Avaliação do perfil citogenotóxico in vitro do complexo metálico de prata(I) com furosemida (Ag-FSE)

Autores

DOI:

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

Palavras-chave:

Instabilidade genômica; Complexo de prata; Toxicogenética; Citotoxicidade; Mutagenicidade.

Resumo

O objetivo do presente estudo foi avaliar o potencial citotóxico de um novo complexo de prata(I) com furosemida (Ag-FSE) sobre um painel de células humanas tumorais e não tumorais, bem como sua segurança genotoxicológica. De acordo com os resultados obtidos, a linhagem celular derivada do adenocarcinoma colorretal (Caco-2) foi a mais sensível ao complexo Ag-FSE, e dentre as células não tumorais foram fibroblastos não transformantes conhecidos como GM07492A, o que estimulou a caracterização das propriedades citotóxicas contra essas células. Além de interferir no perfil metabólico celular (evidenciado pelo método da resazurina), Ag-FSE altera a integridade das membranas celulares (resultados obtidos pelo ensaio do azul de Trypan) independentemente da linhagem celular avaliada. No entanto, a interferência na capacidade clonogênica depende da célula que está sendo testada; a atividade citotóxica avaliada pelo ensaio de sobrevivência clonogênica foi evidenciada contra células Caco-2, mas não contra células GM07492A. Além disso, Ag-FSE não induziu aumento na extensão do dano ao DNA detectável pelo ensaio Cometa, nem na frequência de micronúcleos em relação ao controle negativo, demonstrando ausência de genotoxicidade nas condições experimentais utilizadas. Os dados do presente estudo fornecem informações sobre diversos aspectos biológicos do complexo Ag-FSE e auxiliam na geração de novos candidatos a fármacos com potencial de impacto na área da saúde, visando o tratamento do câncer.

Referências

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

Downloads

Publicado

26/09/2022

Como 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. Avaliação do perfil citogenotóxico in vitro do complexo metálico de prata(I) com 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.

Edição

Seção

Ciências da Saúde