Medidas para o controle da aflatoxina B1: uma breve revisão sobre o uso de flavonoides e argilas

Autores

  • Janaína Nones Universidade Federal de Santa Catarina
  • Humberto Gracher Riella Universidade Federal de Santa Catarina
  • Jader Nones Universidade Federal de Santa Catarina

DOI:

https://doi.org/10.5007/2175-7925.2017v30n1p1

Resumo

A aflatoxina B1 (AFB1) é uma das micotoxinas mais abundantes e tóxicas produzidas por cepas toxigênicas. Esta substância afeta a viabilidade celular, sendo capaz de induzir a morte, tanto de células humanas, quanto de células animais. Medidas vêm sendo adotadas para minimizar os danos causados pela AFB1, incluindo a utilização de flavonoides (compostos polifenólicos extraídos de plantas) e bentonitas (um tipo de argila). Nesta revisão, as características físico-químicas da AFB1 e seus efeitos em diferentes tipos de células, in vitro e in vivo, foram abordados. Além disso, a capacidade de proteção celular a partir de substâncias e materiais naturais, tais como flavonoides e bentonita, foi brevemente descrita. Também relatamos os efeitos econômicos causados pelas micotoxinas e sugerimos alternativas (flavonoides e bentonita) para novas abordagens terapêuticas visando combater a toxicidade causada por estas substâncias (AFB1).

Biografia do Autor

Janaína Nones, Universidade Federal de Santa Catarina

Possui doutorado (2016) em Engenharia Química (UFSC), mestrado (2012) em Ciência dos Alimentos (UFSC) e graduação em Química (UFSC), sendo portadora dos graus de Bacharel (2010) e Licenciatura (2010). Tem experiência na área de Química, Engenharia Química e Engenharia de Alimentos, com ênfase no desenvolvimento e caracterização de novos materiais e uso de técnicas analíticas para detecção e quantificação de substâncias tóxicas.

Humberto Gracher Riella, Universidade Federal de Santa Catarina

Graduado em Engenharia Química pela Universidade Federal do Paraná (1975), Mestrado em Tecnologia Nuclear pela Universidade de São Paulo (1978) e Doutorado em Maschinenbauingenier - Karlsruher Institut für Technologie (1983). Professor Titular Classe da Universidade Federal de Santa Catarina e do Programa de Pós-Graduação em Engenharia Química. Atua, principalmente, nos seguintes temas: Combustíveis Nucleares, Resíduos Sólidos Industriais, Processamento de Minerais metálicos, Materiais Antimicrobianos, Síntese de Materiais Nanoestruturados e Técnicas de Caracterização de Materiais.

Jader Nones, Universidade Federal de Santa Catarina

Atualmente é Professor voluntário do Departamento de Biologia Celular, Citologia e Genética da Universidade Federal de Santa Catarina (UFSC) e coordenador do Programa Estadual de Sanidade Suídea na Companhia Integrada de Desenvolvimento Agrícola de Santa Catarina (CIDASC). Realizou pós-doutorado (2012) em Biologia Celular e do Desenvolvimento pela UFSC, doutorado e mestrado em Ciências Morfológicas (2011 e 2008, respectivamente) pela Universidade Federal do Rio de Janeiro (UFRJ). Graduou-se em Medicina Veterinária pela Universidade do Estado de Santa Catarina - UDESC (2006) e Técnico em Agropecuária pela Escola Agrotécnica Federal de Rio do Sul (2002). Trabalhou na Empresa de Pesquisa Agropecuária e Extensão Rural (Epagri), exercendo a função de extensionista rural (2009/2010). Tem experiência em defesa sanitária animal e morfologia, com ênfase em histologia, fisiologia e embriologia.

Referências

ABBÈS, S.; SALAH-ABBÈS, J. B.; HETTA, M. M.; IBRAHIM, M.; ABDEL-WAHHAB, M. A.; BACHA, H.; OUESLATI, R. Eficacy of Tunisian montmorillonite for in vitro alatoxin binding and in vivo amelioration of physiological alterations. Applied Clay Science, Oxford, v. 42, n. 1-2, p. 151-157, 2008.

ABDEL-WAHHAB, M. A.; ALJAWISH, A.; EL-NEKEETY, A. A.; ABDEL-AIEZM, S. H.; ABDEL-KADER, H. A. M.; RIHN, B. H.; JOUBERT, O. Chitosan nanoparticles and quercetin modulate gene expression and prevent the genotoxicity of alatoxin B1 in rat liver. Toxicology Reports, Detroit, v. 2, p. 737-747, 2015.

ABDEL-WAHHAB, M. A.; ALY, S. E. Antioxidants and radical scavenging properties of vegetable extracts in rats fed alatoxincontaminated diet. Journal of Agricultural and Food Chemistry,

Washington, v. 51, n. 8, p. 2409-2414, 2003.

ABDEL-WAHHAB, M. A.; NADA, A. S.; KHALIL, F. A. Physiological and toxicological responses in rats fed alatoxincontaminated diet with or without sorbent materials. Animal Feed Science and Technology, Amsterdam, v. 97, n. 3-4, p. 209-219, 2002.

ABDEL-WAHHAB, M. A.; NADA, S. A.; FARAG, I. M.; ABBAS, N. F.; AMRA, H. A. Potential protective effect of HSCAS and bentonite against dietary alatoxicosis in rat: with special reference to chromosomal aberrations. Natural Toxins, New York, v. 6, n. 5,

p. 211-218, 1998.

AGAR, G.; ALPSOY, L.; BOZARI, S.; ERTURK, F. A.; YILDIRIM, N. Determination of protective role of selenium against alatoxin B1-induced DNA damage. Toxicology and Industrial Health, Princeton, v. 29, n. 5, p. 396-403, 2013.

AHLBERG, S. H.; JOUTSJOKI, V.; KORHONEN, H. J. Potential of lactic acid bacteria in alatoxin risk mitigation. International Journal of Food Microbiology, Amsterdam, v. 207, p. 87-102, 2015.

AJIBOYE, T. O.; ADELEYE, A. O.; SALAU, A. K.; OJEWUYI, O. B.; ADIGUN, N. S.; SABIU, S.; SUNMONU, T. O. Phenolic extract of Parkia biglobosa fruit pulp stalls alatoxin B1 – mediated oxidative rout in the liver of male rats. Brazilian Journal of Pharmacognosy, São Paulo, v. 24, n. 6, p. 668-676, 2014.

AJIBOYE, T. O.; RAJI, H. O.; MURITALA, H. F.; OJEWUYI, O. B.; YAKUBU, M. T. Anthocyanin extract of Lannea microcarpa fruits stall oxidative rout associated with alatoxin B1 hepatocarcinogenesis. Food Bioscience, Mysore, v. 4, p. 58-67, 2013.

ALMEIDA, P. A.; NONES, J.; TRENTIN, A.; NONES, J. Quercetin and rutin afect the survival and proliferation of human skin-derived multipotent mesenchymal stromal cells. Journal of Pharmacy and Pharmacology, London, v. 3, p. 237-242, 2015.

ANADÓN, A.; MARTÍNEZ, M. A.; ARES, I.; RAMOS, E.; CASTELLANO, V.; MARTÍNEZ, M.; MARTÍNEZLARRAÑAGA, M. R.; ROMERO, A. The food contaminants alatoxin B1 , fumonisin B1, ocratoxina, T-2 toxin and deoxynivalenol decrease intestinal barrier permeability in human Caco-2 cells, protector role of clay additives. Toxicology Letters, Amsterdam, v. 229S, S40-S252, 2014.

AUSTIN, K. J.; COCKRUM, R. R.; JONS, A. M.; ALEXANDER, B. M.; CAMMACK, K. M. Renin mRNA is upregulated in testes and testicular cells in response to treatment with alatoxin B1. Theriogenology, Los Altos, v. 77, n. 2, p. 331-337.e7, 2012.

AYUB, M. Y.; SACHAN, D. S. Dietary factors affecting alatoxin B1 carcinogenicity. Malaysian Journal of Nutrition, Kuala Lumpur, v. 3, p. 161-179, 1997.

BARCELOS, G. R. M.; GROTTO, D.; ANGELI, J. P. F.; SERPELONI, J. M.; ROCHA, B. A.; BASTOS, J. K.; BARBOSA JR, F. Evaluation of antigenotoxic effects of plant lavonoids quercetin and rutin on HepG2 Cells. Phytotherapy Research, London, v. 25, n. 9, p. 1381-1388, 2011.

BEDARD, L. L.; MASSEY, T. E. Alatoxin B1 -induced DNA damage and its repair. Cancer Letters, Virginia, v. 241, n. 2, p. 174-183, 2006.

BERNABUCCI, U.; COLAVECCHIA, L.; DANIELI, P. P.; BASIRICÒ, L.; LACETERA, N.; NARDONE, A.; RONCHI, B. Alatoxin B1 and fumonisin B1 affect the oxidative status of bovine peripheral blood mononuclear cells. Toxicology in Vitro, Oxford, v. 25, n. 3, p. 684-691, 2011.

BHATNAGAR-MATHUR, P.; SUNKARA, S.; BHATNAGARPANWAR, M.; WALIYAR, F.; SHARMA, K. K. Biotechnological advances for combating Aspergillus lavus and alatoxin contamination in crops. Plant Science, Davies, v. 234, p. 119-132, 2015.

BOUHLEL, I.; LIMEM, I.; SKANDRANI, I.; NEFATTI, A.; GHEDIRA, K.; DIJOUX-FRANCA, M. G.; LEILA, C. G. Assessment of isorhamnetin 3-O-neohesperidoside from Acacia alicina: protective effects toward oxidation damage and genotoxicity induced by alatoxin B1 and nifuroxazide. Journal of Applied Toxicology, Philadelphia, v. 30, n. 6, p. 551-558, 2010.

CHAN, H.; CHAN, C.; HO, J. W. Inhibition of glycyrrhizic acid on alatoxin B1 -induced cytotoxicity in hepatoma cells. Toxicology, Amsterdam, v. 188, n. 2-3, p. 211-217, 2003.

CHOI, K. C.; CHUNG, W. T.; KWON, J. K.; JANG, Y. S.; YU, J. Y.; PARK, S. M.; LEE, J. C. Chemoprevention of a lavonoid fraction from Rhus vernicilua Stokes on alatoxin B1-induced hepatic damage in mice. Journal of Applied Toxicology, Philadelphia, v. 31, n. 2, p. 150-156, 2011.

CHOI, K. C.; LEE, B. S.; CHUNG, W. T.; CHOI, M. S.; LEE, J. C. Protective effects of apigenin and quercetin on alatoxin b1-induced immunotoxicity in mice. Food Science and Biotechnology, Dordrecht, v. 19, n. 4, p. 987-992, 2010.

COSTA, S.; UTAN, A.; SPERONI, E.; CERVELLATI, R.; PIVA, G.; PRANDINI, A.; GUERRA, M. C. Carnosic acid from rosemary extracts: a potential chemoprotective agent against alatoxin B1 an in vitro study. Journal of Applied Toxicology, Philadelphia, v. 27, n. 2, p. 152-159, 2007.

DAKOVIĆ, A.; MATIJAŠEVIĆ, S.; ROTTINGHAUS, G. E.; LEDOUX, D. R.; BUTKERAITIS, P.; SEKULIĆ, Ž. Alatoxin B1 adsorption by natural and copper modiied montmorillonite. Colloids and Surfaces B Biointerfaces, Amsterdam, v. 66, n. 1, p. 20-25, 2008.

DIAO, E.; HOU, H.; DONG, H. Ozonolysis mechanism and inluencing factors of alatoxin B1 : a review. Trends in Food Science & Technology, Cambridge, v. 33, n. 1, p. 21-26, 2013.

EL-GIBALY, I.; MEKI, A. M. A.; ABDEL-GHAFFAR, S. K. Novel B melatonin-loaded chitosan microcapsules: in vitro characterization and antiapoptosis eficacy for alatoxin B1-induced apoptosis in rat liver. International Journal of Pharmaceutics, Amsterdam, v. 260, n. 1, p. 5-22, 2003.

EL-NEKEETY, A. A.; ABDEL-AZEIM, S. H.; HASSAN, A. M.; HASSAN, N. S.; ALY, S. E.; ABDEL-WAHHAB, M. A. Quercetin inhibits the cytotoxicity and oxidative stress in liver of rats fed alatoxin-contaminated diet. Toxicology Reports, Detroit, v. 1, p. 319-329, 2014.

EWUOLA, E. O.; JIMOH, O. A.; BELLO, A. D.; BOLARINWA, A. O. Testicular biochemicals, sperm reserves and daily sperm production of West African dwarf bucks fed varied levels of dietary alatoxin. Animal Reproduction Science, Amsterdam, v. 148, n. 3-4, p. 182-187, 2014.

FRANCIS, A. R.; SHETTY, T. K.; BHATTACHARYA, R. K. Modifying role of dietary factors on the mutagenicity of alatoxin B1: in vitro effect of plant lavonoids. Mutation Research, Amsterdam, v. 222, n. 4, p. 393-401, 1989.

GIORDANO, B. N. E.; NONES, J.; SCUSSEL, V. M. Susceptibility of the in shell Brazil nut mycolora and alatoxin cantamination to ozone gas treatment during storage. Journal of Agricultural Science, Cambridge, v. 4, n. 8, p. 1-10, 2012.

GOLLI-BENNOUR, E. E.; KOUIDHI, B.; BOUSLIMI, A.; ABID-ESSEFI, S.; HASSEN, W.; BACHA, H. Cytotoxicity and genotoxicity induced by alatoxin B1, ochratoxin A, and their combination in cultured Vero cells. Journal of Biochemical and Molecular Toxicology, New York, v. 24, n. 1, p. 42-50, 2010.

HANIOKA, N.; NONAKA, Y.; SAITO, K.; NEGISHI, T.; OKAMOTO, K.; KATAOKA, H.; NARIMATSU, S. Effect of alatoxin B1 on UDP-glucuronosyltransferase mRNA expression in HepG2 cells. Chemosphere, Oxford, v. 89, n. 5, p. 526-529, 2012.

HARUTYUNYAN, T.; HOVHANNISYAN, G.; BABAYAN, N.; OTHMAN, M. A.; LIEHR, T.; AROUTIOUNIAN, R. Inluence of alatoxin B1 on copy number variants in human leukocytes in vitro. Molecular Cytogenetics, London, v. 8, p. 1-5, 2015.

HUUSKONEN, P.; MYLLYNEN, P.; STORVIK, M.; PASANEN, M. The effects of alatoxin B1 on transporters and steroid metabolizing enzymes in JEG-3 cells. Toxicology Letters, Amsterdam, v. 218, n. 3, p. 200-206, 2013.

HUWIG, A.; FREIMUND, S.; KÄPPELI, O.; DUTLER, H. Mycotoxin detoxication of animal feed by different adsorbents. Toxicology Letters, Amsterdam, v. 122, n. 2, p. 179-188, 2001.

ITO, Y.; OHNISHI, S.; FUJIE, K. Chromosome aberrations induced by alatoxin B1 in rat bone marrow cells in vivo and their suppression by green tea. Mutation Research, Amsterdam, v. 222, n. 3, p. 253-261, 1989.

JAYNES, W. F.; ZARTMAN, R. E. Alatoxin toxicity reduction in feed by enhanced binding to surface-modiied clay additives. Toxins, Basel, v. 3, n. 6, p. 551-565, 2011.

KOHLI, E.; RAJ, H. G.; KUMARI, R.; ROHIL, V.; KAUSHIK, N. K.; PRASAD, A. K.; PARMAR, V. S. Comparison of the prevention of alatoxin b1-induced genotoxicity by quercetin and quercetin pentaacetate. Bioorgic & Medicinal Chemistry Letters, Oxford, v. 12, n. 18, p. 2579-2582, 2002.

LANGESWARAN, K.; REVATHY, R.; KUMAR, S. G. Kaempferol ameliorates alatoxin B1 (AFB1) induced hepatocellular carcinoma through modifying metabolizing enzymes, membrane bound ATPases and mitochondrial TCA cycle enzymes. Asian Paciic Journal of Tropical Biomedicine, Haikou, v. 2, n. 3, p. S1653-S1659, 2012.

LEE, J. K.; CHOI, E. H.; LEE, K. G.; CHUN, H. S. Alleviation of alatoxin B1-induced oxidative stress in HepG2 cells by volatile extract from Allii Fistulosi Bulbus. Life Sciences, Elmsford, v. 77, n. 23, p. 2896-2910, 2005.

LEE, S. E.; CAMPBELL, B. C.; MOLYNEUX, R. J.; HASEGAWA, S.; LEE, H. S. Inhibitory effects of naturally occurring compounds on alatoxin B1 biotransformation. Journal of Agricultural and Food Chemistry, Washington, v. 49, n. 11, p. 5171-5177, 2001.

LIU, Y.; WU, F. Global burden of alatoxin-induced hepatocellular carcinoma: a risk assessment. Environmental Health Perspectives, Weston Parkway Cary, v. 118, n. 6, p. 818-824, 2010.

MADRIGAL-SANTILLÁN, E.; MORALES-GONZÁLEZ, J. A.; VARGAS-MENDOZA, N.; REYES-RAMÍREZ, P.; CRUZJAIME, S.; SUMAYA-MARTÍNEZ, T.; PÉREZ-PASTÉN, R.; MADRIGAL-BUJAIDAR, E. Antigenotoxic studies of different substances to reduce the DNA damage induced by alatoxin B1 and ochratoxin A. Toxins, Basel, v. 2, n. 4, p. 738-757, 2010.

MARNEWICK, J. L.; GELDERBLOM, W. C.; JOUBERT, E. An investigation on the antimutagenic properties of South African herbal teas. Mutation Research, Amsterdam, v. 471, n. 1-2, p. 157-166, 2000.

MULDER, J. E.; BONDY, G. S.; MEHTA, R.; MASSEY, T. E. Up-regulation of nucleotide excision repair in mouse lung and liver following chronic exposure to alatoxin B1 and its dependence on

p53 genotype. Toxicology and Applied Pharmacology, v. 275, n. 2, p. 96-103, 2014.

MULDER, J. E.; BONDY, G. S.; MEHTA, R.; MASSEY, T. E. The impact of chronic Alatoxin B1 exposure and p53 genotype on base excision repair in mouse lung and liver. Mutation Research, Amsterdam, v. 773, p. 63-68, 2015.

MURRAY, H. H. Bentonite applications. In: MURRAY, H. H. (Ed.). Developments in Clay Science. Amsterdam: Elsevier, 2006. p. 111-130.

NONES, J.; COSTA, A. P.; LEAL, R. B.; GOMES, F. C. A.; TRENTIN, A. G. The lavonoids hesperidin and rutin promote neural crest cell survival. Cell and Tissue Research, Berlin, v. 350, n. 2, p. 305-315, 2012a.

NONES, J.; DE SAMPAIO SPOHR, T. C. L.; GOMES, F. C. A. Effects of the lavonoid hesperidin in cerebral cortical progenitors in vitro: indirect action through astrocytes. International Journal of Developmental Neuroscience, Oxford, v. 30, n. 4, p. 303-313, 2012b.

NONES, J.; NONES, J.; POLI, A.; TRENTIN, A.G. ; RIELLA, H. G. ; Kuhnen, N. C. . Organophilic treatments of bentonite increase the adsorption of alatoxin B1 and protect stem cells against cellular damage. Colloids and Surfaces. B, Biointerfaces (Print), Amsterdam,v. 145, p. 555-561, 2016.

NONES, J.; NONES, J.; RIELLA, H. G.; KUHNEN, N. C.; TRENTIN, A. Bentonite protects neural crest stem cells from death caused by alatoxin B1. Applied Clay Science, Oxford, v. 104, n. 119-127, 2015a.

NONES, J.; NONES, J.; RIELLA, H. G.; POLI, A.; TRENTIN, A. G.; KUHEN, N. C. Thermal treatment of bentonite reduces alatoxin b1 adsorption and affects stem cell death. Materials Science & Engineering C, Amsterdam, v. 55, p. 530-537, 2015b.

NONES, J.; NONES, J.; TRENTIN, A. The lavonoid hesperidin protects neural crest cells from death caused by alatoxin B1. Cell and Tissue Research, Berlin, v. 37, n. 2, p. 181-186, 2013.

NONES, J.; NONES, J.; TRENTIN, A. Rutin increases melanocytes survival against the damage caused by mycotoxin AFB1. Biotemas, Florianópolis, v. 28, n. 4, p. 1-8, 2015d.

NONES, J.; RIELLA, H. G.; TRENTIN, A. G.; NONES, J. Effects of bentonite on different cell types: a brief review. Applied Clay Science, Oxford, v. 105-106, p. 225-230, 2015c.

NONES, J.; SAMPAIO, E; SPOHR, T. C. L.; GOMES, F. C. A. Hesperidin, a lavone glycoside, as mediator of neuronal survival. Neurochemical Research, New York, v. 36, n. 10, p. 1776-1784, 2011.

PUNVITTAYAGUL, C.; SRINGARM, K.; CHAIYASUT, C.; WONGPOOMCHAI, R. Mutagenicity and antimutagenicity of hydrophilic and lipophilic extracts of Thai northern purple rice. Asian Paciic Journal of Cancer Prevention, Bangkok, v. 15, n. 21, p. 9517-9522, 2014.

RODRIGUES, L. A. S.; FIGUEIRAS, A.; VEIGA, F.; FREITAS, R. M.; NUNES, L. C. C.; SILVA FILHO, E. C.; LEITE, C. M. S. The systems containing clays and clay minerals from modiied drug release: a review. Colloids and Surface B, cidade, v. 103, p. 642-651, 2013.

SHEN, H. M.; ONG, C. N.; SHI, C. Y. Involvement of reactive oxygen species in alatoxin B1-induced cell injury in cultured rat hepatocytes. Toxicology, Amsterdam, v. 99, n. 1-2, p. 115-123, 1995.

SIESS, M. H.; LE BON, A. M.; CANIVENC-LAVIER, M. C.; SUSCHETET, M. Mechanisms involved in the chemoprevention of lavonoids. Biofactors, Oxford, v. 12, n. 1-4, p. 193-199, 2000.

SMELA, M. E.; CURRIER, S. S.; BAILEY, E. A.; ESSIGMANN, J. M. The chemistry and biology of alatoxin B(1): from mutational spectrometry to carcinogenesis. Carcinogenesis, Oxford, v. 22, n. 4, p. 535-545, 2001.

TIRMENSTEIN, M. A.; MANGIPUDY, R. Alatoxin. In: PHILIP, W. (Ed.). Encyclopedia of Toxicology. Amsterdam: Elsevier, 2014. p. 104-106.

TREBAK, F.; ALAOUI, A.; ALEXANDRE, D.; EL OUEZZANI, S.; ANOUAR, Y.; CHARTREL, N.; MAGOUL, R. Impact of alatoxin B1 on hypothalamic neuropeptides regulating feeding behavior. Neurotoxicology, New York, v. 49, p. 165-173, 2015.

TURKEZ, H.; SISMAN, T. Anti-genotoxic effect of hydrated sodium calcium aluminosilicate on genotoxicity to human lymphocytes induced by alatoxin B1. Toxicology and Industrial Health, Princeton, v. 23, n. 2, p. 83-89, 2007.

TURKEZ, H.; SISMAN, T. The genoprotective activity of resveratrol on alatoxin B1-induced DNA damage in human lymphocytes in vitro. Toxicology and Industrial Health, Princeton, v. 28, n. 5, p. 474-480, 2012.

WANG, C. J.; HSU, J. D.; LIN, J. K. Suppression of alatoxin B1-induced hepatotoxic lesions by crocetin (a natural carotenoid). Carcinogenesis, Oxford, v. 12, n. 10, p. 1807-1810, 1991.

WANG, T.; LI, C.; LIU, Y.; LI, T.; ZHANG, J.; YONGHAI, S. Inhibition effects of Chinese cabbage powder on alatoxin B1-induced liver cancer. Food Chemistry, Reading, v. 186, p. 13-19, 2015.

WILLIAMS, J. H.; PHILLIPS, T. D.; JOLLY, P. E.; STILES, J. K.; JOLLY, C. M.; AGGARWAL, D. Human alatoxicosis in developing countries: a review of toxicology, exposure, potential health consequences, and interventions. The American Journal of Clinical Nutrition, Bethesda, v. 80, p. 1106-1122, 2004.

WU, Y. Z.; LU, F. P.; JIANG, H. L.; TAN, C. P.; YAO, D. S.; XIE, C. F.; LIU, D. L. The furofuran-ring selectivity, hydrogen peroxideproduction and low Km value are the three elements for highly effective detoxiication of alatoxin oxidase. Food and Chemical Toxicology, Oxford, v. 76, p. 125-131, 2015.

ZHANG, J.; ZHENG, N.; LIU, J.; LI, F. D.; LI, S. L.; WANG, J. Q. Alatoxin B1 and alatoxin M1 induced cytotoxicity and DNA damage in differentiated and undifferentiated Caco-2 cells. Food and Chemical Toxicology, Oxford, v. 83, p. 54-60, 2015.

Downloads

Publicado

2017-02-21

Edição

v. 30 n. 1 (2017)

Seção

Artigos

Licença

Direitos Autorais para artigos publicados nesta revista são do autor, com direitos de primeira publicação para a revista. Em virtude de aparecerem nesta revista de acesso público, os artigos são de uso gratuito, com atribuições próprias, em aplicações educacionais. 

Autores têm autorização para assumir contratos adicionais separadamente, para distribuição não-exclusiva da versão do trabalho publicada nesta revista (ex.: publicar em repositório institucional ou como capítulo de livro), com reconhecimento de autoria e publicação inicial nesta revista.

Esta obra foi licenciada com uma Licença Creative Commons Atribuição 4.0 Internacional - CC BY 

Licença Creative Commons