverse effects of homeopathy: A systematic review of published case reports and case series. International Journal of Clinical Practice, 67(4), 389. http://dx.doi.org/10.1111/ijcp.12140. PMid:23521336.
Preethi, K. C., Nair, C. K., & Kuttan, R. (2008). Clastogenic potential of Ruta graveolens extract and a homeopathic preparation in mouse bone marrow cells. Asian Pacific Journal of Cancer Prevention, 9(4), 763-769. PMid:19256773.
Rosas, E. (2006). Avaliação dos ensaios clínicos homeopáticos na área das doenças infecciosas e parasitárias [Dissertação de mestrado, Universidade Federal da Bahia, Faculdade de Medicina da Bahia, Programa de Pós-graduação em Medicina e Saúde]. Dpub. http://www.ihb.hospedagemdesites.ws/dpub/editoraDissertacoes.asp
Schmid, W. (1976). The micronucleus test for cytogenetic analysis. In A. Hollaender (Ed.), Chemical Mutagens Principies and Methods for their Detection (Vol. 5, pp. 31-53). Plenum Press. http://dx.doi.org/10.1007/978-1-4684-0892-8_2.
Schuurman, H. J., Smith, H. T., & Cozzi, E. (2005). Tolerability of cyclosphosphamide and methotrexate induction immunosuppression in nonhuman primates. Toxicology, 213(1-2), 1-12.
Seligmann, I. C., Lima, P. D., Cardoso, P. C., Khayat, A. S., Bahia, M. O., Buchi, DDE. F., Cabral, I. R., & Burbano, R. R. (2003). The anticancer homeopathic composite “Canova Method” is not genotoxic for human lymphocytes in vitro. Genetics and Molecular Research: GMR, 2(2), 223-228. PMid:14966688.
World Health Organization – WHO. (2009). Safety issues in the preparation of homeopathic medicines (448 p.) WHO.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2021 Juliana da Silva Coelho, Manuella Espindola Vieira, Alaide dos Santos Rodrigues, Luiz Figueira Pinto, Isabel Cristina Fábregas Bonna, Kelly Cristina Demarque, Maria Alice Amaral Kuzel