Assessment of the cytotoxicity of coumarin-3-carboxylic acid in human erythrocytes
Keywords:Hemolysis; Osmotic Fragility; Toxicity Tests.
The erythrocyte is a cell type that is highly susceptible to lipid peroxidation and hemolysis. In vitro cytotoxicity tests are often used to screen and determine the toxicity of various compounds, primarily to investigate direct effects on membrane integrity. Coumarins (1,2-benzopyrone) are part of a group of heterocyclic compounds present in several plant families. Numerous biological activities have been demonstrated for coumarins and their derivatives, including anti-inflammatory, antioxidant, anticancer and antimicrobial properties. The aim of the present study was to investigate for the first time the toxic profile of a coumarin derivative, 3-coumarin carboxylic acid, in cytotoxicity assays involving human erythrocytes. Solutions containing 3-coumarin carboxylic acid at concentrations of 50, 100, 500 and 1000 µg/mL were prepared. Human blood samples of types A, B and O were collected from healthy volunteers and submitted to cytotoxicity assessment in the face of hemolytic and anti-hemolytic activity assays. The tested substance was able to reduce lysis on human erythrocytes of blood types A, B and O at all concentrations tested. In the osmotic fragility assay, 3-coumarin carboxylic acid was also able to protect human erythrocytes against hemolysis, in blood types A, B and O, at concentrations of 50µg/mL and 100µg/mL. The in vitro cytotoxicity results indicate that 3-coumarin carboxylic acid showed a low percentage of hemolysis for human erythrocytes of blood groups A, B and O when in direct contact with these cells, being also able to protect the erythrocyte membrane, preventing hemolysis.
Barot, K. P., Jain, S. V., Kremer, L., Singh, S., & Ghate, M. D. (2015). Recent advances and therapeutic journey of coumarins: current status and perspectives. Medicinal Chemistry Research, 24(7), 2771–2798. https://doi.org/10.1007/s00044-015-1350-8
Borges, F., Roleira, F., Milhazes, N., Santana, L., & Uriarte, E. (2005). Simple coumarins and analogues in medicinal chemistry: occurrence, synthesis and biological activity. Current Medicinal Chemistry, 12(8), 887–916. https://doi.org/10.2174/0929867053507315
Brandão, R., Lara, F. S., Pagliosa, L. B., Soares, F. A., Rocha, J. B. T., Nogueira, C. W., & Farina, M. (2005). Hemolytic Effects of Sodium Selenite and Mercuric Chloride in Human Blood. Drug and Chemical Toxicology, 28(4), 397–407. https://doi.org/10.1080/01480540500262763
Dacie, J. V., & Lewis, S. M. (2001). Practical Haematology. Harcourt Publishers Limited, 9th Editio, 444–451.
de Oliveira, S., & Saldanha, C. (2010). An overview about erythrocyte membrane. Clinical Hemorheology and Microcirculation, 44(1), 63–74. https://doi.org/10.3233/CH-2010-1253
Gomes Júnior, A. L., Islam, M. T., Nicolau, L. A. D., de Souza, L. K. M., Araújo, T. de S. L., Lopes de Oliveira, G. A., de Melo Nogueira, K., da Silva Lopes, L., Medeiros, J.-V. R., Mubarak, M. S., & Melo-Cavalcante, A. A. de C. (2020). Anti-Inflammatory, Antinociceptive, and Antioxidant Properties of Anacardic Acid in Experimental Models. ACS Omega, 5(31), 19506–19515. https://doi.org/10.1021/acsomega.0c01775
Jia, Q. (2003). Generating and Screening a Natural Product Library for Cyclooxygenase and Lipoxygenase Dual Inhibitors (pp. 643–718). https://doi.org/10.1016/S1572-5995(03)80016-9
Kalkhambkar, R. G., Kulkarni, G. M., Kamanavalli, C. M., Premkumar, N., Asdaq, S. M. B., & Sun, C. M. (2008). Synthesis and biological activities of some new fluorinated coumarins and 1-aza coumarins. European Journal of Medicinal Chemistry, 43(10), 2178–2188. https://doi.org/10.1016/j.ejmech.2007.08.007
Lee, S. H., Park, C., Jin, C.-Y., Kim, G.-Y., Moon, S.-K., Hyun, J. W., Lee, W. H., Choi, B. T., Kwon, T. K., Yoo, Y. H., & Choi, Y. H. (2008). Involvement of extracellular signal-related kinase signaling in esculetin induced G1 arrest of human leukemia U937 cells. Biomedicine & Pharmacotherapy, 62(10), 723–729. https://doi.org/10.1016/j.biopha.2007.12.001
Markowicz-Piasecka, M., Huttunen, K. M., Mikiciuk-Olasik, E., & Sikora, J. (2018). Biocompatible sulfenamide and sulfonamide derivatives of metformin can exert beneficial effects on plasma haemostasis. Chemico-Biological Interactions, 280, 15–27. https://doi.org/10.1016/j.cbi.2017.12.005
Mukherjee, A., Ghosh, S., Sarkar, R., Samanta, S., Ghosh, S., Pal, M., Majee, A., Sen, S. K., & Singh, B. (2018). Synthesis, characterization and unravelling the molecular interaction of new bioactive 4-hydroxycoumarin derivative with biopolymer: Insights from spectroscopic and theoretical aspect. Journal of Photochemistry and Photobiology B: Biology, 189, 124–137. https://doi.org/10.1016/j.jphotobiol.2018.10.003
Muñoz-Castañeda, J., Muntané, J., Muñoz, M. C., Bujalance, I., Montilla, P., & Túnez, I. (2006). Estradiol and catecholestrogens protect against adriamycin-induced oxidative stress in erythrocytes of ovariectomized rats. Toxicology Letters, 160(3), 196–203. https://doi.org/10.1016/j.toxlet.2005.07.003
Niki, E., Yamamoto, Y., Komuro, E., & Sato, K. (1991). Membrane damage due to lipid oxidation. The American Journal of Clinical Nutrition, 53(1), 201S-205S. https://doi.org/10.1093/ajcn/53.1.201S
Podsiedlik, M., Markowicz-Piasecka, M., & Sikora, J. (2020). Erythrocytes as model cells for biocompatibility assessment, cytotoxicity screening of xenobiotics and drug delivery. Chemico-Biological Interactions, 332, 109305. https://doi.org/10.1016/j.cbi.2020.109305
Pretorius, E., & Kell, D. B. (2014). Diagnostic morphology: biophysical indicators for iron-driven inflammatory diseases. Integr. Biol., 6(5), 486–510. https://doi.org/10.1039/C4IB00025K
Pretorius, E., Olumuyiwa-Akeredolu, O. O., Mbotwe, S., & Bester, J. (2016). Erythrocytes and their role as health indicator: Using structure in a patient-orientated precision medicine approach. Blood Reviews, 30(4), 263–274. https://doi.org/10.1016/j.blre.2016.01.001
Rangel, M., Malpezzi, E. L. A., Susini, S. M. M., & De Freitas, J. (1997). Hemolytic activity in extracts of the diatom Nitzschia. Toxicon, 35(2), 305–309. https://doi.org/10.1016/S0041-0101(96)00148-1
Schiar, V. P. P., dos Santos, D. B., Lüdtke, D. S., Vargas, F., Paixão, M. W., Nogueira, C. W., Zeni, G., & Rocha, J. B. T. (2007). Screening of potentially toxic chalcogens in erythrocytes. Toxicology in Vitro, 21(1), 139–145. https://doi.org/10.1016/j.tiv.2006.08.006
Shah, S. M. M., Sadiq, A., Shah, S. M. H., & Ullah, F. (2014). Antioxidant, total phenolic contents and antinociceptive potential of Teucrium stocksianum methanolic extract in different animal models. BMC Complementary and Alternative Medicine, 14(1), 181. https://doi.org/10.1186/1472-6882-14-181
Tyagi, Y. K., Kumar, A., Raj, H. G., Vohra, P., Gupta, G., Kumari, R., Kumar, P., & Gupta, R. K. (2005). Synthesis of novel amino and acetyl amino-4-methylcoumarins and evaluation of their antioxidant activity. European Journal of Medicinal Chemistry, 40(4), 413–420. https://doi.org/10.1016/j.ejmech.2004.09.002
Zhang, K., Ding, W., Sun, J., Zhang, B., Lu, F., Lai, R., Zou, Y., & Yedid, G. (2014). Antioxidant and antitumor activities of 4-arylcoumarins and 4-aryl-3,4-dihydrocoumarins. Biochimie, 107, 203–210. https://doi.org/10.1016/j.biochi.2014.03.014
How to Cite
Copyright (c) 2022 Humberto de Carvalho Aragão Neto; Aleson Pereira de Sousa; Maria Alice Araújo de Medeiros ; Millena de Souza Alves; Reinaldo Nóbrega de Almeida; Abrahão Alves de Oliveira Filho
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.