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2014 | 61 | 1 | 7-11
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The effect of quercetin on oxidative DNA damage and myelosuppression induced by etoposide in bone marrow cells of rats

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There is increasing evidence for the existence of an association between the presence of etoposide phenoxyl radicals and the development of treatment-related acute myeloid leukemia (t-AML), which occurs in a few percent of patients treated with this chemotherapeutic agent. The most common side effect caused by etoposide is myelosuppression, which limits the use of this effective drug. The goal of the study was to investigate the influence of antioxidant querectin on myelosuppression and oxidative DNA damage caused by etoposide. The influence of quercetin and/or etoposide on oxidative DNA damage was investigated in LT-12 cell line and bone marrow cells of rats via comet assay. The effect of quercetin on myelosuppression induced by etoposide was invetsigated by cytological analysis of bone marrow smears stained with May-Grünwald-Giemsa stain. Etoposide caused a significant increase in oxidative DNA damage in bone marrow cells and LT-12 cell line in comparison to the appropriate controls. Quercetin significantly reduced the oxidative DNA damage caused by etoposide both in vitro and in vivo. Quercetin also significantly protected against a decrease in the percentage of myeloid precursors and erythroid nucleated cells caused by etoposide administration in comparison to the group treated with etoposide alone. The results of the study indicate that quercetin could be considered a protectively acting compound in bone marrow cells during etoposide therapy.
Physical description
  • Department of Cytobiology, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland
  • Awad HM, Boersma MG, Boeren S, van der Woude H, van Zanden J, van Bladeren PJ, Vervoort J, Rietjens IM (2002) Identification of o-quinone/quinone methide metabolites of quercetin in a cellular in vitro system. FEBS Lett 520: 30-34.
  • Bakheet SA (2011) Assessment of Anti-Cytogenotoxic Effects of Quercetin in Animals Treated with Topotecan. Oxid Med Cell Longev 2011: 824597.
  • Battisti V, Maders LD, Bagatini MD, Santos KF, Spanevello RM, Maldonado PA, Brulé AO, Araújo Mdo C, Schetinger MR, Morsch VM (2008) Measurement of oxidative stress and antioxidant status in acute lymphoblastic leukemia patients. Clin Biochem 41: 511-528.
  • Boots AW, Li H, Schins RP, Duffin R, Heemskerk JW, Bast A, Haenen GR (2007) The quercetin paradox. Toxicol Appl Pharmacol 222: 89-96.
  • Brisdelli F, Coccia C, Cinque B, Cifone MG, Bozzi A (2007) Induction of apoptosis by quercetin: different response of human chronic myeloid (K562) and acute lymphoblastic (HSB-2) leukemia cells. Mol Cell Biochem 296: 137-149.
  • Choi EJ, Chee KM, Lee BH (2003) Anti- and prooxidant effects of chronic quercetin administration in rats. Eur J Pharmacol 482: 281-285.
  • Fabiani R, De Bartolomeo A, Rosignoli P, Morozzi G (2001) Antioxidants prevent the lymphocyte DNA damage induced by PMA-stimulated monocytes, Nutr Cancer 39: 284-291.
  • Feng R, Ni HM, Wang SY, Tourkova IL, Shurin MR, Harada H (2007) Cyanidin-3-rutinoside, a natural polyphenol antioxidant, selectively kills leukemia cells by induction of oxidative stress. J Biol Chem 282: 13468-13476.
  • Haim N, Nemec J, Roman J, Sinha B (1987) Peroxidase-catalyzed metabolism of etoposide (VP-16-213) and covalent binding of reactive intermediates to cellular macromolecules. Cancer Res 47: 5835-5840.
  • Hu JP, Calomme M, Lasure A, De Bruyne T, Pieters L, Vlietinck A, Vanden Berghe DA (1995) Structure-activity relationship of flavonoids with superoxide scavenging activity. Boil Trace Elem Res 47: 327-331.
  • Irie M, Miyata M, Kasai H (2005) Depression and possible cancer risk due to oxidative DNA damage. J Psychiatr Res 39: 553-60.
  • Ishiyama K, Satoh S, Igarashi Y, Kumagai H, Yahagi A, Sasaki H (1994) Flow cytometric analysis of the cell cycle of the leukemic cell lines treated with etoposide and cytosine arabinoside. Tohoku J Exp Med 174: 95-107.
  • Kagan VE, Yalowich JC, Borisenko GG, Tyurina YY, Tyurin VA, Thampatty P, Fabisiak JP (1999) Mechanism-based chemopreventive strategies against etoposide-induced acute myeloid leukemia: free radical/antioxidant approach. Mol Pharmacol 56: 494-506.
  • Kapiszewska M, Cierniak A, Papiez MA, Pietrzycka A, Stepniewski M, Lomnicki A (2007) Prolonged quercetin administration diminishes the etoposide-induced DNA damage in bone marrow cells of rats. Drug Chem Toxicol 30: 67-81.
  • Kasapović J, Pejić S, Stojiljković V, Todorović A, Radošević-Jelić L, Saičić ZS, Pajović SB (2010) Antioxidant status and lipid peroxidation in the blood of breast cancer patients of different ages after chemotherapy with 5-fluorouracil, doxorubicin and cyclophosphamide. Clin Biochem 43: 1287-1293.
  • Kobayashi K, Ratain MJ (1994) Pharmacodynamics and long-term toxicity of etoposide. Cancer Chemother Pharmacol 34: S64-S68.
  • Papież MA, Cierniak A, Krzyściak W, Bzowska M, Taha HM, Józkowicz A, Piskuła M. (2008) The changes of antioxidant defense system caused by quercetin administration do not lead to DNA damage and apoptosis in the spleen and bone marrow cells of rats. Food Chem Toxicol 46: 3053-3058.
  • Papież MA (2013) The influence of curcumin and (-)-epicatechin on the genotoxicity and myelosuppression induced by etoposide in bone marrow cells of male rats. Drug Chem Toxicol 36: 93-101.
  • Sallmyr A, Fan J, Rassool FV (2008) Genomic instability in myeloid malignancies: increased reactive oxygen species (ROS), DNA double strand breaks (DSBs), and error-prone repair. Cancer Lett 270: 1-9.
  • Sekeroglu ZA, Sekeroglu V (2012) Effects of Viscum album L. extract and quercetin on methotrexate-induced cyto-genotoxicity in mouse bone-marrow cells. Mutation Res 746: 56-59.
  • Shammas MA, Neri P, Koley H, Batchu RB, Bertheau RC, Munshi V, Prabhala R, Fulciniti MF, Tai YT, Treon SP, Goyal RK, Anderson KC, Munshi NC (2006) Specific killing of multiple myeloma cells by (−)-epigallocatechin-3-gallate extracted from green tea: biologic activity and therapeutic implications. Blood 108: 2804-2810.
  • Tice RR, Andrews PW, Hirai O, Singh NP (1991) The single cell gel (SCG) assay: an electrophoretic technique for the detection of DNA damage in individual cells. Adv Exp Med Biol 283: 157-164.
  • Turner SD, Wijnhoven SW, Tinwell H, Lashford LS, Rafferty JA, Ashby J, Vrieling H, Fairbairn LJ (2001) Assays to predict the genotoxicity of the chromosomal mutagen etoposide - focusing on the best assay. Mutation Res 493: 139-147.
  • Vlasova II, Feng WH, Goff JP, Giorgianni A, Do D, Gollin SM, Lewis DW, Kagan VE, Yalowich JC (2011) Myeloperoxidase-dependent oxidation of etoposide in human myeloid progenitor CD34+cells. Mol Pharmacol 79: 479-487.
  • Whitlock JA, Greer JP, Lukens JN (1991) Epipodophyllotoxin-related leukemia. Identification of a new subset of secondary leukemia. Cancer 68: 600-604.
  • Wilms LC, Hollman PC, Boots AW, Kleinjans JC (2005) Protection by quercetin and quercetin-rich fruit juice against induction of oxidative DNA damage and formation of BPDE-DNA adducts in human lymphocytes. Mutat Res 582: 155-162.
  • Zhou F, Zhang W, Wei Y, Zhou D, Su Z, Meng X, Hui L, Tian W (2007) The changes of oxidative stress and human 8-hydroxyguanine glycosylase 1 gene expression in depressive patients with acute leukemia. Leuk Res 31: 387-393.
  • Zhou FL, Zhang WG, Wei YC, Meng S, Bai GG, Wang BY, Yang HY, Tian W, Meng X, Zhang H, Chen SP (2010) Involvement of oxidative stress in the relapse of acute myeloid leukaemia. J Biol Chem 285: 15010-15015.
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