Assessment of the cytotoxicity of coumarin-3-carboxylic acid in human erythrocytes

Authors

DOI:

https://doi.org/10.33448/rsd-v11i7.29965

Keywords:

Hemolysis; Osmotic Fragility; Toxicity Tests.

Abstract

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.

References

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

Published

26/05/2022

How to Cite

ARAGÃO NETO, H. de C. .; SOUSA, A. P. de .; MEDEIROS , M. A. A. de .; ALVES, M. de S. .; ALMEIDA, R. N. de .; OLIVEIRA FILHO, A. A. de . Assessment of the cytotoxicity of coumarin-3-carboxylic acid in human erythrocytes. Research, Society and Development, [S. l.], v. 11, n. 7, p. e31711729965, 2022. DOI: 10.33448/rsd-v11i7.29965. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/29965. Acesso em: 13 nov. 2024.

Issue

Section

Health Sciences