Evaluación de la citotoxicidad, genotoxicidad y toxicidad subcrónica de diésteres p-metoxicinámicos extraídos de Copernicia prunifera (Miller) H. E. Moore en modelo experimental
DOI:
https://doi.org/10.33448/rsd-v9i8.6251Keywords:
Carnauba wax; P-methoxycinnamic diesters; Subchronic oral toxicity; Micronuclei.Abstract
P-methoxycinnamic diesters from carnauba wax powder (PCO - C) – cinnamic acid derivate – have been associated with new properties such as hypolipidemic, hypocholesterolemic and hypoglycaemic effects in mice. The present study aimed to investigate the safety profile of PCO - C by evaluating the subchronic oral toxicity, genotoxicity and mutagenicity using in vivo experimental models. Therefore, for the present research, characterized as experimental and of a quantitative nature, 80 Swiss mice, of both genders, were used for the analysis of mutagenicity, genotoxicity, analysis of the biochemical, hematological and toxicological profiles. PCO - C did not induce changes in the mass of animals besides not interfering in blood parameters. PCO - C showed no hemolysis of mouse erythrocytes. PCO - C caused no mutagenic or genotoxic effects in male and female mice treated with 500 mg/Kg/day during 90 days. In addition, PCO - C did not change some important serum parameters (alanine aminotransferase, aspartate aminotransferase, total cholesterol and creatinine), hematological profile, structural arrangement of the kidneys, heart, stomach and spleen. The results demonstrate that PCO - C is not genotoxic, and did not present toxicity when used orally for up to 90 days. Overall, the study has demonstrated the safety of PCO - C for potential uses in biomedical areas.
References
Albuquerque, U. P., Medeiros, P. M., de Almeida, A. L. S., Monteiro, J. M., de Freitas Lins Neto, E. M., de Melo, J. G., & dos Santos, J. P. (2007). Medicinal plants of the caatinga (semi-arid) vegetation of NE Brazil: A quantitative approach. Journal of Ethnopharmacology, 114 (1), 325–354.
Ayres, M. C. C., Brandão, M. S., Vieira-Júnior, G. M., Menor, J. C. A. S., Silva, H. B., Soares, M. J. S., & Chaves, M. H. (2018). Atividade antibacteriana de plantas úteis e constituintes químicos da raiz de Copernicia prunifera. Revista Brasileira de Farmacognosia, 18 (3), 35-39.
European Food Safety Authority. (2012). Scientific Opinion on the re-evaluation of carnauba wax (E 903) as a food additive EFSA Journal, 10 (2012), 10.2903/j.efsa.2012.2880
FDA. Food and Drugs Chapter 9 - federal food, drug, and cosmetic act, Subchapter II - Definitions, Sec. 321 – Definitions; generally, Code of Federal Regulations, Titel 21, Sec. 321 § (1983). https://doi.org/CFR.
Filho, A. C. V., Rodrigues, P. A. S., Benjamin, S. R., Paim, R. T. T., Holanda, M. O., Silva, J. Y. G., Guedes, M. I. F. (2017). Hypolipidemic activity of P-methoxycinnamic diester (PCO - C) isolated from Copernicia prunífera against Triton WR-1339 and hyperlipidemic diet in mice. Environmental Toxicology and Pharmacology, 56 (2017), 198–203.
Freitas, C. A. S., de Sousa, P. H. M., Soares, D. J., da Silva, J. Y. G., Benjamin, S. Rathinaraj, & Guedes, M. I. F. (2019). Carnauba wax uses in food - a review. Food Chemistry, 291 (2019), 1-38
Freitas, C.A.S., Vieira, Í.G.P., Sousa, P.H.M., Muniz, C.R., Gonzaga, M.L.D.C. &, Guedes, M.I.F. (2016). Carnauba wax p-methoxycinnamic diesters: Characterisation, antioxidant activity and simulated gastrointestinal digestion followed by in vitro bioaccessibility. Food Chemistry, 196 (2016), 1293–1300.
Guedes, M. I. F., Alves, C. R., Vieira, I. G. P., Almeida, L. M., Mendes, F. N. P., Duarte, L. S. F., & Arruda Filho, A. C. V. Processo de produção, uso e composição farmacêutica compreendendo compostos obtidos a partir de cera de carnaúba (2011). [Production process, use and pharmaceutical composition of carnauba wax-derived products]. Patente BR 2011/1012429-2
Jakovetić, S. M., Jugović, B. Z., Gvozdenović, M. M., Bezbradica, D. I., Antov, M. G., Mijin, D. Ž., & Knežević-Jugović, Z. D. (2013). Synthesis of Aliphatic Esters of Cinnamic Acid as Potential Lipophilic Antioxidants Catalyzed by Lipase B from Candida antarctica. Applied Biochemistry and Biotechnology, 170(6), 1560–1573.
Kour, J., Ali, M. N., Ganaie, H. A., & Tabassum, N. (2017). Amelioration of the cyclophosphamide induced genotoxic damage in mice by the ethanolic extract of Equisetum arvense. Toxicology Reports, 4(2), 226–233.
Lorenzi, H., Noblick, L., Kahn, F., Ferreira, E. (2010). Brazilian flora Lorenzi: Arecaceae (palms). Instituto Plantarum de Estudos da Flora. Nova Odessa, 368 (2), 43-9.
Mamal, E., Basar, M., Uzun, H. & Seckin, I. Caffeic Acid Phenethyl Ester Prevents Mesengial Cell Apoptosis by Suppressing zp38MAPK Signal. J.Cytol. Histol. 3(2012), 4451-4475.
Matboli, M., Eissa, S., Ibrahim, D., Hegazy, M. G. A., Imam, S. S., & Habib, E. K. (2017). Caffeic Acid Attenuates Diabetic Kidney Disease via Modulation of Autophagy in a High-Fat Diet/Streptozotocin- Induced Diabetic Rat. Scientific Reports, 7(2017), 11-24.
Messias, J. B., Caraciolo, M. C. M., Oliveira, I. M. de, Montarroyos, U. R., Bastos, I. V. G. A., Guerra, M. de O., & Souza, I. A. (2010). Avaliação dos parâmetros hematológicos e bioquímicos de ratas no segundo terço da gestação submetidas à ação do extrato metanólico de Cereus jamacaru DC., Cactaceae. Revista Brasileira de Farmacognosia, 20(2010), 478–483.
Naqshbandi, A., Khan, M.W., Rizwan, S., Rehman, S.U., Khan, F. (2012). Studies on the protective effect of dietary fish oil on cisplatin-induced nephrotoxicity in rats. Food Chem Toxicol, 50(22), 265-273.
Organization for Economic Cooperation and Development. Guideline 425 for testing of chemicals. Paris: OECD, 1996.to
Ola, M. S., Ahmed, M. M., Ahmad, R., Abuohashish, H. M., Al-Rejaie, S. S., & Alhomida, A. S. (2015). Neuroprotective Effects of Rutin in Streptozotocin-Induced Diabetic Rat Retina. Journal of Molecular Neuroscience, 56(15), 440–448.
Paim, R.T.T., Benjamin, S.R., Rondina, D., Marques, M.M.M., de A. Viana, D., da C. Gonzaga, M.L., Vieira, Í.G.P., Mendes, F.N.P., Rodrigues, P.A.S., & Guedes, M.I.F. (2017). Antihypercholesterolemic effects of fruit aqueous extract of Copernicia prunifera (Miller) H. E. Moore in mice diet-induced hypercholesterolemia. Evidence-Based complement. Altern. Medicine, 2017(2017), 1–15.
Ping, K. Y, Darah, I., Chen, Y., Sreeramanan, & S., Sasidharan, S. (2013). Acute and subchronic toxicity study of Euphorbia hirta L. methanol extract in rats. Biomed. Res. Int., 2013(3), 1-14.
Pinto, M. C. L., Melo, M. M., Costa, M. E. R., & Labarrere, C. R. (2010). Hematological and biochemical profiles of rats submitted to experimental poisoning with Tityus serrulatus venom. Arquivo Brasileiro de Medicina Veterinária e Zootecnia, 62(10), pp. 350–356.
Rodrigues, P. A. S., Guedes, M. I. F., Marques, M. M. M., Silva, I. N. G. Da, & Vieira, Í. G. P. (2014). Hypoglycemic activity of Copernicia cerifera mart. Leaf powder extract in the treatment of alloxan-induced diabetic mice. International Journal of Pharmacy and Pharmaceutical Sciences, 6(14), 115–118.
Shi, H., Xie, D., Yang, R., & Cheng, Y. (2014). Synthesis of caffeic acid phenethyl ester derivatives, and their cytoprotective and neuritogenic activities in PC12 cells. J Agric Food Chem, 62(2), 5046-5053.
Sova, M., Zizak, Z., Stankovic, J., Prijatelj, M., Turk, S., Juranic, Z., Mlinaric-Rascan, I., & Gobec, S. (2013). Cinnamic Acid Derivatives Induce Cell Cycle Arrest in Carcinoma Cell Lines. Medicinal Chemistry, 9(2013), 633–641.
Taner, G., Özkan Vardar, D., Aydin, S., Aytaç, Z., Başaran, A., & Başaran, N. (2016). Use of in vitro assays to assess the potential cytotoxic, genotoxic and antigenotoxic effects of vanillic and cinnamic acid. Drug and Chemical Toxicology, 40(2016), 183–190.
Theodotou, M., Fokianos, K., Mouzouridou, A., Konstantinou, C., Aristotelous, A., Prodromou, D., Chrysikou, A. (2016). The effect of resveratrol on hypertension: A clinical trial. Experim. and Therap. Medic., 13 (6), 295–301.
Ullmann’s Encyclopedia of Industrial Chemistry, 5th Edition VCH: Weinheim, Germany. 1996/1997. Section A, 28 vols. Section B, 8 vols. DM 19 400 Organic Process Research & Development, 1 (1997), 391-392.
Vandenburg, L. E., & Wilder, E. A. (1970). The structural constituents of carnauba wax. J. Am. Oil Chem. Soc., 47(1), 514-518.
WHO. (2017) | Noncommunicable diseases. WHO. Doi:/entity/mediacentre/factsheets/fs355/en/index.html
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2020 Bruno Bezerra da Silva, Jose Ytalo Gomes da Silva, Natália do Vale Canabrava, Marcelo Oliveira Holanda, Carla Laine Silva Lima, Eridan Orlando Pereira Tramontina Florean, Icaro Gusmão Pinto Vieira, Márcia Maria Mendes Marques, Maria Izabel Florindo Guedes
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.
