Biological Trace Element Research

, Volume 147, Issue 1–3, pp 165–171 | Cite as

The Protection of Selenium on Adriamycin-Induced Mitochondrial Damage in Rat

  • Eylem Taskin
  • Nurcan Dursun


Although adriamycin (ADR) exhibits high anti-tumor efficacy in vitro, its clinical use in cancer chemotherapy is limited due to its high renal toxicity. This study investigated the mechanism of ADR nephropathy and the protective effect of selenium on ADR-induced kidney damage by analyzing of the relationship between selenium and mitochondria. Rats were divided into four groups. The first group was injected with saline i.p. for 21 days, the second group received the 4 mg/kg i.p. ADR every alternate day for 8 days, the third group received the 50 μg/kg i.p. Se for 21 days, and the fourth group received the Se. ADR co-administration i.p. blood pressures were assessed, the mitochondrial membrane potential (MMP) was assessed, and the adenosine triphosphate (ATP) levels were determined. The total antioxidant (TAS) and oxidant status (TOS) in cytosol, the mitochondria of kidney cells, and plasma were measured. Mitochondrial TAS decreased and TOS increased in the ADR group compared to the Se group. ADR-treated rats showed significantly lower MMP than did the control and Se groups. MMP was significantly restored in the Se + ADR group through selenium treatment compared to the ADR group (p < 0.01). In the ADR group, a reduction in ATP content was seen compared to the control and Se groups (p < 0.01). ATP level was significantly restored through treatment with selenium in the Se + ADR group compared to the ADR group (p < 0.01). We concluded that selenium is effective in vivo against ADR-induced kidney damage via the restoration of TAS and TOS, which prevented mitochondrial damage.


Adriamycin Selenium Mitochondrial membrane potential ATP Total antioxidant status Total oxidant status 


  1. 1.
    Rossmann P, Matousovic K, Bohdanecka M (1993) Experimental adriamycin nephropathy. Fine structure, morphometry, glomerular polyanion, and cell membrane antigens. J Pathol 169:99–108PubMedCrossRefGoogle Scholar
  2. 2.
    Wang Y, Wang YP, Tay YC, Harris DC (2000) Progressive adriamycin nephropathy in mice: sequence of histologic and immunohistochemical events. Kidney Int 58:1797–1804PubMedCrossRefGoogle Scholar
  3. 3.
    Wharram BL, Goyal M, Wiggins JE et al (2005) Podocyte depletion causes glomerulosclerosis: diphtheria toxin-induced podocyte depletion in rats expressing human diphtheria toxin receptor transgene. J Am Soc Nephrol 16:2941–2952PubMedCrossRefGoogle Scholar
  4. 4.
    Wiggins JE, Goyal M, Sanden SK et al (2005) Podocyte hypertrophy, “adaptation,” and “decompensation” associated with glomerular enlargement and glomerulosclerosis in the aging rat: prevention by calorie restriction. J Am Soc Nephrol 16:2953–2966PubMedCrossRefGoogle Scholar
  5. 5.
    Bertani T, Poggi A, Pozzoni R et al (1982) Adriamycin-induced nephrotic syndrome in rats: sequence of pathologic events. Lab Invest 46:16–23PubMedGoogle Scholar
  6. 6.
    Cao Q, Wang Y, Zheng D et al (2010) IL-10/TGF-beta-modified macrophages induce regulatory T cells and protect against adriamycin nephrosis. J Am Soc Nephrol 21:933–942PubMedCrossRefGoogle Scholar
  7. 7.
    Paczek L, Teschner M, Schaefer RM et al (1992) Intraglomerular proteinase activity in adriamycin-induced nephropathy. Nephron 60:81–86PubMedCrossRefGoogle Scholar
  8. 8.
    Coers W, Huitema S, van der Horst ML, Weening JJ (1994) Puromycin aminonucleoside and adriamycin disturb cytoskeletal and extracellular matrix protein organization, but not protein synthesis of cultured glomerular epithelial cells. Exp Nephrol 2:40–50PubMedGoogle Scholar
  9. 9.
    Akman SA, Doroshow JH, Burke TG, Dizdaroglu M (1992) DNA base modifications induced in isolated human chromatin by NADH dehydrogenase-catalyzed reduction of doxorubicin. Biochemistry 31:3500–3506PubMedCrossRefGoogle Scholar
  10. 10.
    Adachi K, Fujiura Y, Mayumi F et al (1993) A deletion of mitochondrial DNA in murine doxorubicin-induced cardiotoxicity. Biochem Biophys Res Commun 195:945–951PubMedCrossRefGoogle Scholar
  11. 11.
    Lebrecht D, Kokkori A, Ketelsen UP, Setzer B, Walker UA (2005) Tissue-specific mtDNA lesions and radical-associated mitochondrial dysfunction in human hearts exposed to doxorubicin. J Pathol 207:436–444PubMedCrossRefGoogle Scholar
  12. 12.
    Suliman HB, Carraway MS, Ali AS et al (2007) The CO/HO system reverses inhibition of mitochondrial biogenesis and prevents murine doxorubicin cardiomyopathy. J Clin Invest 117:3730–3741PubMedGoogle Scholar
  13. 13.
    Santos DL, Moreno AJ, Leino RL, Froberg MK, Wallace KB (2002) Carvedilol protects against doxorubicin-induced mitochondrial cardiomyopathy. Toxicol Appl Pharmacol 185:218–227PubMedCrossRefGoogle Scholar
  14. 14.
    Michiels C, Raes M, Toussant O, Remacle J (1994) Importance of Se glutathione peroxidase, catalase and Cu/Zn-SOD for cell survival against oxidative stress. Free Radic Biol Med 17:235–248PubMedCrossRefGoogle Scholar
  15. 15.
    Rayman MP (2000) The importance of selenium to human health. Lancet 356:233–241PubMedCrossRefGoogle Scholar
  16. 16.
    Takahashi K, Newburger PE, Cohen HJ (1986) Glutathione peroxidase protein. Absence in selenium deficiency states and correlation with enzymatic activity. J Clin Invest 77:1402–1404PubMedCrossRefGoogle Scholar
  17. 17.
    Dursun N, Taskin E, Yerer Aycan MB, Sahin L (2011) Selenium-mediated cardioprotection against adriamycin-induced mitochondrial damage. Drug Chem Toxicol 34:199–207PubMedCrossRefGoogle Scholar
  18. 18.
    Xin YF, Zhou GL, Deng ZY et al (2007) Protective effect of Lycium barbarum on doxorubicin-induced cardiotoxicity. Phytother Res 21:1020–1024PubMedCrossRefGoogle Scholar
  19. 19.
    Hiraumi Y, Iwai-Kanai E, Baba S et al (2009) Granulocyte colony-stimulating factor protects cardiac mitochondria in the early phase of cardiac injury. Am J Physiol Heart Circ Physiol 296:H823–H832PubMedCrossRefGoogle Scholar
  20. 20.
    Gan L, Liu Q, Xu HB, Zhu YS, Yang XL (2002) Effects of selenium overexposure on glutathione peroxidase and thioredoxin reductase gene expressions and activities. Biol Trace Elem Res 89:165–175PubMedCrossRefGoogle Scholar
  21. 21.
    Martin M, Macias M, Leon J et al (2002) Melatonin increases the activity of the oxidative phosphorylation enzymes and the production of ATP in rat brain and liver mitochondria. Int J Biochem Cell Biol 34:348–357PubMedCrossRefGoogle Scholar
  22. 22.
    Simon N, Papa K, Vidal J, Boulamery A, Bruguerolle B (2003) Circadian rhythms of oxidative phosphorylation: effects of rotenone and melatonin on isolated rat brain mitochondria. Chronobiol Int 20:451–461PubMedCrossRefGoogle Scholar
  23. 23.
    Muhammed H, Kurup CK (1983) Distribution of adriamycin in tissues & subcellular fractions. Indian J Biochem Biophys 20:349–352PubMedGoogle Scholar
  24. 24.
    Malarkodi KP, Balachandar AV, Varlakshmi P (2003) The influence of lipoic acid on adriamycin-induced hyperlipidemic nephrotoxicity in rats. Mol Cell Biochem 247:139–145PubMedCrossRefGoogle Scholar
  25. 25.
    Wallace KB, Starkov AA (2000) Mitochondrial targets of drug toxicity. Annu Rev Pharmacol Toxicol 40:353–388PubMedCrossRefGoogle Scholar
  26. 26.
    Morin D, Barthelemy S, Zini R, Labidalle S, Tillement JP (2001) Curcumin induces the mitochondrial permeability transition pore mediated by membrane protein thiol oxidation. FEBS Lett 495:131–136PubMedCrossRefGoogle Scholar
  27. 27.
    Ji LL, Mitchell EW (1994) Effects of adriamycin on heart mitochondrial function in rested and exercised rats. Biochem Pharmacol 47:877–885PubMedCrossRefGoogle Scholar
  28. 28.
    Zhou YJ, Zhang SP, Liu CW, Cai YQ (2009) The protection of selenium on ROS mediated-apoptosis by mitochondria dysfunction in cadmium-induced LLC-PK(1) cells. Toxicol In Vitro 23:288–294PubMedCrossRefGoogle Scholar
  29. 29.
    Kim TS, Jeong DW, Yun BY, Kim IY (2002) Dysfunction of rat liver mitochondria by selenite: induction of mitochondrial permeability transition through thiol-oxidation. Biochem Biophys Res Commun 294:1130–1137PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Physiology, Faculty of MedicineUniversity of ErciyesKayseriTurkey

Personalised recommendations