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References
Contents
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[1]ED Weinberg: The hazards of iron loading. Metallomics 2(11), 732-40 (2010).
[2]B Halliwell, JMC Gutteridge: Role of free radicals and catalytic metal ions in human diseases: An overview. Methods Enzymol 186, 1-86 (1990)
[3]HC Greenspan, OI Aruoma: Oxidative stress and apoptosis in HIV infection: a role for plant-derived metabolites with synergistic antioxidant activity. Immunol Today 15, 209-213 (1994)
[4]W Bors, W Heller, C Michel Saran: Flavonoids as antioxidants: determination of radical-scavenging efficiencies. Methods Enzymol. 186, 343-355 (1990)
[5]ME Inal, A Kahraman: The protective effect of flavonol quercetin against ultraviolet a induced oxidative stress in rats. Toxicology 154, 21-29 (2000)
[6]MJ Laughton, PJ Evans, MA Moroney, JR Hoult, B Halliwell:Biochem Pharmacol 48, 1673-1680 (1991)
[7]T Decharmeux, G Dubois, C Beauloye, S Wattiaux-De Coninck, R Waffiaux: Effect of various flavonoids on lysosomes subjected to an oxidative stress. Biochem Pharmacol 44, 1243-1248 (1992)
[8]AJ Day, G Williamson: Human metabolism of dietary quercetin glycosides, in: Gross, G.G., Hemingway, R.W., Yoshida T. (Eds.), Plant Polyphenols 2: Chemistry, Biology, Pharmacology, Ecology. Basic Life Sciences, vol. 66, Kluwer Academic/Plenum Publishers, New York, pp. 415–434 (1999)
[9]JM Harnly, RF Doherty, GR Beecher, JM Holden, DB Haytowitz, S Bhagwat, S Gebhardt: Flavonoid content of U.S. fruits, vegetables, and nuts. J Agric Food Chem 54, 9966-9977 (2006).
[10]EJr Middleton, C Kandaswami, TC Theoharides: The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease and cancer. Pharmacol Rev 42, 673-751 (2000).
[11]I Erlund: Review of the flavonoids quercetin, hesperetin and naringenin. Dietary sources, bioactivities and epidemiology. Nutr Res 24, 851-874 (2004).
[12]JH Carver, AV Carrano, JT MacGregor: Genetic effects of the flavonoids quercetin, Kaempferol and galangin on Chinese hamster ovary cells in vitro. Mutation Research 133, 45–60 (1983).
[13]JT MacGregor: Mutagenic and carcinogenic effects of flavonoids. In: Cody, VE Middlenton, JB Harbone, (Eds.), Plant Flavonoids in Biology and Medicine. Biochemical Pharmacological and Structure–Activity Relationships. Alan R Liss, New York, pp. 411–424 (1986).
[14]SC Sahu, GC Gray: Pro-oxidant activity of flavonoids: effects on glutathione and glutathione S-transferase in isolated rat liver nuclei. Cancer Letters 104, 193-196 (1996).
[15]W Peres, MJ Tunon, PS Collado, SM Herrmann, N Marroni, J Gonza lez-gallego: The flavonoids quercetin ameliorates liver damage in rats with biliary obstruction. Journal of Hepatology 33, 742–750 (2000).
[16]GL Benoni, D Cuzzolin, M Zambreri, Donini, P Del Soldato, I Caramazza: Gastrointestinal effects of single and repeated doses of ferrous sulphate in rats. Pharmacol Res 27, 73-80 (1993).
[17]N Leelayuwat, S Laddawan, Y Kanpetta, M Benja, D Wongpan, O Tunkamnerdthai, J Wattanathorn, S Muchimapura, J Yamauchi: Quercetin Enhances Endurance Capacity via Antioxidant Activity and Size of Muscle Fibre Type 1. Journal of Pharmacy and Nutrition Sciences 2, 160-164 (2012).
[18]J da Silva, SM Herrmann, V Heuser, W Peres, PN Marroni, J González-Gallego, B Erdtmann: Evaluation of the genotoxic effect of rutin and quercetin by comet assay and micronucleus test. Food Chem Toxicol 40(7), 941-7 (2002).
[19]RJ Preston, BJ Dean, S Galloway, H Holden, AF McFee, M Shelby: Mammalian in vivo cytogenetic assays. Analysis of chromosome aberrations in bone marrow cells. Mutat Res 189, 157-65 (1987).
[20]W Schmid: The micronucleus test. Mutat Res 31, 9-15 (1975).
[21]A Buschini, C Alessandrini, A Martino, L Pasini, V Rizzoli, C Carlo-Stella, P Poli, C Rossi: Bleomycin genotoxicity and amifostine (WR-2721) cell protection in normal leukocytes vs. K562 tumoral cells. Biochem Pharmacol 63, 967-75 (2002).
[22]RR Sokal, FJ Rohlf: Biometry. The principles and practice of statistics in biological research. 2nd (Eds.), WH Freeman Company, New York, pp. 859 (1981).
[23]KR Robbins, HW Norton, DH Baker: Estimation of nutrient requirements from growth data. J Nutr 109, 1710-1714 (1979).
[24]N Parveen, G.G.H.A. Shadab: Amelioration of Iron Induced Clastogenicity and DNA Damage in Wistar Rats by Thymoquinone. Science of Advanced Materials 6, 933-945 (2014).
[25]N Parveen, S Ahmad, G.G.H.A. Shadab: Iron induced genotoxicity: attenuation by vitamin C and its optimization. Interdisciplinary Toxicology 7(3), 154-158 (2014)
[26]N Parveen, G.G.H.A. Shadab: Iron Induced Oxidative Stress and Aging. Advanced Science, Engineering and Medicine 4, 181–189 (2012).
[27]N Parveen, G.G.H.A. Shadab: Ameliorative Action of Nigella Sativa Against Iron Induced Chromosomal Aberrations In Rat Bone Marrow Cells in vivo. International Journal of Pharma and Bio Sciences 2(2), 470-477 (2011).
[28]G.G.H.A. Shadab, N Parveen: Clastogenic Effects of Ferrous Sulfate on Human Lymphocyte Chromosomes in vitro. Advanced Science Letters 4, 3566-3569 (2011).
[29]S Okada: Iron in carcinogenesis in laboratory animals and humans: A mechanistic consideration and a review of literature. Int J Clin Oncol 3, 191-203 (1998)
[30]Y Hanasaki, S Ogawa, S Fukui: The correlation between active oxygens scavenging and antioxidative effects of flavonoids. Free Radic Biol Med 16, 845-850 (1994).
[31]F Ursini, M Maiorino, P Morazzoni, A Roveri, G Pifferi: A novel antioxidant flavonoid (IdB 1031) affecting molecular mechanisms of cellular activation. Free Radic Biol Med 16, 547-553 (1994).
[32]GR Buettner: The pecking order of free radicals and antioxidants: lipid peroxidation, alpha-tocopherol, and ascorbate. Arch Biochem Biophys 300, 535-543 (1993).
[33]PG Pietta: Flavonoids as antioxidants. J Nat Prod 63, 1035-1042 (2000).
[34]F Shahidi, PK Wanasundara: Phenolic antioxidants. Crit Rev Food Sci Nutr 32, 67-103 (1992).
[35]D Metodiewa, AK Jaiswal, N Cenas, E Dickancaite, J Segura-Aguilar: Quercetin may act as a cytotoxic prooxidant after its metabolic activation to semi quinone and quinoidal product. Free Radic Biol Med 26, 107–116 (1999).
[36]I Morel, G Lescoat, P Cogrel, O Sergent, N Pasdeloup, P Brissot, P Cillard, J Cillard: Antioxidant and iron-chelating activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures. Biochem Pharmacol 45, 13–19 (1993)
[37]CA Rice-Evans, NJ Miller, G Paganga: Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 20, 933-956 (1996).
[38]G Scambia, FO Ranelletti, BP Panici, M Piantelli, G Bonanno, R De Vincenzo, G Ferrandina, L Pierelli, A Capelli, S Mancuso: Quercetin inhibits the growth of a multidrug-resistant estrogen- receptor-negative MCF-7 human breast-cancer cell line expressing type II estrogen-binding sites. Cancer Chemother Pharmacol 28, 255-258 (1991).
[39]TM Elattar, AS Virji: The inhibitory effect of curcumin, genistein, quercetin and cisplatin on the growth of oral cancer cells in vitro, Anticancer Res 20, 1733-1738 (2000).
[40]S Caltagirone, C Rossi, A Poggi, FO Ranelletti, PG Natali, M Brunetti, FB Aiello, M Piantelli: Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential. Int J Cancer 87, 595-600 (2000).
[41]N Aligiannis, S Mitaku, D Mitrocotsa, S Leclerc: Flavonoids as cycline- dependent kinase inhibitors: inhibition of cdc 25 phosphatase activity by flavonoids belonging to the quercetin and kaempferol series. Planta Med 67, 468-470 (2001).
[42]SC Sahu, MC Washington: Quercetin-induced lipid peroxidation and DNA damage in isolated rat-liver nuclei. Cancer Lett 58, 75-79 (1991).
[43]M Yoshino, M Haneda, M Naruse, K Murakami: Prooxidant activity of flavonoids: copper-dependent strand breaks and the formation of 8-hydroxy-2-deoxyguanosine in DNA. Mol Genet Metab 68, 468-472 (1999).
[44]MJ Laughton, B Halliwell, PJ Evans, JR Hoult: Antioxidant and pro-oxidant actions of the plant phenolics quercetin, gossypol and myricetin. Effects on lipid peroxidation, hydroxyl radical generation and bleomycin-dependent damage to DNA. Biochem Pharmacol 38, 2859-2865 (1989).
[45]N Sugihara, T Arakawa, M Ohnishi, K Furuno: Anti- and prooxidative effects of flavonoids on metal-induced lipid hydroperoxidedependent lipid peroxidation in cultured hepatocytes loaded with alpha-linolenic acid. Free Radic Biol Med 27, 1313-1323 (1999).
[46]NM O’Brien, JA Woods, SA Aherne, YC O’Callaghan: Cytotoxicity, genotoxicity and oxidative reactions in cell-culture models: modulatory effects of phytochemicals. Biochem Soc Trans 28, 22-26 (2000).
[47]K Horvathova, L Novotny, D Tothova, A Vachalkova: Determination of free radical scavenging activity of quercetin, rutin, luteolin and apigenin in H2O2- treated human ML cells K562. Neoplasma 51, 395-399 (2004).
[48]K Horvathova, L Novotny, A Vachalkova: The free radical scavenging activity of four flavonoids determined by the comet assay. Neoplasma 50, 291-295 (2003).
[49]U Undeger, S Aydin, AA Basaran, N Basaran: The modulating effects of quercetin and rutin on the mitomycin C induced DNA damage. Toxicol Lett 151, 143-149 (2004).
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Frontiers in Bioscience-Scholar (FBS) is published by IMR Press from Volume 13 Issue 1 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
The dual clastogenic and anti-clastogenic properties of quercetin is dose dependent
1 Cytogenetics and Molecular Toxicology Lab, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, UP, India
*Author to whom correspondence should be addressed.
Abstract
Iron is a ubiquitous constituent of cytochromes, oxygen-binding molecules and a variety of enzymes because of its property to transition from ferric (Fe3+) to ferrous (Fe2+) state, leading to change in the redox potential. However, the same property accounts for free radical injury. In order to overcome harmful effects of iron we investigated the possible protective effect of quercetin (QCT), a flavonoid with antioxidant property, against the oxidative DNA damage caused by iron sulfate in vivo. We show that QCT exerts efficient anticlastogenic action in the context of iron sulfate treatment up to a dose of 500 mg/kg while it induces DNA damage at higher doses. These findings show that QCT has a dual effect; at low doses it ameliorates the oxidative damage produced by iron, and it is genotoxic and cytotoxic at a higher dose.
Keywords
- Iron
- Quercetin
- Chromosomal Aberration
- Micronucleus Test
- Comet Assay
- DNA Damage
References
- [1] ED Weinberg: The hazards of iron loading. Metallomics 2(11), 732-40 (2010).
- [2] B Halliwell, JMC Gutteridge: Role of free radicals and catalytic metal ions in human diseases: An overview. Methods Enzymol 186, 1-86 (1990)
- [3] HC Greenspan, OI Aruoma: Oxidative stress and apoptosis in HIV infection: a role for plant-derived metabolites with synergistic antioxidant activity. Immunol Today 15, 209-213 (1994)
- [4] W Bors, W Heller, C Michel Saran: Flavonoids as antioxidants: determination of radical-scavenging efficiencies. Methods Enzymol. 186, 343-355 (1990)
- [5] ME Inal, A Kahraman: The protective effect of flavonol quercetin against ultraviolet a induced oxidative stress in rats. Toxicology 154, 21-29 (2000)
- [6] MJ Laughton, PJ Evans, MA Moroney, JR Hoult, B Halliwell:Biochem Pharmacol 48, 1673-1680 (1991)
- [7] T Decharmeux, G Dubois, C Beauloye, S Wattiaux-De Coninck, R Waffiaux: Effect of various flavonoids on lysosomes subjected to an oxidative stress. Biochem Pharmacol 44, 1243-1248 (1992)
- [8] AJ Day, G Williamson: Human metabolism of dietary quercetin glycosides, in: Gross, G.G., Hemingway, R.W., Yoshida T. (Eds.), Plant Polyphenols 2: Chemistry, Biology, Pharmacology, Ecology. Basic Life Sciences, vol. 66, Kluwer Academic/Plenum Publishers, New York, pp. 415–434 (1999)
- [9] JM Harnly, RF Doherty, GR Beecher, JM Holden, DB Haytowitz, S Bhagwat, S Gebhardt: Flavonoid content of U.S. fruits, vegetables, and nuts. J Agric Food Chem 54, 9966-9977 (2006).
- [10] EJr Middleton, C Kandaswami, TC Theoharides: The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease and cancer. Pharmacol Rev 42, 673-751 (2000).
- [11] I Erlund: Review of the flavonoids quercetin, hesperetin and naringenin. Dietary sources, bioactivities and epidemiology. Nutr Res 24, 851-874 (2004).
- [12] JH Carver, AV Carrano, JT MacGregor: Genetic effects of the flavonoids quercetin, Kaempferol and galangin on Chinese hamster ovary cells in vitro. Mutation Research 133, 45–60 (1983).
- [13] JT MacGregor: Mutagenic and carcinogenic effects of flavonoids. In: Cody, VE Middlenton, JB Harbone, (Eds.), Plant Flavonoids in Biology and Medicine. Biochemical Pharmacological and Structure–Activity Relationships. Alan R Liss, New York, pp. 411–424 (1986).
- [14] SC Sahu, GC Gray: Pro-oxidant activity of flavonoids: effects on glutathione and glutathione S-transferase in isolated rat liver nuclei. Cancer Letters 104, 193-196 (1996).
- [15] W Peres, MJ Tunon, PS Collado, SM Herrmann, N Marroni, J Gonza lez-gallego: The flavonoids quercetin ameliorates liver damage in rats with biliary obstruction. Journal of Hepatology 33, 742–750 (2000).
- [16] GL Benoni, D Cuzzolin, M Zambreri, Donini, P Del Soldato, I Caramazza: Gastrointestinal effects of single and repeated doses of ferrous sulphate in rats. Pharmacol Res 27, 73-80 (1993).
- [17] N Leelayuwat, S Laddawan, Y Kanpetta, M Benja, D Wongpan, O Tunkamnerdthai, J Wattanathorn, S Muchimapura, J Yamauchi: Quercetin Enhances Endurance Capacity via Antioxidant Activity and Size of Muscle Fibre Type 1. Journal of Pharmacy and Nutrition Sciences 2, 160-164 (2012).
- [18] J da Silva, SM Herrmann, V Heuser, W Peres, PN Marroni, J González-Gallego, B Erdtmann: Evaluation of the genotoxic effect of rutin and quercetin by comet assay and micronucleus test. Food Chem Toxicol 40(7), 941-7 (2002).
- [19] RJ Preston, BJ Dean, S Galloway, H Holden, AF McFee, M Shelby: Mammalian in vivo cytogenetic assays. Analysis of chromosome aberrations in bone marrow cells. Mutat Res 189, 157-65 (1987).
- [20] W Schmid: The micronucleus test. Mutat Res 31, 9-15 (1975).
- [21] A Buschini, C Alessandrini, A Martino, L Pasini, V Rizzoli, C Carlo-Stella, P Poli, C Rossi: Bleomycin genotoxicity and amifostine (WR-2721) cell protection in normal leukocytes vs. K562 tumoral cells. Biochem Pharmacol 63, 967-75 (2002).
- [22] RR Sokal, FJ Rohlf: Biometry. The principles and practice of statistics in biological research. 2nd (Eds.), WH Freeman Company, New York, pp. 859 (1981).
- [23] KR Robbins, HW Norton, DH Baker: Estimation of nutrient requirements from growth data. J Nutr 109, 1710-1714 (1979).
- [24] N Parveen, G.G.H.A. Shadab: Amelioration of Iron Induced Clastogenicity and DNA Damage in Wistar Rats by Thymoquinone. Science of Advanced Materials 6, 933-945 (2014).
- [25] N Parveen, S Ahmad, G.G.H.A. Shadab: Iron induced genotoxicity: attenuation by vitamin C and its optimization. Interdisciplinary Toxicology 7(3), 154-158 (2014)
- [26] N Parveen, G.G.H.A. Shadab: Iron Induced Oxidative Stress and Aging. Advanced Science, Engineering and Medicine 4, 181–189 (2012).
- [27] N Parveen, G.G.H.A. Shadab: Ameliorative Action of Nigella Sativa Against Iron Induced Chromosomal Aberrations In Rat Bone Marrow Cells in vivo. International Journal of Pharma and Bio Sciences 2(2), 470-477 (2011).
- [28] G.G.H.A. Shadab, N Parveen: Clastogenic Effects of Ferrous Sulfate on Human Lymphocyte Chromosomes in vitro. Advanced Science Letters 4, 3566-3569 (2011).
- [29] S Okada: Iron in carcinogenesis in laboratory animals and humans: A mechanistic consideration and a review of literature. Int J Clin Oncol 3, 191-203 (1998)
- [30] Y Hanasaki, S Ogawa, S Fukui: The correlation between active oxygens scavenging and antioxidative effects of flavonoids. Free Radic Biol Med 16, 845-850 (1994).
- [31] F Ursini, M Maiorino, P Morazzoni, A Roveri, G Pifferi: A novel antioxidant flavonoid (IdB 1031) affecting molecular mechanisms of cellular activation. Free Radic Biol Med 16, 547-553 (1994).
- [32] GR Buettner: The pecking order of free radicals and antioxidants: lipid peroxidation, alpha-tocopherol, and ascorbate. Arch Biochem Biophys 300, 535-543 (1993).
- [33] PG Pietta: Flavonoids as antioxidants. J Nat Prod 63, 1035-1042 (2000).
- [34] F Shahidi, PK Wanasundara: Phenolic antioxidants. Crit Rev Food Sci Nutr 32, 67-103 (1992).
- [35] D Metodiewa, AK Jaiswal, N Cenas, E Dickancaite, J Segura-Aguilar: Quercetin may act as a cytotoxic prooxidant after its metabolic activation to semi quinone and quinoidal product. Free Radic Biol Med 26, 107–116 (1999).
- [36] I Morel, G Lescoat, P Cogrel, O Sergent, N Pasdeloup, P Brissot, P Cillard, J Cillard: Antioxidant and iron-chelating activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures. Biochem Pharmacol 45, 13–19 (1993)
- [37] CA Rice-Evans, NJ Miller, G Paganga: Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 20, 933-956 (1996).
- [38] G Scambia, FO Ranelletti, BP Panici, M Piantelli, G Bonanno, R De Vincenzo, G Ferrandina, L Pierelli, A Capelli, S Mancuso: Quercetin inhibits the growth of a multidrug-resistant estrogen- receptor-negative MCF-7 human breast-cancer cell line expressing type II estrogen-binding sites. Cancer Chemother Pharmacol 28, 255-258 (1991).
- [39] TM Elattar, AS Virji: The inhibitory effect of curcumin, genistein, quercetin and cisplatin on the growth of oral cancer cells in vitro, Anticancer Res 20, 1733-1738 (2000).
- [40] S Caltagirone, C Rossi, A Poggi, FO Ranelletti, PG Natali, M Brunetti, FB Aiello, M Piantelli: Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential. Int J Cancer 87, 595-600 (2000).
- [41] N Aligiannis, S Mitaku, D Mitrocotsa, S Leclerc: Flavonoids as cycline- dependent kinase inhibitors: inhibition of cdc 25 phosphatase activity by flavonoids belonging to the quercetin and kaempferol series. Planta Med 67, 468-470 (2001).
- [42] SC Sahu, MC Washington: Quercetin-induced lipid peroxidation and DNA damage in isolated rat-liver nuclei. Cancer Lett 58, 75-79 (1991).
- [43] M Yoshino, M Haneda, M Naruse, K Murakami: Prooxidant activity of flavonoids: copper-dependent strand breaks and the formation of 8-hydroxy-2-deoxyguanosine in DNA. Mol Genet Metab 68, 468-472 (1999).
- [44] MJ Laughton, B Halliwell, PJ Evans, JR Hoult: Antioxidant and pro-oxidant actions of the plant phenolics quercetin, gossypol and myricetin. Effects on lipid peroxidation, hydroxyl radical generation and bleomycin-dependent damage to DNA. Biochem Pharmacol 38, 2859-2865 (1989).
- [45] N Sugihara, T Arakawa, M Ohnishi, K Furuno: Anti- and prooxidative effects of flavonoids on metal-induced lipid hydroperoxidedependent lipid peroxidation in cultured hepatocytes loaded with alpha-linolenic acid. Free Radic Biol Med 27, 1313-1323 (1999).
- [46] NM O’Brien, JA Woods, SA Aherne, YC O’Callaghan: Cytotoxicity, genotoxicity and oxidative reactions in cell-culture models: modulatory effects of phytochemicals. Biochem Soc Trans 28, 22-26 (2000).
- [47] K Horvathova, L Novotny, D Tothova, A Vachalkova: Determination of free radical scavenging activity of quercetin, rutin, luteolin and apigenin in H2O2- treated human ML cells K562. Neoplasma 51, 395-399 (2004).
- [48] K Horvathova, L Novotny, A Vachalkova: The free radical scavenging activity of four flavonoids determined by the comet assay. Neoplasma 50, 291-295 (2003).
- [49] U Undeger, S Aydin, AA Basaran, N Basaran: The modulating effects of quercetin and rutin on the mitomycin C induced DNA damage. Toxicol Lett 151, 143-149 (2004).
