Mangiferin: A xanthone attenuates mercury chloride induced cytotoxicity and genotoxicity in HepG2 cells

A xanthone attenuates mercury chloride induced cytotoxicity and genotoxicity in HepG2 cells

Mudholkar Kaivalya, B. Nageshwar Rao, B. S. Satish Rao

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Mangiferin (MGN), a dietary C-glucosylxanthone present in Mangifera indica, is known to possess a spectrum of beneficial pharmacological properties. This study demonstrates antigenotoxic potential of MGN against mercuric chloride (HgCl2) induced genotoxicity in HepG2 cell line. Treatment of HepG2 cells with various concentrations of HgCl2 for 3 h caused a dose-dependent increase in micronuclei frequency and elevation in DNA strand breaks (olive tail moment and tail DNA). Pretreatment with MGN significantly (p < 0.01) inhibited HgCl2-induced (20 μM for 30 h) DNA damage. An optimal antigenotoxic effect of MGN, both in micronuclei and comet assay, was observed at a concentration of 50 μM. Furthermore, HepG2 cells treated with various concentrations of HgCl2 resulted in a dose-dependent increase in the dichlorofluorescein fluorescence, indicating an increase in the generation of reactive oxygen species (ROS). However, MGN by itself failed to generate ROS at a concentration of 50 μM, whereas it could significantly decrease HgCl2-induced ROS. Our study clearly demonstrates that MGN pretreatment reduced the HgCl2-induced DNA damage in HepG2 cells, thus demonstrating the genoprotective potential of MGN, which is mediated mainly by the inhibition of oxidative stress.

Original languageEnglish
Pages (from-to)108-116
Number of pages9
JournalJournal of Biochemical and Molecular Toxicology
Volume25
Issue number2
DOIs
Publication statusPublished - 03-2011

Fingerprint

Mercuric Chloride
Hep G2 Cells
Cytotoxicity
Mercury
Chlorides
Reactive Oxygen Species
DNA
DNA Damage
Mangifera
Micronucleus Tests
DNA Breaks
Oxidative stress
Comet Assay
Olea
mangiferin
xanthone
Assays
Oxidative Stress
Fluorescence
Cells

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

@article{60667a435e92421c9ae3f6068ad9c02b,
title = "Mangiferin: A xanthone attenuates mercury chloride induced cytotoxicity and genotoxicity in HepG2 cells: A xanthone attenuates mercury chloride induced cytotoxicity and genotoxicity in HepG2 cells",
abstract = "Mangiferin (MGN), a dietary C-glucosylxanthone present in Mangifera indica, is known to possess a spectrum of beneficial pharmacological properties. This study demonstrates antigenotoxic potential of MGN against mercuric chloride (HgCl2) induced genotoxicity in HepG2 cell line. Treatment of HepG2 cells with various concentrations of HgCl2 for 3 h caused a dose-dependent increase in micronuclei frequency and elevation in DNA strand breaks (olive tail moment and tail DNA). Pretreatment with MGN significantly (p < 0.01) inhibited HgCl2-induced (20 μM for 30 h) DNA damage. An optimal antigenotoxic effect of MGN, both in micronuclei and comet assay, was observed at a concentration of 50 μM. Furthermore, HepG2 cells treated with various concentrations of HgCl2 resulted in a dose-dependent increase in the dichlorofluorescein fluorescence, indicating an increase in the generation of reactive oxygen species (ROS). However, MGN by itself failed to generate ROS at a concentration of 50 μM, whereas it could significantly decrease HgCl2-induced ROS. Our study clearly demonstrates that MGN pretreatment reduced the HgCl2-induced DNA damage in HepG2 cells, thus demonstrating the genoprotective potential of MGN, which is mediated mainly by the inhibition of oxidative stress.",
author = "Mudholkar Kaivalya and Rao, {B. Nageshwar} and {Satish Rao}, {B. S.}",
note = "Cited By :10 Export Date: 11 November 2017 CODEN: JBMTF Correspondence Address: Satish Rao, B.S.; Division of Radiobiology and Toxicology, Manipal Life Sciences Centre, Manipal University, Manipal 576 104, India; email: satishraomlsc@gmail.com Chemicals/CAS: dichlorofluorescein, 18362-80-6, 2320-96-9, 26836-01-1, 76-54-0, 81-87-8; mangiferin, 4773-96-0; mercury chloride, 51312-24-4; Mercuric Chloride, 7487-94-7; Reactive Oxygen Species; Xanthones; mangiferin, 4773-96-0; xanthone, 90-47-1 Manufacturers: Sigma References: Bridges, C.C., Zalups, R.K., Molecular and ionic mimicry and the transport of toxic metals (2005) Toxicol Appl Pharmacol, 204, pp. 274-308; Baird, C., Cann, M., (2004) Environmental chemistry, , New York: W. H. Freeman and Co; Bolger, P.M., Schwetz, B.A., Mercury and health (2002) N Engl J Med, 347, pp. 1735-1736; Ekino, S., Susa, M., Ninomiya, T., Imamura, K., Kitamura, T., Minamata disease revisited: an update on the acute and chronic manifestations of methyl mercury poisoning (2007) J Neurol Sci, 262, pp. 131-144; Tchounwou, P.B., Ayensu, W.K., Ninashvili, N., Sutton, D., Environmental exposure to mercury and its toxicopathologic implications for public health (2003) Environ Toxicol, 18, pp. 149-175; Boffetta, P., Merler, E., Vainio, H., Carcinogenicity of mercury and mercury compounds (1993) Scand J Work Environ Health, 19, pp. 1-7; Clarkson, T.W., Magos, L., Myers, G.J., The toxicology of mercury-current exposures and clinical manifestations (2003) N Engl J Med, 349, pp. 1731-1737; Leonard, A., Jacquet, P., Lauwerys, R.R., Mutagenicity and teratogenicity of mercury compounds (1983) Mutat Res, 114, pp. 1-18; Cebulska-Wasilewska, A., Panek, A., Zabinski, Z., Moszczynski, P., Au, W.W., Occupational exposure to mercury vapour on genotoxicity and DNA repair (2005) Mutat Res, 586, pp. 102-114; Janicki, K., Dobrowolski, J., Krasnicki, K., Correlation between contamination of the rural environment with mercury and occurrence of leukaemia in men and cattle (1987) Chemosphere, 16, pp. 253-257; Beryllium, cadmium, mercury and exposures in the glass manufacturing industry (1993) Monogr Eval Carcinog Risks Hum IARC, 58, pp. 119-238. , IARC; Devasagayam, T.P., Tilak, J.C., Boloor, K.K., Sane, K.S., Ghaskadbi, S.S., Lele, R.D., Free radicals and antioxidants in human health: Current status and future prospects (2004) J Assoc Physicians India, 52, pp. 794-804; Roberts, J.C., Naturally occurring xanthones (2002) Chem Rev, 61, pp. 591-605; Pardo-Andreu, G.L., Paim, B.A., Castilho, R.F., Velho, J.A., Delgado, R., Vercesi, A.E., Oliveira, H.C., Mangifera indica L. extract (Vimang) and its main polyphenol mangiferin prevent mitochondrial oxidative stress in atherosclerosis-prone hypercholesterolemic mouse (2008) Pharmacol Res, 57, pp. 332-338; Amazzal, L., Lapotre, A., Quignon, F., Bagrel, D., Mangiferin protects against 1-methyl-4-phenylpyridinium toxicity mediated by oxidative stress in N2A cells (2007) Neurosci Lett, 418, pp. 159-164; Martin, M., Qian, H., Major mango polyphenols and their potential significance to human health (2008) Compr Rev Food Sci Food Saf, 7, pp. 309-319; Satish Rao, B.S., Sreedevi, M.V., Nageshwar Rao, B., Cytoprotective and antigenotoxic potential of Mangiferin, a glucosylxanthone against cadmium chloride induced toxicity in HepG2 cells (2009) Food Chem Toxicol, 47, pp. 592-600; Sundermann, M.V., Knasm{\"u}ller, S., Wu, X.J., Darroudi, F., Kassie, F., Use of a human-derived liver cell line for the detection of cytoprotective, antigenotoxic and cogenotoxic agents (2004) Toxicology, 198, pp. 329-340; Mossman, B.T., In vitro approaches for determining mechanisms of toxicity and carcinogenicity by asbestos in the gastrointestinal and respiratory tracts (1983) Environ Health Perspect, 53, pp. 155-161; Fenech, M., Morley, A.A., Measurement of micronuclei in lymphocytes (1985) Mutat Res, 147, pp. 29-36; Rao, B.S., Shanbhoge, R., Upadhya, D., Jagetia, G.C., Adiga, S.K., Kumar, P., Guruprasad, K., Gayathri, P., Antioxidant, anticlastogenic and radioprotective effect of Coleus aromaticus on Chinese hamster fibroblast cells (V79) exposed to gamma radiation (2006) Mutagenesis, 21, pp. 237-242; Fenech, M., Chang, W.P., Kirsch-Volders, M., Holland, N., Bonassi, S., Zeiger, E., HUMN project: detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures (2003) Mutat Res, 534, pp. 65-75; Surralles, J., Xamena, N., Creus, A., Marcos, R., The suitability of the micronucleus assay in human lymphocytes as a new biomarker of excision repair (1995) Mutat Res, 342, pp. 43-59; Singh, N.P., McCoy, M.T., Tice, R.R., Schneider, E.L., A simple technique for quantitation of low levels of DNA damage in individual cells (1988) Exp Cell Res, 175, pp. 184-191; Collins, A., Dusinska, M., Franklin, M., Somorovska, M., Petrovska, H., Duthie, S., Fillion, L., Vaughan, N., Comet assay in human biomonitoring studies: reliability, validation, and applications (1997) Environ Mol Mutagen, 30, pp. 139-146; Bai, J., Cederbaum, A.I., Catalase protects HepG2 cells from apoptosis induced by DNA-damaging agents by accelerating the degradation of p53 (2003) J Biol Chem, 278, pp. 4660-4667; Erich, G., Mutagenicity, carcinogenicity, and teratogenicity (2008) Merian editor. Elements and their compounds in the environment, pp. 433-457. , In:, 2nd edition. WILEY-VCH, Weinheim, Germany; Cantoni, O., Christie, N.T., Swann, A., Drath, D.B., Costa, M., Mechanism of HgCl2 cytotoxicity in cultured mammalian cells (1984) Mol Pharmacol, 26, pp. 360-368; De Flora, S., Bennicelli, C., Bagnasco, M., Genotoxicity of mercury compounds (1994) A review. Mutat Res, 317, pp. 57-79; Silva-Pereira, L.C., Cardoso, P.C., Leite, D.S., Bahia, M.O., Bastos, W.R., Smith, M.A., Burbano, R.R., Cytotoxicity and genotoxicity of low doses of mercury chloride and methylmercury chloride on human lymphocytes in vitro (2005) Braz J Med Biol Res, 38, pp. 901-907; Crespo-Lopez, M.E., Macedo, G.L., Pereira, S.I., Arrifano, G.P., Picanco-Diniz, D.L., do Nascimento, J.L., Herculano, A.M., Mercury and human genotoxicity: critical considerations and possible molecular mechanisms (2009) Pharmacol Res, 60, pp. 212-220; Guzzi, G., La Porta, C.A., Molecular mechanisms triggered by mercury (2008) Toxicology, 244, pp. 1-12; Hartwig, A., Carcinogenicity of metal compounds: possible role of DNA repair inhibition (1998) Toxicol Lett, 102-103, pp. 235-239; Thier, R., Bonacker, D., Stoiber, T., Bohm, K.J., Wang, M., Unger, E., Bolt, H.M., Degen, G., Interaction of metal salts with cytoskeletal motor protein systems (2003) Toxicol Lett, 140-141, pp. 75-81; Burton, C.A., Hatlelid, K., Divine, K., Carter, D.E., Fernando, Q., Brendel, K., Gandolfi, A.J., Glutathione effects on toxicity and uptake of mercuric chloride and sodium arsenite in rabbit renal cortical slices (1995) Environ Health Perspect, 103, pp. 81-84; Sahu, S.C., Gray, G.C., Pro-oxidant activity of flavonoids: effects on glutathione and glutathione S-transferase in isolated rat liver nuclei (1996) Cancer Lett, 104, pp. 193-196; Shih, C.M., Lin, H., Liang, Y.C., Lee, W.S., Bi, W.F., Juan, S.H., Concentration-dependent differential effects of quercetin on rat aortic smooth muscle cells (2004) Eur J Pharmacol, 496, pp. 41-48; Stopper, H., M{\"u}ller, S.O., Micronuclei as a biological endpoint for genotoxicity: A minireview (1997) Toxicol in Vitro, 11, pp. 661-667; Andersen, O., Ronne, M., Nordberg, G.F., Effects of inorganic metal salts on chromosome length in human lymphocytes (1983) Hereditas, 98, pp. 65-70; Rossmann, T., (1995) Metal mutagenesis. In Toxicology of metals: Biochemical aspects, pp. 373-406. , Berlin: Springer-Verlag; Amorim, M.I., Mergler, D., Bahia, M.O., Dubeau, H., Miranda, D., Lebel, J., Burbano, R.R., Lucotte, M., Cytogenetic damage related to low levels of methyl mercury contamination in the Brazilian Amazon (2000) An Acad Bras Cienc, 72, pp. 497-507; Betti, C., Davini, T., He, J., Barale, R., Liquid holding effects on methylmercury genotoxicity in human lymphocytes (1993) Mutat Res, 301, pp. 267-273; Fenech, M., Rinaldi, J., Surralles, J., The origin of micronuclei induced by cytosine arabinoside and its synergistic interaction with hydroxyurea in human lymphocytes (1994) Mutagenesis, 9, pp. 273-277; Sobhika, A., Nageshwar Rao, B., Kaivalya, M., Ridhirama, B., Satish Rao, B.S., Mangiferin, a dietary xanthone protects against mercury-induced toxicity in HepG2 cells. Environ Toxicol (DOI 10.1002/tox.20620); Kasi Viswanadh, E., Nageshwar Rao, B., Satish Rao, B.S., Antigenotoxic effect of mangiferin and changes in antioxidant enzyme levels of Swiss albino mice treated with cadmium chloride (2010) Hum Exp Toxicol, 29, pp. 409-418; Sato, T., Kawamoto, A., Tamura, A., Tatsumi, Y., Fujii, T., Mechanism of antioxidant action of pueraria glycoside (PG)-1 (an isoflavonoid) and mangiferin (a xanthonoid) (1992) Chem Pharm Bull (Tokyo), 40, pp. 721-724",
year = "2011",
month = "3",
doi = "10.1002/jbt.20366",
language = "English",
volume = "25",
pages = "108--116",
journal = "Journal of Biochemical and Molecular Toxicology",
issn = "1095-6670",
publisher = "John Wiley and Sons Inc.",
number = "2",

}

TY - JOUR

T1 - Mangiferin: A xanthone attenuates mercury chloride induced cytotoxicity and genotoxicity in HepG2 cells

T2 - A xanthone attenuates mercury chloride induced cytotoxicity and genotoxicity in HepG2 cells

AU - Kaivalya, Mudholkar

AU - Rao, B. Nageshwar

AU - Satish Rao, B. S.

N1 - Cited By :10 Export Date: 11 November 2017 CODEN: JBMTF Correspondence Address: Satish Rao, B.S.; Division of Radiobiology and Toxicology, Manipal Life Sciences Centre, Manipal University, Manipal 576 104, India; email: satishraomlsc@gmail.com Chemicals/CAS: dichlorofluorescein, 18362-80-6, 2320-96-9, 26836-01-1, 76-54-0, 81-87-8; mangiferin, 4773-96-0; mercury chloride, 51312-24-4; Mercuric Chloride, 7487-94-7; Reactive Oxygen Species; Xanthones; mangiferin, 4773-96-0; xanthone, 90-47-1 Manufacturers: Sigma References: Bridges, C.C., Zalups, R.K., Molecular and ionic mimicry and the transport of toxic metals (2005) Toxicol Appl Pharmacol, 204, pp. 274-308; Baird, C., Cann, M., (2004) Environmental chemistry, , New York: W. H. Freeman and Co; Bolger, P.M., Schwetz, B.A., Mercury and health (2002) N Engl J Med, 347, pp. 1735-1736; Ekino, S., Susa, M., Ninomiya, T., Imamura, K., Kitamura, T., Minamata disease revisited: an update on the acute and chronic manifestations of methyl mercury poisoning (2007) J Neurol Sci, 262, pp. 131-144; Tchounwou, P.B., Ayensu, W.K., Ninashvili, N., Sutton, D., Environmental exposure to mercury and its toxicopathologic implications for public health (2003) Environ Toxicol, 18, pp. 149-175; Boffetta, P., Merler, E., Vainio, H., Carcinogenicity of mercury and mercury compounds (1993) Scand J Work Environ Health, 19, pp. 1-7; Clarkson, T.W., Magos, L., Myers, G.J., The toxicology of mercury-current exposures and clinical manifestations (2003) N Engl J Med, 349, pp. 1731-1737; Leonard, A., Jacquet, P., Lauwerys, R.R., Mutagenicity and teratogenicity of mercury compounds (1983) Mutat Res, 114, pp. 1-18; Cebulska-Wasilewska, A., Panek, A., Zabinski, Z., Moszczynski, P., Au, W.W., Occupational exposure to mercury vapour on genotoxicity and DNA repair (2005) Mutat Res, 586, pp. 102-114; Janicki, K., Dobrowolski, J., Krasnicki, K., Correlation between contamination of the rural environment with mercury and occurrence of leukaemia in men and cattle (1987) Chemosphere, 16, pp. 253-257; Beryllium, cadmium, mercury and exposures in the glass manufacturing industry (1993) Monogr Eval Carcinog Risks Hum IARC, 58, pp. 119-238. , IARC; Devasagayam, T.P., Tilak, J.C., Boloor, K.K., Sane, K.S., Ghaskadbi, S.S., Lele, R.D., Free radicals and antioxidants in human health: Current status and future prospects (2004) J Assoc Physicians India, 52, pp. 794-804; Roberts, J.C., Naturally occurring xanthones (2002) Chem Rev, 61, pp. 591-605; Pardo-Andreu, G.L., Paim, B.A., Castilho, R.F., Velho, J.A., Delgado, R., Vercesi, A.E., Oliveira, H.C., Mangifera indica L. extract (Vimang) and its main polyphenol mangiferin prevent mitochondrial oxidative stress in atherosclerosis-prone hypercholesterolemic mouse (2008) Pharmacol Res, 57, pp. 332-338; Amazzal, L., Lapotre, A., Quignon, F., Bagrel, D., Mangiferin protects against 1-methyl-4-phenylpyridinium toxicity mediated by oxidative stress in N2A cells (2007) Neurosci Lett, 418, pp. 159-164; Martin, M., Qian, H., Major mango polyphenols and their potential significance to human health (2008) Compr Rev Food Sci Food Saf, 7, pp. 309-319; Satish Rao, B.S., Sreedevi, M.V., Nageshwar Rao, B., Cytoprotective and antigenotoxic potential of Mangiferin, a glucosylxanthone against cadmium chloride induced toxicity in HepG2 cells (2009) Food Chem Toxicol, 47, pp. 592-600; Sundermann, M.V., Knasmüller, S., Wu, X.J., Darroudi, F., Kassie, F., Use of a human-derived liver cell line for the detection of cytoprotective, antigenotoxic and cogenotoxic agents (2004) Toxicology, 198, pp. 329-340; Mossman, B.T., In vitro approaches for determining mechanisms of toxicity and carcinogenicity by asbestos in the gastrointestinal and respiratory tracts (1983) Environ Health Perspect, 53, pp. 155-161; Fenech, M., Morley, A.A., Measurement of micronuclei in lymphocytes (1985) Mutat Res, 147, pp. 29-36; Rao, B.S., Shanbhoge, R., Upadhya, D., Jagetia, G.C., Adiga, S.K., Kumar, P., Guruprasad, K., Gayathri, P., Antioxidant, anticlastogenic and radioprotective effect of Coleus aromaticus on Chinese hamster fibroblast cells (V79) exposed to gamma radiation (2006) Mutagenesis, 21, pp. 237-242; Fenech, M., Chang, W.P., Kirsch-Volders, M., Holland, N., Bonassi, S., Zeiger, E., HUMN project: detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures (2003) Mutat Res, 534, pp. 65-75; Surralles, J., Xamena, N., Creus, A., Marcos, R., The suitability of the micronucleus assay in human lymphocytes as a new biomarker of excision repair (1995) Mutat Res, 342, pp. 43-59; Singh, N.P., McCoy, M.T., Tice, R.R., Schneider, E.L., A simple technique for quantitation of low levels of DNA damage in individual cells (1988) Exp Cell Res, 175, pp. 184-191; Collins, A., Dusinska, M., Franklin, M., Somorovska, M., Petrovska, H., Duthie, S., Fillion, L., Vaughan, N., Comet assay in human biomonitoring studies: reliability, validation, and applications (1997) Environ Mol Mutagen, 30, pp. 139-146; Bai, J., Cederbaum, A.I., Catalase protects HepG2 cells from apoptosis induced by DNA-damaging agents by accelerating the degradation of p53 (2003) J Biol Chem, 278, pp. 4660-4667; Erich, G., Mutagenicity, carcinogenicity, and teratogenicity (2008) Merian editor. Elements and their compounds in the environment, pp. 433-457. , In:, 2nd edition. WILEY-VCH, Weinheim, Germany; Cantoni, O., Christie, N.T., Swann, A., Drath, D.B., Costa, M., Mechanism of HgCl2 cytotoxicity in cultured mammalian cells (1984) Mol Pharmacol, 26, pp. 360-368; De Flora, S., Bennicelli, C., Bagnasco, M., Genotoxicity of mercury compounds (1994) A review. Mutat Res, 317, pp. 57-79; Silva-Pereira, L.C., Cardoso, P.C., Leite, D.S., Bahia, M.O., Bastos, W.R., Smith, M.A., Burbano, R.R., Cytotoxicity and genotoxicity of low doses of mercury chloride and methylmercury chloride on human lymphocytes in vitro (2005) Braz J Med Biol Res, 38, pp. 901-907; Crespo-Lopez, M.E., Macedo, G.L., Pereira, S.I., Arrifano, G.P., Picanco-Diniz, D.L., do Nascimento, J.L., Herculano, A.M., Mercury and human genotoxicity: critical considerations and possible molecular mechanisms (2009) Pharmacol Res, 60, pp. 212-220; Guzzi, G., La Porta, C.A., Molecular mechanisms triggered by mercury (2008) Toxicology, 244, pp. 1-12; Hartwig, A., Carcinogenicity of metal compounds: possible role of DNA repair inhibition (1998) Toxicol Lett, 102-103, pp. 235-239; Thier, R., Bonacker, D., Stoiber, T., Bohm, K.J., Wang, M., Unger, E., Bolt, H.M., Degen, G., Interaction of metal salts with cytoskeletal motor protein systems (2003) Toxicol Lett, 140-141, pp. 75-81; Burton, C.A., Hatlelid, K., Divine, K., Carter, D.E., Fernando, Q., Brendel, K., Gandolfi, A.J., Glutathione effects on toxicity and uptake of mercuric chloride and sodium arsenite in rabbit renal cortical slices (1995) Environ Health Perspect, 103, pp. 81-84; Sahu, S.C., Gray, G.C., Pro-oxidant activity of flavonoids: effects on glutathione and glutathione S-transferase in isolated rat liver nuclei (1996) Cancer Lett, 104, pp. 193-196; Shih, C.M., Lin, H., Liang, Y.C., Lee, W.S., Bi, W.F., Juan, S.H., Concentration-dependent differential effects of quercetin on rat aortic smooth muscle cells (2004) Eur J Pharmacol, 496, pp. 41-48; Stopper, H., Müller, S.O., Micronuclei as a biological endpoint for genotoxicity: A minireview (1997) Toxicol in Vitro, 11, pp. 661-667; Andersen, O., Ronne, M., Nordberg, G.F., Effects of inorganic metal salts on chromosome length in human lymphocytes (1983) Hereditas, 98, pp. 65-70; Rossmann, T., (1995) Metal mutagenesis. In Toxicology of metals: Biochemical aspects, pp. 373-406. , Berlin: Springer-Verlag; Amorim, M.I., Mergler, D., Bahia, M.O., Dubeau, H., Miranda, D., Lebel, J., Burbano, R.R., Lucotte, M., Cytogenetic damage related to low levels of methyl mercury contamination in the Brazilian Amazon (2000) An Acad Bras Cienc, 72, pp. 497-507; Betti, C., Davini, T., He, J., Barale, R., Liquid holding effects on methylmercury genotoxicity in human lymphocytes (1993) Mutat Res, 301, pp. 267-273; Fenech, M., Rinaldi, J., Surralles, J., The origin of micronuclei induced by cytosine arabinoside and its synergistic interaction with hydroxyurea in human lymphocytes (1994) Mutagenesis, 9, pp. 273-277; Sobhika, A., Nageshwar Rao, B., Kaivalya, M., Ridhirama, B., Satish Rao, B.S., Mangiferin, a dietary xanthone protects against mercury-induced toxicity in HepG2 cells. Environ Toxicol (DOI 10.1002/tox.20620); Kasi Viswanadh, E., Nageshwar Rao, B., Satish Rao, B.S., Antigenotoxic effect of mangiferin and changes in antioxidant enzyme levels of Swiss albino mice treated with cadmium chloride (2010) Hum Exp Toxicol, 29, pp. 409-418; Sato, T., Kawamoto, A., Tamura, A., Tatsumi, Y., Fujii, T., Mechanism of antioxidant action of pueraria glycoside (PG)-1 (an isoflavonoid) and mangiferin (a xanthonoid) (1992) Chem Pharm Bull (Tokyo), 40, pp. 721-724

PY - 2011/3

Y1 - 2011/3

N2 - Mangiferin (MGN), a dietary C-glucosylxanthone present in Mangifera indica, is known to possess a spectrum of beneficial pharmacological properties. This study demonstrates antigenotoxic potential of MGN against mercuric chloride (HgCl2) induced genotoxicity in HepG2 cell line. Treatment of HepG2 cells with various concentrations of HgCl2 for 3 h caused a dose-dependent increase in micronuclei frequency and elevation in DNA strand breaks (olive tail moment and tail DNA). Pretreatment with MGN significantly (p < 0.01) inhibited HgCl2-induced (20 μM for 30 h) DNA damage. An optimal antigenotoxic effect of MGN, both in micronuclei and comet assay, was observed at a concentration of 50 μM. Furthermore, HepG2 cells treated with various concentrations of HgCl2 resulted in a dose-dependent increase in the dichlorofluorescein fluorescence, indicating an increase in the generation of reactive oxygen species (ROS). However, MGN by itself failed to generate ROS at a concentration of 50 μM, whereas it could significantly decrease HgCl2-induced ROS. Our study clearly demonstrates that MGN pretreatment reduced the HgCl2-induced DNA damage in HepG2 cells, thus demonstrating the genoprotective potential of MGN, which is mediated mainly by the inhibition of oxidative stress.

AB - Mangiferin (MGN), a dietary C-glucosylxanthone present in Mangifera indica, is known to possess a spectrum of beneficial pharmacological properties. This study demonstrates antigenotoxic potential of MGN against mercuric chloride (HgCl2) induced genotoxicity in HepG2 cell line. Treatment of HepG2 cells with various concentrations of HgCl2 for 3 h caused a dose-dependent increase in micronuclei frequency and elevation in DNA strand breaks (olive tail moment and tail DNA). Pretreatment with MGN significantly (p < 0.01) inhibited HgCl2-induced (20 μM for 30 h) DNA damage. An optimal antigenotoxic effect of MGN, both in micronuclei and comet assay, was observed at a concentration of 50 μM. Furthermore, HepG2 cells treated with various concentrations of HgCl2 resulted in a dose-dependent increase in the dichlorofluorescein fluorescence, indicating an increase in the generation of reactive oxygen species (ROS). However, MGN by itself failed to generate ROS at a concentration of 50 μM, whereas it could significantly decrease HgCl2-induced ROS. Our study clearly demonstrates that MGN pretreatment reduced the HgCl2-induced DNA damage in HepG2 cells, thus demonstrating the genoprotective potential of MGN, which is mediated mainly by the inhibition of oxidative stress.

UR - http://www.scopus.com/inward/record.url?scp=79953709130&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953709130&partnerID=8YFLogxK

U2 - 10.1002/jbt.20366

DO - 10.1002/jbt.20366

M3 - Article

VL - 25

SP - 108

EP - 116

JO - Journal of Biochemical and Molecular Toxicology

JF - Journal of Biochemical and Molecular Toxicology

SN - 1095-6670

IS - 2

ER -