Protective effects of the flavonoid chrysin against methylmercury-induced genotoxicity and alterations of antioxidant status, in vivo

Oxidative Medicine and Cellular Longevity

Volumn 2015, Issue , 2015, Pages

  Manzolli, Eduardo Scandinari ^a   Serpeloni, Juliana Mara ^a   Grotto, Denise ^a   Bastos, Jairo Kennup ^a   Antunes, Lusânia Maria Greggi ^a   Barbosa, Fernando ^a   Barcelos, Gustavo Rafael Mazzaron ^a  

^a UNIVERSITY OF SÃO PAULO   (Brazil)

Author keywords

[No Author keywords available]

Indexed keywords

ANIMALS; ANTIOXIDANTS;

ADVERSE HEALTH EFFECTS; ANTIOXIDANT EFFECT; ANTIOXIDANT PROPERTIES; ANTIOXIDANT STATUS; GENOTOXICITIES; OXIDATIVE DAMAGE; PHYTOCHEMICALS; PROTECTIVE EFFECTS;

FLAVONOIDS;

CHRYSIN; GLUTATHIONE; METHYLMERCURY; ANTIOXIDANT; FLAVONOID; METHYLMERCURIC CHLORIDE; METHYLMERCURY DERIVATIVE; PROTECTIVE AGENT;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIOXIDANT ACTIVITY; ARTICLE; COMET ASSAY; COMPARATIVE STUDY; CONTROLLED STUDY; DNA DAMAGE; GENOTOXICITY; LEUKOCYTE; LIVER CELL; MALE; NONHUMAN; OXIDATIVE STRESS; PROTECTION; PROTEIN BLOOD LEVEL; RAT; ANIMAL; CYTOLOGY; DRUG EFFECTS; METABOLISM; WISTAR RAT;

ANIMALIA; PASSIFLORA EDULIS; RATTUS NORVEGICUS;

ANIMALS; ANTIOXIDANTS; COMET ASSAY; DNA DAMAGE; FLAVONOIDS; GLUTATHIONE; HEPATOCYTES; LEUKOCYTES; MALE; METHYLMERCURY COMPOUNDS; OXIDATIVE STRESS; PROTECTIVE AGENTS; RATS; RATS, WISTAR;

EID: 84924565896     PISSN: 19420900     EISSN: 19420994     Source Type: Journal    
DOI: 10.1155/2015/602360     Document Type: Article

References (128)

1. R. H. Liu, "Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals," The American journal of Clinical Nutrition, vol. 78, supplement 3, pp. S517-S520, 2003.
2. Y. J. Surh, "Cancer chemoprevention with dietary phytochemicals," Nature Reviews Cancer, vol. 3, no. 10, pp. 768-780, 2003.
3. T. M. de Kok, S. G. van Breda, and M. M. Manson, "Mechanisms of combined action of different chemopreventive dietary compounds: a review," European journal of Nutrition, vol. 47, supplement 2, pp. 51-59, 2008.
4. M.-T. Huang, R. L. Chang, A. W. Wood et al, "Inhibition of the mutagenicity of bay-region diol-epoxides of polycyclic aromatic hydrocarbons by tannic acid, hydroxylated anthraquinones and hydroxylated cinnamic acid derivatives," Carcinogenesis, vol. 6, no. 2, pp. 237-242, 1985.
5. G. R. M. Barcelos, J. P. F. Angeli, J. M. Serpeloni et al., "Quercetin protects human-derived liver cells against mercury-induced DNA-damage and alterations of the redox status," Mutation Research/Genetic Toxicology and Environmental Mutagenesis, vol. 726, no. 2, pp. 109-115, 2011.
6. J. M. Serpeloni, G. R. M. Barcelos, J. P. Friedmann Angeli, A. Z. Mercadante, M. Lourdes Pires Bianchi, and L. M. Greggi Antunes, "Dietary carotenoid lutein protects against DNA damage and alterations of the redox status induced by cisplatin in human derived HepG2 cells," Toxicology in Vitro, vol. 26, no. 2, pp. 288-294, 2012.
7. Z. Sahhugi, S. M. Hasenan, and Z. Jubri, "Protective effects of gelam honey against oxidative damage in young and aged rats," Oxidative Medicine and Cellular Longevity, vol. 2014, Article ID 673628, 8 pages, 2014.
8. E. Brown, N. S. Hurd, S. McCall, and T. E. Ceremuga, "Evaluation of the anxiolytic effects of chrysin, a Passiflora incarnata extract, in the laboratory rat," AANA journal, vol. 75, no. 5, pp. 333-337, 2007
9. S. K. Jaganathan and M. Mandai, "Antiproliferative effects of honey and of its polyphenols: a review," journal of Biomedicine and Biotechnology, vol. 2009, Article ID 830616, 13 pages, 2009.
10. P. Premratanachai and C. Chanchao, "Review of the anticancer activities of bee products," Asian Pacific journal of Tropical Biomedicine, vol. 4, no. 5, pp. 337-344, 2014.
11. J. Lachman, A. Hejtmánková, J. Sýkora, J. Karban, M. Orsák, and B. Rygerová, "Contents of major phenolic and flavonoid antioxidants in selected Czech honey," Czech journal of Food Sciences, vol. 28, no. 5, pp. 412-426, 2010.
12. M.-H. Siess, A.-M. Le Bon, M.-C. Canivenc-Lavier et al., "Flavonoids of honey and propolis: characterization and effects on hepatic drug-metabolizing enzymes and benzo[a]pyrene-DNA binding in rats," journal of Agricultural and Food Chemistry, vol. 44, no. 8, pp. 2297-2301, 1996.
13. M. Uhl, S. Ecker, F. Kassie et al., "Effect of chrysin, a flavonoid compound, on the mutagenic activity of 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and benzo(a)pyrene (B(a)P) in bacterial and human hepatoma (HepG2) cells," Archives of Toxicology, vol. 77, no. 8, pp. 477-484, 2003.
14. K. V. Anand, M. S. Mohamed Jaabir, P. A. Thomas, and P. Géraldine, "Protective role of chrysin against oxidative stress in d-galactose-induced aging in an experimental rat model," Geriatrics and Gerontology International, vol. 12, no. 4, pp. 741-750, 2012.
15. B. E. Milien and P. A. Quatromoni, "Nutritional research within the Framingham Heart Study," The journal of Nutrition Health and Aging, vol. 5, no. 3, pp. 139-143, 2001.
16. S. P. Whelton, J. He, P. K. Whelton, and P. Muntner, "Metaanalysis of observational studies on fish intake and coronary heart disease," The American journal of Cardiology, vol. 93, no. 9, pp. 1119-1123, 2004.
17. T. W. Clarkson, "The three modern faces of mercury," Environmental Health Perspectives, vol. 110, supplement 1, pp. 11-23, 2002.
18. T. W. Clarkson and L. Magos, "The toxicology of mercury and its chemical compounds," Critical Reviews in Toxicology, vol. 36, no. 8, pp. 609-662, 2006.
19. A. M. Visnjevec, D. Kocman, and M. Horvat, "Human mercury exposure and effects in Europe," Environmental Toxicology and Chemistry, vol. 33, no. 6, pp. 1259-1270, 2014.
20. H. M. Chan and G. M. Egeland, "Fish consumption, mercury exposure, and heart diseases," Nutrition Reviews, vol. 62, no. 2, pp. 68-72, 2004.
21. D. Grotto, J. Valentini, J. M. Serpeloni et al., "Evaluation of toxic effects of a diet containing fish contaminated with methylmercury in rats mimicking the exposure in the Amazon riverside population," Environmental Research, vol. 111, no. 8, pp. 1074-1082, 2011.
22. A. H. Stern, "A review of the studies of the cardiovascular health effects of methylmercury with consideration of their suitability for risk assessment," Environmental Research, vol. 98, no. 1, pp. 133-142, 2005.
23. S. A. Counter and L. H. Buchanan, "Mercury exposure in children: a review," Toxicology and Applied Pharmacology, vol. 198, no. 2, pp. 209-230, 2004.
24. C. Johansson, A. E Castoldi, N. Onishchenko, L. Manzo, M. Vahter, and S. Ceccatelli, "Neurobehavioural and molecular changes induced by methylmercury exposure during development," Neurotoxicity Research, vol. 11, no. 3-4, pp. 241-260, 2007
25. M. R. Karagas, A. L. Choi, E. Oken et al., "Evidence on the human health effects of low-level methylmercury exposure," Environmental Health Perspectives, vol. 120, no. 6, pp. 799-806, 2012.
26. A. L. Choi, P. Weihe, E. Budtz-Jørgensen et al., "Methylmercury exposure and adverse cardiovascular effects in Faroese whaling men," Environmental Health Perspectives, vol. 117, no. 3, pp. 367-372, 2009.
27. M. C. Houston, "Role of mercury toxicity in hypertension, cardiovascular disease, and stroke," The journal of Clinical Hypertension, vol. 13, no. 8, pp. 621-627, 2011.
28. M. Farina, M. Aschner, and J. B. T. Rocha, "Oxidative stress in MeHg-induced neurotoxicity," Toxicology and Applied Pharmacology, vol. 256, no. 3, pp. 405-417, 2011.
29. D. Joshi, M. D. Kumar, S. A. Kumar, and S. Sangeeta, "Reversal of methylmercury-induced oxidative stress, lipid peroxidation, and DNA damage by the treatment of N-acetyl cysteine: a protective approach," journal of Environmental Pathology, Toxicology and Oncology, vol. 33, no. 2, pp. 167-182, 2014.
30. C. J. S. Passos, D. S. da Silva, M. Lemire et al., "Daily mercury intake in fish-eating populations in the Brazilian Amazon," journal of Exposure Science and Environmental Epidemiology, vol. 18, no. 1, pp. 76-87, 2008.
31. G. R. M. Barcelos, D. Grotto, J. M. Serpeloni et al., "Protective properties of quercetin against DNA damage and oxidative stress induced by methylmercury in rats," Archives of Toxicology, vol. 85, no. 9, pp. 1151-1157, 2011.
32. G. R. M. Barcelos, D. Grotto, J. M. Serpeloni et al., "Bixin and norbixin protect against DNA-damage and alterations of redox status induced by methylmercury exposure in vivo," Environmental and Molecular Mutagenesis, vol. 53, no. 7, pp. 535-541, 2012.
33. B. E. Lee, Y. C. Hong, H. Park et al., "Interaction between GSTM1/GSTT1 polymorphism and blood mercury on birth weight," Environmental Health Perspectives, vol. 118, no. 3, pp. 437-443, 2010.
34. P. L. Sequetto, T. T. Oliveira, Í. A. C. Soares et al., "The flavonoid chrysin attenuates colorectal pathological remodeling reducing the number and severity of pre-neoplastic lesions in rats exposed to the carcinogen 1,2-dimethylhydrazine," Cell and Tissue Research, vol. 352, no. 2, pp. 327-339, 2013.
35. J. da Silva, T. R. O. de Freitas, V. Heuser, J. R. Marinho, and B. Erdtmann, "Genotoxicity biomonitoring in coal regions using wild rodent Ctenomys torquatus by comet assay and micronucleus test," Environmental and Molecular Mutagenesis, vol. 35, no. 4, pp. 270-278, 2000.
36. A. Hartmann, E. Agurell, C. Beevers et al., "Recommendations for conducting the in vivo alkaline comet assay," Mutagenesis, vol. 18, no. 1, pp. 45-51, 2003.
37. N. P. Singh, M. T. McCoy, R. R. Tice, and E. L. Schneider, "A simple technique for quantitation of low levels of DNA damage in individual cells," Experimental Cell Research, vol. 175, no. 1, pp. 184-191, 1988.
38. W. Strober, "Appendix 3B Trypan blue exclusion test of cell viability," Current Protocols in Immunology, 2001.
39. G. L. Ellman, "Tissue sulfhydryl groups," Archives of Biochemistry and Biophysics, vol. 82, no. 1, pp. 70-77, 1959.
40. 2, superoxide dismutase, and xanthine oxidase," Environmental and Molecular Mutagenesis, vol. 31, no. 4, pp. 352-361, 1998.
41. X. Jin, H. M. Chan, E. Lok et al., "Dietary fats modulate methylmercury-mediated systemic oxidative stress and oxidative DNA damage in rats," Food and Chemical Toxicology, vol. 46, no. 5, pp. 1706-1720, 2008.
42. F. A. Resende, W. Vilegas, L. C. Dos Santos, and E. A. Varanda, "Mutagenicity of flavonoids assayed by bacterial reverse mutation (Ames) test," Molecules, vol. 17, no. 5, pp. 5255-5268, 2012.
43. G. A. R. Oliveira, E. R. A. Ferraz, A. O Souza, R. A. Lourenço, D. P. Oliveira, and D. J. Dorta, "Evaluation of the mutagenic activity of chrysin, a flavonoid inhibitor of the aromatization process," journal of Toxicology and Environmental Health, Part A, vol. 75, no. 16-17, pp. 1000-1011, 2012.
44. D. Procházková, I. Boušová, and N. Wilhelmová, "Antioxidant and prooxidant properties of flavonoids," Fitoterapia, vol. 82, no. 4, pp. 513-523, 2011.
45. H. Y. Khan, H. Zubair, M. F. Ullah, A. Ahmad, and S. M. Hadi, "A prooxidant mechanism for the anticancer and chemopreventive properties of plant polyphenols," Current Drug Targets, vol. 13, no. 14, pp. 1738-1749, 2012.
46. N. J. Hewitt and P. Hewitt, "Phase I and II enzyme characterization of two sources of HepG2 cell lines," Xenobiotica, vol. 34, no. 3, pp. 243-256, 2004.
47. G. Reifferscheid and S. Buchinger, "Cell-based genotoxity testing," in Whole Cell Sensing System II, S. Belkin and M. B. Gu, Eds., pp. 113-156, Springer, 2012.
48. J. A. Timbrell and T. C. Marrs, "Biotransformation of xenobiotics," in General, Applied and Systems Toxicology, John Wiley & Sons, New York, NY, USA, 2009.
49. C. Chen, L. Qu, B. Li et al., "Increased oxidative DNA damage, as assessed by urinary 8-hydroxy-2/-deoxyguanosine concentrations, and serum redox status in persons exposed to mercury," Clinical Chemistry, vol. 51, no. 4, pp. 759-767, 2005.
50. D. Grotto, J. Valentini, M. Fillion et al., "Mercury exposure and oxidative stress in communities of the Brazilian Amazon," Science of the Total Environment, vol. 408, no. 4, pp. 806-811, 2010.
51. F. Schurz, M. Sabater-Vilar, and J. Fink-Gremmels, "Mutagenicity of mercury chloride and mechanisms of cellular defence: the role of metal-binding proteins," Mutagenesis, vol. 15, no. 6, pp. 525-530, 2000.
52. R. J. Singh, "Glutathione: a marker and antioxidant for aging," Journal of Laboratory and Clinical Medicine, vol. 140, no. 6, pp. 380-381, 2002.
53. T. A. Sarafian, "Methylmercury-induced generation of free radicals: biological implications," Metal ions in Biological Systems, vol. 36, pp. 415-444, 1999.
54. M. C. Houston, "The role of mercury and cadmium heavy metals in vascular disease, hypertension, coronary heart disease, and myocardial infarction," Alternative Therapies in Health and Medicine, vol. 13, no. 2, pp. S128-S133, 2007.
55. B. Halliwell and J. M. C. Gutteridge, Free Radicals in Biology and Medicine, Oxford University Press, London, UK, 1999.
56. S. Hussain, A. Atkinson, S. J. Thompson, and A. T. Khan, "Accumulation of mercury and its effect on antioxidant enzymes in brain, liver, and kidneys of mice," Journal of Environmental Science and Health-Part B Pesticides, Food Contaminants, and Agricultural Wastes, vol. 34, no. 4, pp. 645-660, 1999.
57. V. Breinholt, S. T. Lauridsen, and L. O. Dragsted, "Differential effects of dietary flavonoids on drug metabolizing and antioxidant enzymes in female rat," Xenobiotica, vol. 29, no. 12, pp. 1227-1240, 1999.
58. V. Benković, N. Orsolić, A. H. Knežević et al., "Evaluation of the radioprotective effects of propolis and flavonoids in gammairradiated mice: the alkaline comet assay study," Biological & Pharmaceutical Bulletin, vol. 31, no. 1, pp. 167-172, 2008.
59. V. Benković, A. H. Knežević, N. Orsolić et al., "Evaluation of radioprotective effects of propolis and its flavonoid constituents: in vitro study on human white blood cells," Phytotherapy Research, vol. 23, no. 8, pp. 1159-1168, 2009.
60. F. A. Resende, C. P. da Silva Almeida, W. Vilegas, and E. A. Varanda, "Differences in the hydroxylation pattern of flavonoids alter their chemoprotective effect against direct- and in direct-acting mutagens," Food Chemistry, vol. 155, pp. 251-255, 2014.
61. S. J. S. Flora, "Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure," Oxidative Medicine and Cellular Longevity, vol. 2, no. 4, pp. 191-206, 2009.
62. S. J. S. Flora and V. Pachauri, "Chelation in metal intoxication," Jnternational Journal of Environmental Research and Public Health, vol. 7, no. 7, pp. 2745-2788, 2010.
63. O. Ciftci, I. Ozdemir, N. Vardi, A. Beytur, and F. Oguz, "Ameliorating effects of quercetin and chrysin on 2,3,7,8-tetrachlorodi-benzo-P-dioxin-induced nephrotoxicity in rats," Toxicology and Industrial Health, vol. 28, no. 10, pp. 947-954, 2012.
64. O. Ciftci, N. Vardi, and I. Ozdemir, "Effects of quercetin and chrysin on 2,3,7,8-tetrachlorodibenzo-p-dioxin induced hepatotoxicity in rats," Environmental Toxicology, vol. 28, no. 3, pp. 146-154, 2013.
65. R. H. Liu, "Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals," The American journal of Clinical Nutrition, vol. 78, supplement 3, pp. S517-S520, 2003.
66. Y. J. Surh, "Cancer chemoprevention with dietary phytochemicals," Nature Reviews Cancer, vol. 3, no. 10, pp. 768-780, 2003.
67. T. M. de Kok, S. G. van Breda, and M. M. Manson, "Mechanisms of combined action of different chemopreventive dietary compounds: a review," European journal of Nutrition, vol. 47, supplement 2, pp. 51-59, 2008.
68. M.-T. Huang, R. L. Chang, A. W. Wood et al, "Inhibition of the mutagenicity of bay-region diol-epoxides of polycyclic aromatic hydrocarbons by tannic acid, hydroxylated anthraquinones and hydroxylated cinnamic acid derivatives," Carcinogenesis, vol. 6, no. 2, pp. 237-242, 1985.
69. G. R. M. Barcelos, J. P. F. Angeli, J. M. Serpeloni et al., "Quercetin protects human-derived liver cells against mercury-induced DNA-damage and alterations of the redox status," Mutation Research/Genetic Toxicology and Environmental Mutagenesis, vol. 726, no. 2, pp. 109-115, 2011.
70. J. M. Serpeloni, G. R. M. Barcelos, J. P. Friedmann Angeli, A. Z. Mercadante, M. Lourdes Pires Bianchi, and L. M. Greggi Antunes, "Dietary carotenoid lutein protects against DNA damage and alterations of the redox status induced by cisplatin in human derived HepG2 cells," Toxicology in Vitro, vol. 26, no. 2, pp. 288-294, 2012.
71. Z. Sahhugi, S. M. Hasenan, and Z. Jubri, "Protective effects of gelam honey against oxidative damage in young and aged rats," Oxidative Medicine and Cellular Longevity, vol. 2014, Article ID 673628, 8 pages, 2014.
72. E. Brown, N. S. Hurd, S. McCall, and T. E. Ceremuga, "Evaluation of the anxiolytic effects of chrysin, a Passiflora incarnata extract, in the laboratory rat," AANA journal, vol. 75, no. 5, pp. 333-337, 2007
73. S. K. Jaganathan and M. Mandai, "Antiproliferative effects of honey and of its polyphenols: a review," journal of Biomedicine and Biotechnology, vol. 2009, Article ID 830616, 13 pages, 2009.
74. P. Premratanachai and C. Chanchao, "Review of the anticancer activities of bee products," Asian Pacific journal of Tropical Biomedicine, vol. 4, no. 5, pp. 337-344, 2014.
75. J. Lachman, A. Hejtmánková, J. Sýkora, J. Karban, M. Orsák, and B. Rygerová, "Contents of major phenolic and flavonoid antioxidants in selected Czech honey," Czech journal of Food Sciences, vol. 28, no. 5, pp. 412-426, 2010.
76. M.-H. Siess, A.-M. Le Bon, M.-C. Canivenc-Lavier et al., "Flavonoids of honey and propolis: characterization and effects on hepatic drug-metabolizing enzymes and benzo[a]pyrene-DNA binding in rats," journal of Agricultural and Food Chemistry, vol. 44, no. 8, pp. 2297-2301, 1996.
77. M. Uhl, S. Ecker, F. Kassie et al., "Effect of chrysin, a flavonoid compound, on the mutagenic activity of 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and benzo(a)pyrene (B(a)P) in bacterial and human hepatoma (HepG2) cells," Archives of Toxicology, vol. 77, no. 8, pp. 477-484, 2003.
78. K. V. Anand, M. S. Mohamed Jaabir, P. A. Thomas, and P. Géraldine, "Protective role of chrysin against oxidative stress in d-galactose-induced aging in an experimental rat model," Geriatrics and Gerontology International, vol. 12, no. 4, pp. 741-750, 2012.
79. B. E. Milien and P. A. Quatromoni, "Nutritional research within the Framingham Heart Study," The journal of Nutrition Health and Aging, vol. 5, no. 3, pp. 139-143, 2001.
80. S. P. Whelton, J. He, P. K. Whelton, and P. Muntner, "Metaanalysis of observational studies on fish intake and coronary heart disease," The American journal of Cardiology, vol. 93, no. 9, pp. 1119-1123, 2004.
81. T. W. Clarkson, "The three modern faces of mercury," Environmental Health Perspectives, vol. 110, supplement 1, pp. 11-23, 2002.
82. T. W. Clarkson and L. Magos, "The toxicology of mercury and its chemical compounds," Critical Reviews in Toxicology, vol. 36, no. 8, pp. 609-662, 2006.
83. A. M. Visnjevec, D. Kocman, and M. Horvat, "Human mercury exposure and effects in Europe," Environmental Toxicology and Chemistry, vol. 33, no. 6, pp. 1259-1270, 2014.
84. H. M. Chan and G. M. Egeland, "Fish consumption, mercury exposure, and heart diseases," Nutrition Reviews, vol. 62, no. 2, pp. 68-72, 2004.
85. D. Grotto, J. Valentini, J. M. Serpeloni et al., "Evaluation of toxic effects of a diet containing fish contaminated with methylmercury in rats mimicking the exposure in the Amazon riverside population," Environmental Research, vol. 111, no. 8, pp. 1074-1082, 2011.
86. A. H. Stern, "A review of the studies of the cardiovascular health effects of methylmercury with consideration of their suitability for risk assessment," Environmental Research, vol. 98, no. 1, pp. 133-142, 2005.
87. S. A. Counter and L. H. Buchanan, "Mercury exposure in children: a review," Toxicology and Applied Pharmacology, vol. 198, no. 2, pp. 209-230, 2004.
88. C. Johansson, A. E Castoldi, N. Onishchenko, L. Manzo, M. Vahter, and S. Ceccatelli, "Neurobehavioural and molecular changes induced by methylmercury exposure during development," Neurotoxicity Research, vol. 11, no. 3-4, pp. 241-260, 2007
89. M. R. Karagas, A. L. Choi, E. Oken et al., "Evidence on the human health effects of low-level methylmercury exposure," Environmental Health Perspectives, vol. 120, no. 6, pp. 799-806, 2012.
90. A. L. Choi, P. Weihe, E. Budtz-Jørgensen et al., "Methylmercury exposure and adverse cardiovascular effects in Faroese whaling men," Environmental Health Perspectives, vol. 117, no. 3, pp. 367-372, 2009.
91. M. C. Houston, "Role of mercury toxicity in hypertension, cardiovascular disease, and stroke," The journal of Clinical Hypertension, vol. 13, no. 8, pp. 621-627, 2011.
92. M. Farina, M. Aschner, and J. B. T. Rocha, "Oxidative stress in MeHg-induced neurotoxicity," Toxicology and Applied Pharmacology, vol. 256, no. 3, pp. 405-417, 2011.
93. D. Joshi, M. D. Kumar, S. A. Kumar, and S. Sangeeta, "Reversal of methylmercury-induced oxidative stress, lipid peroxidation, and DNA damage by the treatment of N-acetyl cysteine: a protective approach," journal of Environmental Pathology, Toxicology and Oncology, vol. 33, no. 2, pp. 167-182, 2014.
94. C. J. S. Passos, D. S. da Silva, M. Lemire et al., "Daily mercury intake in fish-eating populations in the Brazilian Amazon," journal of Exposure Science and Environmental Epidemiology, vol. 18, no. 1, pp. 76-87, 2008.
95. G. R. M. Barcelos, D. Grotto, J. M. Serpeloni et al., "Protective properties of quercetin against DNA damage and oxidative stress induced by methylmercury in rats," Archives of Toxicology, vol. 85, no. 9, pp. 1151-1157, 2011.
96. G. R. M. Barcelos, D. Grotto, J. M. Serpeloni et al., "Bixin and norbixin protect against DNA-damage and alterations of redox status induced by methylmercury exposure in vivo," Environmental and Molecular Mutagenesis, vol. 53, no. 7, pp. 535-541, 2012.
97. B. E. Lee, Y. C. Hong, H. Park et al., "Interaction between GSTM1/GSTT1 polymorphism and blood mercury on birth weight," Environmental Health Perspectives, vol. 118, no. 3, pp. 437-443, 2010.
98. P. L. Sequetto, T. T. Oliveira, Í. A. C. Soares et al., "The flavonoid chrysin attenuates colorectal pathological remodeling reducing the number and severity of pre-neoplastic lesions in rats exposed to the carcinogen 1,2-dimethylhydrazine," Cell and Tissue Research, vol. 352, no. 2, pp. 327-339, 2013.
99. J. da Silva, T. R. O. de Freitas, V. Heuser, J. R. Marinho, and B. Erdtmann, "Genotoxicity biomonitoring in coal regions using wild rodent Ctenomys torquatus by comet assay and micronucleus test," Environmental and Molecular Mutagenesis, vol. 35, no. 4, pp. 270-278, 2000.
100. A. Hartmann, E. Agurell, C. Beevers et al., "Recommendations for conducting the in vivo alkaline comet assay," Mutagenesis, vol. 18, no. 1, pp. 45-51, 2003.
101. N. P. Singh, M. T. McCoy, R. R. Tice, and E. L. Schneider, "A simple technique for quantitation of low levels of DNA damage in individual cells," Experimental Cell Research, vol. 175, no. 1, pp. 184-191, 1988.
102. W. Strober, "Appendix 3B Trypan blue exclusion test of cell viability," Current Protocols in Immunology, 2001.
103. G. L. Ellman, "Tissue sulfhydryl groups," Archives of Biochemistry and Biophysics, vol. 82, no. 1, pp. 70-77, 1959.
104. 2, superoxide dismutase, and xanthine oxidase," Environmental and Molecular Mutagenesis, vol. 31, no. 4, pp. 352-361, 1998.
105. X. Jin, H. M. Chan, E. Lok et al., "Dietary fats modulate methylmercury-mediated systemic oxidative stress and oxidative DNA damage in rats," Food and Chemical Toxicology, vol. 46, no. 5, pp. 1706-1720, 2008.
106. F. A. Resende, W. Vilegas, L. C. Dos Santos, and E. A. Varanda, "Mutagenicity of flavonoids assayed by bacterial reverse mutation (Ames) test," Molecules, vol. 17, no. 5, pp. 5255-5268, 2012.
107. G. A. R. Oliveira, E. R. A. Ferraz, A. O Souza, R. A. Lourenço, D. P. Oliveira, and D. J. Dorta, "Evaluation of the mutagenic activity of chrysin, a flavonoid inhibitor of the aromatization process," journal of Toxicology and Environmental Health, Part A, vol. 75, no. 16-17, pp. 1000-1011, 2012.
108. D. Procházková, I. Boušová, and N. Wilhelmová, "Antioxidant and prooxidant properties of flavonoids," Fitoterapia, vol. 82, no. 4, pp. 513-523, 2011.
109. H. Y. Khan, H. Zubair, M. F. Ullah, A. Ahmad, and S. M. Hadi, "A prooxidant mechanism for the anticancer and chemopreventive properties of plant polyphenols," Current Drug Targets, vol. 13, no. 14, pp. 1738-1749, 2012.
110. N. J. Hewitt and P. Hewitt, "Phase I and II enzyme characterization of two sources of HepG2 cell lines," Xenobiotica, vol. 34, no. 3, pp. 243-256, 2004.
111. G. Reifferscheid and S. Buchinger, "Cell-based genotoxity testing," in Whole Cell Sensing System II, S. Belkin and M. B. Gu, Eds., pp. 113-156, Springer, 2012.
112. J. A. Timbrell and T. C. Marrs, "Biotransformation of xenobiotics," in General, Applied and Systems Toxicology, John Wiley & Sons, New York, NY, USA, 2009.
113. C. Chen, L. Qu, B. Li et al., "Increased oxidative DNA damage, as assessed by urinary 8-hydroxy-2/-deoxyguanosine concentrations, and serum redox status in persons exposed to mercury," Clinical Chemistry, vol. 51, no. 4, pp. 759-767, 2005.
114. D. Grotto, J. Valentini, M. Fillion et al., "Mercury exposure and oxidative stress in communities of the Brazilian Amazon," Science of the Total Environment, vol. 408, no. 4, pp. 806-811, 2010.
115. F. Schurz, M. Sabater-Vilar, and J. Fink-Gremmels, "Mutagenicity of mercury chloride and mechanisms of cellular defence: the role of metal-binding proteins," Mutagenesis, vol. 15, no. 6, pp. 525-530, 2000.
116. R. J. Singh, "Glutathione: a marker and antioxidant for aging," Journal of Laboratory and Clinical Medicine, vol. 140, no. 6, pp. 380-381, 2002.
117. T. A. Sarafian, "Methylmercury-induced generation of free radicals: biological implications," Metal ions in Biological Systems, vol. 36, pp. 415-444, 1999.
118. M. C. Houston, "The role of mercury and cadmium heavy metals in vascular disease, hypertension, coronary heart disease, and myocardial infarction," Alternative Therapies in Health and Medicine, vol. 13, no. 2, pp. S128-S133, 2007.
119. B. Halliwell and J. M. C. Gutteridge, Free Radicals in Biology and Medicine, Oxford University Press, London, UK, 1999.
120. S. Hussain, A. Atkinson, S. J. Thompson, and A. T. Khan, "Accumulation of mercury and its effect on antioxidant enzymes in brain, liver, and kidneys of mice," Journal of Environmental Science and Health-Part B Pesticides, Food Contaminants, and Agricultural Wastes, vol. 34, no. 4, pp. 645-660, 1999.
121. V. Breinholt, S. T. Lauridsen, and L. O. Dragsted, "Differential effects of dietary flavonoids on drug metabolizing and antioxidant enzymes in female rat," Xenobiotica, vol. 29, no. 12, pp. 1227-1240, 1999.
122. V. Benković, N. Orsolić, A. H. Knežević et al., "Evaluation of the radioprotective effects of propolis and flavonoids in gammairradiated mice: the alkaline comet assay study," Biological & Pharmaceutical Bulletin, vol. 31, no. 1, pp. 167-172, 2008.
123. V. Benković, A. H. Knežević, N. Orsolić et al., "Evaluation of radioprotective effects of propolis and its flavonoid constituents: in vitro study on human white blood cells," Phytotherapy Research, vol. 23, no. 8, pp. 1159-1168, 2009.
124. F. A. Resende, C. P. da Silva Almeida, W. Vilegas, and E. A. Varanda, "Differences in the hydroxylation pattern of flavonoids alter their chemoprotective effect against direct- and in direct-acting mutagens," Food Chemistry, vol. 155, pp. 251-255, 2014.
125. S. J. S. Flora, "Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure," Oxidative Medicine and Cellular Longevity, vol. 2, no. 4, pp. 191-206, 2009.
126. S. J. S. Flora and V. Pachauri, "Chelation in metal intoxication," Jnternational Journal of Environmental Research and Public Health, vol. 7, no. 7, pp. 2745-2788, 2010.
127. O. Ciftci, I. Ozdemir, N. Vardi, A. Beytur, and F. Oguz, "Ameliorating effects of quercetin and chrysin on 2,3,7,8-tetrachlorodi-benzo-P-dioxin-induced nephrotoxicity in rats," Toxicology and Industrial Health, vol. 28, no. 10, pp. 947-954, 2012.
128. O. Ciftci, N. Vardi, and I. Ozdemir, "Effects of quercetin and chrysin on 2,3,7,8-tetrachlorodibenzo-p-dioxin induced hepatotoxicity in rats," Environmental Toxicology, vol. 28, no. 3, pp. 146-154, 2013.