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Recovery of adriamycin induced mitochondrial dysfunction in liver by selenium

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Abstract

Adriamycin (ADR) is a chemotherapeutic drug. Its toxicities may associate with mitochondriopathy. Selenium (Se) is a trace element for essential intracellular antioxidant enzymes. However, there is lack of data related to the effect of selenium on the liver tissue of ADR-induced mitochondrial dysfunction. The study was to investigate whether Se could restore mitochondrial dysfunction of liver-exposed ADR. Rats were divided into four groups as a control, ADR, Se, co-treated ADR with Se groups. The biochemical measurements of the liver were made in mitochondrial and cytosol. ATP level and mitochondria membrane potential (MMP) were measured. Total oxidant (TOS), total antioxidant (TAS) status were determined and oxidative stress index (OSI) was calculated by using TOS and TAS. ADR increased TOS in mitochondria and also oxidative stress in mitochondria. ADR sligtly decreased MMP, and ATP level. Partial recovery of MMP by Se was able to elevate the ATP production in cotreatment of ADR with Se. TOS in mitochondria and cytosol was diminished, as well as OSI. We concluded that selenium could potentially be used against oxidative stress induced by ADR in liver, resulting from the restoration of MMP and ATP production and prevention of mitochondrial damage in vivo.

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References

  • Alshabanah OA, Hafez MM, Al-Harbi MM, Hassan ZK, Al Rejaie SS, Asiri YA, Sayed-Ahmed MM (2010) Doxorubicin toxicity can be ameliorated during antioxidant L-carnitine supplementation. Oxid Med Cell Longev 3:428–433. doi:10.4161/oxim.3.6.14416

  • Ascensão A, Magalhães J, Soares JM, Ferreira R, Neuparth MJ, Marques F, Oliveira PJ, Duarte JA (2005) Moderate endurance training prevents doxorubicin induced in vivo mitochondriopathy and reduces the development of cardiac apoptosis. Am J Physiol Heart Circ Physiol 289:H722–731. doi:10.1152/ajpheart.01249.2004

  • Barogi S, Baracca A, Cavazzoni M, Parenti Castelli G, Lenaz G (2000) Effect of the oxidative stress induced by adriamycin on rat hepatocyte bioenergetics during ageing. Mech ageing Dev 113:1–21. doi:10.1016/S0047-6374(99)00089-55

  • Benchekroun MN, Pourquier P, Schott B, Robert J (1993) Doxorubicin-induced lipid peroxidation and glutathione peroxidase activity in tumor cell lines selected for resistance to doxorubicin. Eur J Biochem 211:141–146

    Article  CAS  Google Scholar 

  • Benedetti S, Primiterra M, Tagliamonte MC, Carnevali A, Gianotti A, Bordoni A, Canestrari F (2012) Counteraction of oxidative damage in the rat liver by an ancient grain (Kamut brand khorasan wheat). Nutrition 28:436–441. doi:10.1016/j.nut.2011.08.006

    Article  CAS  Google Scholar 

  • Bordoni A, Danesi F, Malaguti M, Di Nunzio M, Pasqui F, Maranesi M, Biagi PL (2008) Dietary selenium for the counteraction of oxidative damage: fortified foods or supplements? Br J Nutr 99:191–197. doi:10.1017/S0007114507793911

    Article  CAS  Google Scholar 

  • Bulucu F, Ocal R, Karadurmus N, Sahin M, Kenar L, Aydin A, Oktenli C, Koc B, Inal V, Yamanel L, Yaman H (2009) Effects of N-acetylcysteine, deferoxamine and selenium on doxorubicin-induced hepatotoxicity. Biol Trace Elem Res 132:184–196. doi:10.1007/s12011-009-8377-y

  • Chautan M, Leonardi J, Calaf R, Lechene P, Grataroli R, Portugal H, Pauli AM, Lafont H, Nalbone G (1992) Heart and liver membrane phospholipid homeostasis during acute administration of various antitumoral drugs to the rat. Biochem Pharmacol 44:1139–1147. doi:10.1016/0006-2952(92)90378-V

  • Chen XS, Xue A, Morris VC, Ferrans VJ, Herman EH, el-Hage A, Levander OA (1986) Effect of selenium deficiency on the chronic toxicity of adriamycin in rats. J Nutr 116:2453–2465

    CAS  Google Scholar 

  • Chen JY, Hu RY, Chou HC (2013) Quercetin-induced cardioprotection against doxorubicin cytotoxicity. J Biomed Sci 20:95. doi:10.1186/1423-0127-20-95

    Article  Google Scholar 

  • Cheng X, Gao F, Xiang J, Jiang X, Chen J, Zhang J (2011) Galactosylated alpha, beta-poly[(2-hydroxyethyl)-L-aspartamide]-bound doxorubicin: improved antitumor activity against hepatocellular carcinoma with reduced hepatotoxicity. Anticancer Drug 22:136–147. doi:10.1097/CAD.0b013e3283406e85

  • Dudka J, Gieroba R, Korga A, Burdan F, Matysiak W, Jodlowska-Jedrych B, Mandziuk S, Korobowicz E, Murias M (2012) Different effects of resveratrol on dose-related doxorubicin-induced heart and liver toxicity. Evid Based Complement Alternat Med 2012:606183. doi:10.1155/2012/606183

  • Dursun N, Taskin E, Yerer Aycan MB, Sahin L (2011) Selenium-mediated cardioprotection against adriamycin-induced mitochondrial damage. Drug Chem Toxicol 34:199–207. doi:10.3109/01480545.2010.538693

    Article  CAS  Google Scholar 

  • Fischer JG, Tackett RL, Howerth EW, Johnson MA (1992) Copper and selenium deficiencies do not enhance the cardiotoxicity in rats due to chronic doxorubicin treatment. J Nutr 122:2128–2137

    CAS  Google Scholar 

  • Goldstein I, Rivlin N, Shoshana OY, Ezra O, Madar S, Goldfinger N, Rotter V (2013) Chemotherapeutic agents induce the expression and activity of their clearing enzyme CYP3A4 by activating p53. Carcinogenesis 34:190–198. doi:10.1093/carcin/bgs318

    Article  CAS  Google Scholar 

  • Hanusova V, Tomsik P, Kriesfalusyova L, Pakostova A, Bousova I, Skalova L (2013) In vivo effect of oracin on doxorubicin reduction, biodistribution and efficacy in Ehrlich tumor bearing mice. Pharmacol Rep 65:445–452

    Article  CAS  Google Scholar 

  • Hida H, Coudray C, Calop J, Favier A (1995) Effect of antioxidants on adriamycin-induced microsomal lipid peroxidation. Biol Trace Elem Res 47:111–116. doi:10.1007/BF02790107

    Article  CAS  Google Scholar 

  • Ingawale DK, Mandlik SK, Naik SR (2014) Models of hepatotoxicity and the underlying cellular, biochemical and immunological mechanism(s): a critical discussion. Environ Toxicol Pharmacol 37:118–133. doi:10.1016/j.etap.2013.08.015

    Article  CAS  Google Scholar 

  • Koukay N, Mouhieddine S, Richard MJ, Arnaud J, de Leiris J, Favier A (1990) Influence of selenium on lipid peroxidation and cardiac functions in chronically adriamycin-treated rats. Adv Exp Med Biol 264:353–359

    Article  CAS  Google Scholar 

  • Manjanatha MG, Bishop ME, Pearce MG, Kulkarni R, Lyn-Cook LE, Ding W (2014) Genotoxicity of doxorubicin in F344 rats by combining the comet assay, flow-cytometric peripheral blood micronucleus test, and pathway-focused gene expression profiling. Environ Mol Mutagen 55:24–34. doi:10.1002/em.21822

    Article  CAS  Google Scholar 

  • Myers CE, Katki A, Travis E (1982) Effect of tocopherol and selenium on defenses against reactive oxygen species and their effect on radiation sensitivity. Ann NY Acad Sci 393:419–425

    Article  CAS  Google Scholar 

  • Octavia Y, Tocchetti CG, Gabrielson KL, Janssens S, Crijns HJ, Moens AL (2012) Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeutic strategies. J Mol Cell Cardiol 52:1213–1225. doi:10.1016/j.yjmcc.2012.03.006

    Article  CAS  Google Scholar 

  • Ozdogan K, Taskin E, Dursun N (2011) Protective effect of carnosine on adriamycin-induced oxidative heart damage in rats. Anadolu Kardiyol Derg 11:3–10. doi:10.5152/akd.2011.003

    Article  Google Scholar 

  • Pereira GC, Pereira SP, Pereira CV, Lumini JA, Magalhães J, Ascensão A, Santos MS, Moreno AJ, Oliveira PJ (2012) Mitochondrionopathy phenotype in doxorubicin-treated Wistar rats depends on treatment protocol and is cardiac-specific. PLoS One 7(6):e38867. doi:10.1371/journal.pone.0038867

  • Popovic M, Kolarovic J, Mikov M, Trivic S, Kaurinovic B (2007) Anthracycline-based combined chemotherapy in the mouse model. Eur J Drug Metab Pharmacokinet 32:101–108

    Article  CAS  Google Scholar 

  • Prahalathan C, Selvakumar E, Varalakshmi P (2005) Lipoic acid ameliorates adriamycin-induced testicular mitochondriopathy. Reprod Toxicol 20:111–116. doi:10.1016/j.reprotox.2004.12.005

    Article  CAS  Google Scholar 

  • Qian H, Yang Y, Wang X (2011) Curcumin enhanced adriamycin-induced human liver-derived Hepatoma G2 cell death through activation of mitochondria-mediated apoptosis and autophagy. Eur J Pharm Sci 43:125–131. doi:10.1016/j.ejps.2011.04.002

    Article  CAS  Google Scholar 

  • Raskovic A, Stilinovic N, Kolarovic J, Vasovic V, Vukmirovic S, Mikov M (2011) The protective effects of silymarin against doxorubicin-induced cardiotoxicity and hepatotoxicity in rats. Molecules 16:8601–8613. doi:10.3390/molecules16108601

    Article  CAS  Google Scholar 

  • Revis NW, Marusic N (1978) Glutathione peroxidase activity and selenium concentration in the hearts of doxorubicin-treated rabbits. J Mol Cell Cardiol 10:945–951. doi:10.1016/0022-2828(78)90340-1

  • Sokolove PM (1994) Interactions of adriamycin aglycones with mitochondria may mediate adriamycin cardiotoxicity. Int J Biochem 26:1341–1350

    Article  CAS  Google Scholar 

  • Tacar O, Sriamornsak P, Dass CR (2013) Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol 65:157–170. doi:10.1111/j.2042-7158.2012.01567.x

    Article  CAS  Google Scholar 

  • Tan L, Jia X, Jiang X, Zhang Y, Tang H, Yao S, Xie Q (2009) In vitro study on the individual and synergistic cytotoxicity of adriamycin and selenium nanoparticles against Bel7402 cells with a quartz crystal microbalance. Biosens Bioelectron 24:2268–2272. doi:10.1016/j.bios.2008.10.030

    Article  CAS  Google Scholar 

  • Taskin E, Dursun N (2012) The protection of selenium on adriamycin-induced mitochondrial damage in rat. Biol Trace Elem Res 147:165–171. doi:10.1007/s12011-011-9273-9

    Article  CAS  Google Scholar 

  • Taskin E, Ozdogan K, Kunduz KE, Dursun N (2014) The restoration of kidney mitochondria function by inhibition of angiotensin-II production in rats with acute adriamycin-induced nephrotoxicity. Ren Fail 36(4):606–612. doi:10.3109/0886022X.2014.882737

  • Vadgama JV, Wu Y, Shen D, Hsia S, Block J (2000) Effect of selenium in combination with adriamycin or taxol on several different cancer cells. Anticancer Res 20:1391–1414

    CAS  Google Scholar 

  • Wang GW, Kang YJ (1999) Inhibition of doxorubicin toxicity in cultured neonatal mouse cardiomyocytes with elevated metallothionein levels. J Pharmacol Exp Ther 288:938–944

    CAS  Google Scholar 

  • Wang B, Van Veldhoven PP, Brees C, Rubio N, Nordgren M, Apanasets O, Kunze M, Baes M, Agostinis P, Fransen M (2013) Mitochondria are targets for peroxisome-derived oxidative stress in cultured mammalian cells. Free Radic Biol Med 65:882–894. doi:10.1016/j.freeradbiomed.2013.08.173

  • Wang B, Ma Y, Kong X, Ding X, Gu H, Chu T, Ying W (2014) NAD administration decreases doxorubicin-induced liver damage of mice by enhancing antioxidation capacity and decreasing DNA damage. Chem Biol Interact. 212:65–71. doi:10.1016/j.cbi.2014.01.013

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Acknowledgments

The authors wish to tank to Assoc. Prof. Dr. Mukerrem Betul YERER AYCAN for helping to use a fluorescent plate reader, to Prof. Dr. Cem SUER and Prof. Dr. Yunus DURSUN to help analysis the data. This study was supported financially by the Research Foundation of Erciyes University.

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The authors have no conflicts of interest to disclose.

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Taskin, E., Dursun, N. Recovery of adriamycin induced mitochondrial dysfunction in liver by selenium. Cytotechnology 67, 977–986 (2015). https://doi.org/10.1007/s10616-014-9736-x

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