Evaluación del perfil citogenotóxico in vitro del complejo metálico de prata (I) con furosemida (Ag-FSE)

Autores/as

DOI:

https://doi.org/10.33448/rsd-v11i13.34986

Palabras clave:

Inestabilidad genômica; Complejo de plata; Toxicogenética; Citotoxicidad; Mutagenicidad.

Resumen

El objetivo del presente estudio fue evaluar el potencial citotóxico de un nuevo complejo de plata(I) con furosemida (Ag-FSE) en un panel de células tumorales y no tumorales humanas, así como su seguridad genotoxicológica. De acuerdo con los resultados obtenidos, la línea celular derivada del adenocarcinoma colorrectal (Caco-2) fue la más sensible al complejo Ag-FSE, y entre las células no tumorales se encontraban los fibroblastos no transformantes conocidos como GM07492A, lo que estimuló la caracterización. de las propiedades citotóxicas contra estas células. Además de interferir con el perfil metabólico celular (evidenciado por el método de resazurina), Ag-FSE altera la integridad de las membranas celulares (resultados obtenidos por el ensayo de azul de tripano) independientemente del linaje celular evaluado. Sin embargo, la interferencia con la capacidad clonogénica depende de la célula que se esté analizando; la actividad citotóxica evaluada por el ensayo de supervivencia clonogénica se evidenció frente a las células Caco-2, pero no frente a las células GM07492A. Además, Ag-FSE no indujo un aumento en la extensión del daño del ADN detectable por el ensayo Comet, ni en la frecuencia de micronúcleos en relación con el control negativo, lo que demuestra la ausencia de genotoxicidad en las condiciones experimentales utilizadas. Los datos del presente estudio brindan información sobre varios aspectos biológicos del complejo Ag-FSE y ayudan en la generación de nuevos candidatos a fármacos con potencial impacto en el área de la salud, con miras al tratamiento del cáncer.

Citas

Aquaroni, N. A. S., Nakahata, D. H., Lazarini, S. C., Resende, F. A., Cândido, A. L. P., Barud, H. S., Claro, A. M., Carvalho, J. E., Ribeiro, C. M., Pavan, F. R., Lustri, B. C., Ribeiro, T. R. M., Moreira, C. G., Cândido, T. Z., Lima, C. S. P., Ruiz, A. L. T. G., Corbi, P. P., & Lustri, W. R. (2020). Antibacterial activities and antiproliferative assays over a tumor cells panel of a silver complex with 4-aminobenzoic acid: Studies in vitro of sustained release using bacterial cellulose membranes as support. Journal of Inorganic Biochemistry, 212, 111247. https://doi.org/10.1016/j.jinorgbio.2020.111247

Barroso, M. B., Jiménez, R. M., Alonso, R. M., & Ortiz, E. (1996). Determination of piretanide and furosemide in pharmaceuticals and human urine by high-performance liquid chromatography with amperometric detection. Journal of Chromatography B., 675(2), 303-312. https://doi.org/10.1016/0378-4347(95)00349-5

Barry, N.P., & Sadler, P. J. (2013). Exploration of the medical periodic table: towards new targets. Chem Commun., 49(45), 5106-5131. https://doi.org/10.1039/c3cc41143e

Ciol, M. R., Manzano, C. M., Cuin, A., Pavan, F. R., Ribeiro, C. M., Ruiz, A. L. T. G., Oliveira, E. C. S., Lustri, W. R., Fregonezi, N. F., Nogueira, F. A. R., & Corbi, P. P. (2018). A Silver complex with cycloserine: synthesis, spectroscopic characterization, crystal structure and in vitro biological studies. ChemistrySelect., 3(6), 1719 -1726. https://doi.org/10.1002/slct.201703078

Cirri, D., Fabbrini, M. G., Pratesi, A., Ciofi, L., Massai, L., Marzo T., & Messori, L. (2019). The leading established metal-based drugs: a revisitation of their relevant physico-chemical data. Biometals, 32(5), 813-817. https://doi.org/10.1007/s10534-019-00210-7

Cohen, S. M. (2007). New approaches for medicinal applications of bioinorganic chemistry. Current Opinion in Chemical Biology, 11(2), 115-120. https://doi.org/10.1016/j.cbpa.2007.01.012

Demir¸ E., Vales, G., Kaya, B., Creus, A., & Marcos, R. (2011). Genotoxic analysis of silver nanoparticles in Drosophila. Nanotoxicology, 5(3), 417-424. https://doi.org/10.3109/17435390.2010.529176

Eliopoulos, P., & Mourelatos, D. (1998). Lack of genotoxicity of silver iodide in the SCE Assay in vitro, in vivo, and in the Ames/Microsome Test. Teratogenesis, Carcinogenesis and Mutagenesis, 18(6), 1520-6866. https://doi.org/10.1002/(sici)1520-6866(1998)18:6<303::aid-tcm4>3.0.co;2-9

Esteban-Parra, G. M., Méndez-Arriaga, J. M., Rodríguez-Diégueza, A., Quirós, M., Salas, J. M., & Sánchez-Moreno, M. (2019). High antiparasitic activity of silver complexes of 5,7-dimethyl-1,2,4-triazolo [1,5a] pyrimidine. Journal of Inorganic Biochemistry, 201, 110810. https://doi.org/10.1016/j.jinorgbio.2019.110810

Favarin, L. R. V., Oliveira, L. B., Silva, H., Micheletti, A. C., Pizzuti, L., Machulek-Júnior, A., Caires, A. R. L., Back, D. F., Lima, S. M., Andrade, L. H. C., Duarte, L. F. B., Pinto, L. M. C., & Casagrande, G. A. (2019). Sonochemical synthesis of highly luminescent silver complexes: Photophysical properties and preliminary in vitro antitumor and antibacterial assays. Inorganica Chimica Acta, 492, 235-242. https://doi.org/10.1016/j.ica.2019.04.043

Fenech, M. (2007). Cytokinesis-block micronucleus cytome assay. Nature Protocols, 2(5), 1084–1104. https://doi.org/10.1038/nprot.2007.77

Ghosh, S. (2019). Cisplatin: The first metal based anticancer drug. Bioorganic Chemistry, 88, 102925. https://doi.org/10.1016/j.bioorg.2019.102925

Iqbal, M. A., Haque, R. A., Nasri, S. F., Majid, M. A., Ahamed, M. B. K., Farsi, E., & Fatima, T. (2013). Potential of silver against human colon cancer: (synthesis, characterization and crystal structures of xylyl (Ortho, meta, & Para) linked bisbenzimidazolium salts and Ag(I)-NHC complexes: In vitro anticancer studies). Chemistry Central Journal, 27(7). https://doi.org/10.1186/1752-153X-7-27

Kirsch-Volders, M., Bonassi, S., Knasmueller, S., Holland, N., Bolognesi, C., & Fenech, M. F. (2014). Commentary: Critical questions, misconceptions and a road map for improving the use of the lymphocyte cytokinesis-block micronucleus assay for in vivo biomonitoring of human exposure to genotoxic chemicals-A HUMN project perspective. Mutation Research - Reviews in Mutation Research, 759(1), 49–58. https://doi.org/10.1016/j.mrrev.2013.12.001

Kizrak, Ü., Çiftçi, O., Ozdemir, I., Gürbüz, N., Düs¸Ünceli, S. D., Kaloglu, M., Mansour, L., Zaghrouba, F., Hamdi, N., & Ozdemir, I. (2019). Amine-fnctionalized silver and gold N-heterocyclic carbene complexes: Synthesis, characterization and antitumor properties. Journal of Organometallic Chemistry, 882, 26-32. https://doi.org/10.1016/j.jorganchem.2018.12.018

Liang, X., Luan, S., Yin, Z., He, M., He, C., Yin, L., Zou, Y., Yuan, Z., Li, L., Song, X., Lv, C., & Zhang, W. (2018). Recent advances in the medical use of silver complex. European Journal of Medicinal Chemistry, 157, 62-80. https://doi.org/10.1016/j.ejmech.2018.07.057

Lu, Y.; Liu, Y.; & Yang, C. Evaluating in vitro DNA damage using comet assay. Journal of Visualized Experiments, v. 2017, n. 128, p. 2–7, 2017. https://doi.org/10.3791/56450

Lustri, W. R., Lazarini, S. C., Lustri, B. C., Corbi, P. P., Silva, M. A. C., Nogueira, F. A. R., Aquino, R., Amaral, A. C., Filho, O. T., Massabni, A. C., & Barud, H. S. (2017) Spectroscopic characterization and biological studies in vitro of a new silver complex with furosemide: Prospective of application as an antimicrobial agent. Journal of Molecular Structure, 1134, 386-394. https://doi.org/10.1016/j.molstruc.2016.12.056

Mahapatra, D. K., Bharti, S. K., Asati, V., & Singh, S. K. (2019). Perspectives of medicinally privileged chalcone based metal coordination compounds for biomedical applications. European Journal of Medicinal Chemistry, 174, 142-158. https://doi.org/10.1016/j.ejmech.2019.04.032

Malode, S. J., Shetti, N. P., & Nandibewoor, S. T. (2011). Mechanistic aspects of oxidation of loop diuretic drug furosemide by Ag(III) periodate complex in alkali media: A kinetic approach. Main Group Chemistry, 10, 215-227. https://doi.org/10.3233/MGC-2011-0050

Manzano, C. M., Nakahata, D. H., Tenorio, J. C., Lustri, W. R., Nogueira, F. A. R., Aleixo, N. A., Gomes, P. S. S., Pavan, F. R., Grecco, J. A., Ribeiro, C. M., & Corbi, P. P. (2020) Silver complexes with fluoroanthranilic acid isomers: spectroscopic characterization, antimycobacterial activity and cytotoxic studies over a panel of tumor cells. Inorganica Chimica Acta, 502, ICA 119293. https://doi.org/10.1016/j.ica.2019.119293

Medici, S., Peana, M., Nurchi, V. M., Lachowicz, J. I., Crisponi, G., & Zoroddu, M. A. (2015). Noble metals in medicine: Latest advances. Coordination Chemistry Reviews, 284, 329-350. https://doi.org/10.1016/j.ccr.2014.08.002

Medici, S., Peana, M., Nurchi, V. M., Lachowicz, J. I., & Zoroddu, M. A. (2019). Medical uses of silver: history, myths, and scientific evidence. American Chemical Society, 62(13), 5923-6404. https://doi.org/10.1021/acs.jmedchem.8b01439

Milionis, I., Banti, C. N., Sainis, I., Raptopoulou, C. P., Psycharis, V., Kourkoumelis, N., & Hadjikakou, S. K. (2018). Silver ciprofoxacin (CIPAG): a successful combination of chemically modifed antibiotic in inorganic–organic hybrid. JBIC Journal of Biological Inorganic Chemistry, 23(5), 705-723. https://doi.org/10.1007/s00775-018-1561-9

Mjos, K. D., & Orvig, C. (2014). Metallodrugs in Medicinal Inorganic Chemistry. Chemical Reviews, 114(8), 4540-4563. https://doi.org/10.1021/cr400460s

Möhler, J. S., Sim, W.; Blaskovich, M. A. T.; Cooper, M. A.; & Ziora, Z. M. (2018). Silver bullets: A new lustre on an old antimicrobial agent. Biotechnology Advances, 36 (5), 1391-1411. https://doi.org/10.1016/j.biotechadv.2018.05.004

Mosconi, N., Giulidori, C., Velluti, F., Hure, E., Postigo, A., Borthagaray, G., Back, D. F., Torre, M. H., & Rizzotto, M. (2014) Antibacterial, Antifungal, Phytotoxic, and Genotoxic Properties of Two Complexes of AgI with Sulfachloropyridazine (SCP): X-ray Diffraction of [Ag(SCP)]n. ChemMedChem., 9(6), 1211-1220. https://doi.org/10.1002/cmdc.201400071

Oberemma, A.; Hansenb, U.; Böhmerta, L.; Meckerta, C.; Braeuninga, A.; Thünemannb, A. F.; & Lampena, A. (2016). Proteomic responses of human intestinal Caco-2 cells exposed to silver nanoparticles and ionic silver. Journal Applied Toxicology, 36, 404-413. https://doi.org/10.1002/jat.3231

OECD - Organisation for Economic Cooperation and Development (Adopted: 29 July 2016). OECD Guideline for the testing of chemicals. 487: in vitro mammalian cell micronucleus test.

Pereira, A. S., Shitsuka, D. M., Parreira, F. J., & Shitsuka, R. (2018). Metodologia da pesquisa científica.[e-book]. Santa Maria. Ed. UAB/NTE/UFSM. https://repositorio. ufsm. br/bitstream/handle

Plotnikov, E., Silnikov, V., Gapeyev, A., & Plotnikov, V. (2016) Investigation of DNA-damage and Chromosomal Aberrations in Blood Cells under the Influence of New Silver-based Antiviral Complex. Advanced Pharmaceutical Bulletin, 6(1), 71-74. https://doi.org/10.15171/apb.2016.011

Pracharova, J., Novohradsky, V., Kostrhunova, H., Starha, P., Travnicek, Z., Kasparkova, J., & Brabec, V. (2018). Half-sandwich Os(II) and Ru(II) bathophenanthroline complexes: anticancer drug candidates with unusual potency and cellular activity profile in highly invasive triple-negative breast cancer cells. Dalton Transactions, 47(35), 12197-12208. https://doi.org/10.1039/c8dt02236d

Rocha, C. S., Filho, L. F. O. B., Souza, A. E., Diniz, R., Denadai, A. M. L., Beraldo, H., & Teixeira, L. R. (2019). Structural studies and investigation on the antifungal activity of silver(I) complexes with 5-nitrofuran-derived hydrazones. Polyhedron, 170, 723-730. https://doi.org/10.1016/j.poly.2019.06.033

Rocha, D. P., Pinto, G.F., Ruggiero, R., Oliveira, C. A., Guerra, W., Fontes, A. P. S., Tavares, T.T., Marzano, I.M., & Maia, E.C.P. (2011). Coordenação de metais a antibióticos como uma estratégia de combate à resistência bacteriana. Química Nova, 34(1), 111-118. https://doi.org/10.1590/S0100-40422011000100022

Singh, N. P., McCoy, M.T., Tice, R.R., & Schneider, E.L. (1988). A simple technique for quantitation of low levels of DNA damage in individual cells. Experimental Cell Research, 175(1), 184–191. https://doi.org/10.1016/0014-4827(88)90265-0

Thompson, K. H., & Orvig, C. (2006). Metal complexes in medicinal chemistry: new vistas and challenges in drug design. Dalton Transactions, 6, 761-764. https://doi.org/10.1039/b513476e

Tice, R. R., Agurell, E., Anderson, D., Burlinson, B., Hartmann, A., Kobayashi, H., Miyamae, Y., Rojas, E., Ryu, J.C., & Sasaki, Y.F. (2000). Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology. Arch Environ Contam Toxicol, 35, 112–122. https://doi.org/10.1002/(sici)1098-2280(2000)35:3<206::aid-em8>3.0.co;2-j

Vila, L., Marcos, R., & Hernández, A. (2017) Long-term effects of silver nanoparticles in caco-2 cells. Nanotoxicology, 11(6), 771-780. https://doi.org/10.1080/17435390.2017.1355997

Yan, Z. H., Li, D., & Yin, X. B. (2017). Review for chiral-at-metal complexes and metal-organic framework enantiomorphs. Science Bulletin, 62(19), 1344-1354. https://doi.org/10.1016/j.scib.2017.09.013

Zande, M., Undas, A. K., Kramer, E., Monopoli, M. P., Peters, R. J., Garry, D., Fernandes, E. C. A., Hendriksen, P. J., Marvin, H. J. P., Peijnenburg Ad. A., & Bouwmeester, H. (2016) Different responses of Caco-2 and MCF-7 cells to silver nanoparticles are based on highly similar mechanisms of action. Nanotoxicology, 10(10), 1431-1441. https://doi.org/10.1080/17435390.2016.1225132

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Publicado

26/09/2022

Cómo citar

GASPAROTI, G. de C.; GOMES, P. S. da S. .; ALEIXO, N. A. .; SILVA, J. G. F. da .; CERQUEIRA, I. H. .; LUSTRI, W. R. .; RESENDE, F. A. Evaluación del perfil citogenotóxico in vitro del complejo metálico de prata (I) con furosemida (Ag-FSE). Research, Society and Development, [S. l.], v. 11, n. 13, p. e21111334986, 2022. DOI: 10.33448/rsd-v11i13.34986. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/34986. Acesso em: 25 nov. 2024.

Número

Sección

Ciencias de la salud