DOKSORUBİSİN KARDİYOTOKSİSİTESİNİN OLUŞUMU VE ÖNLENMESİ

Zeynep Erdoğmuş Özgen

doi:10.52538/iduhes.827754

DOKSORUBİSİN KARDİYOTOKSİSİTESİNİN OLUŞUMU VE ÖNLENMESİ

Öz

Yüksek antineoplastik aktiviteleri nedeniyle onkolojide en sık kullanılan antrasiklinler arasında yer alan doksorubisin; göğüs, over, testis, tiroid, akciğer kanserlerinde ve birçok sarkomun tedavisinde klinik uygulaması olan önemli ilaçlardan biridir. Ancak doksorubisinin klinik kullanımını kısıtlayan önemli ve ciddi kardiotoksik yan etkisi vardır. Bu derlemede kardiotoksik etki mekanizmasının araştırılması amaçlandı. Araştırma sonucunda kardiotoksisite oluşumunda; nükleik asit ve protein sentezinin inhibisyonu, vazoaktif aminlerin salınımı, mitokondriyal membran potansiyelinde kayıp ve elektron trasport zincirinin inhibisyonu, adrenerjik fonksiyonlardaki değişiklikler, adenilat siklaz, Na+-K+ ATPaz ve Ca+ ATPaz aktivitelerinin azalması gibi mekanizmalar etkili olsa da oksidatif stres ve apoptozisin asıl etken olduğu görülmüştür. Doksorubisinin oluşturduğu kardiotoksisiteyi azaltmaya yönelik koruyucu maddeler araştırmalarda kullanılmış olsa da bu maddelerin klinikte kullanımları yeterli düzeylere ulaşılabilmiş değildir. Yapılan literatür taraması sonucunda, Doksorubisinin oluşturduğu kardiotoksisiteyi azaltmaya yönelik daha ayrıntılı çalışmaların yapılması gerektiği kanaatine varılmıştır.

Anahtar Kelimeler

Destekleyen Kurum

YOK

Proje Numarası

YOK

Kaynakça

Al-Majed, AA., Gado, AM., Al-Shabanah, OA., Mansour, MA.(2002). Alpha-lipoic acid ameliorates myocardial toxicity induced by Doksorubisin. Pharmacol Res,46:499-503.
Altieri, P., Spallarossa, P., Barisione, C., Garibaldi, S., Garuti, A., Fabbi, P., Ghigliotti, G., Brunelli, C.(2012). Inhibition of Doksorubisin-Induced Senescence by PPARδ Activation Agonists in Cardiac Muscle Cells: Cooperation between PPARδ and Bcl6. PLoS One, 7(9):e46126. doi: 10.1371/journal.pone.0046126.
Bates, SE., Rosing, DR., Lobins, RL.(2006). Challenges of evaluating the cardiac effects of anticancer agents. Clin Cancer Res, 12: 3871.
Berthiaume, J., Wallace, K. (2007). Adriamycin-induced oxidative mitochondrial cardiotoxicity. Cell Biol. Toxicol. 23, 15–25. Billingham, ME., Mason, JW., Bristow, MR., Daniels, JR.(1978). Antracycline cardiomyopathy monitered by morphologic changes. Cancer Treat Rep, 62: 865.
Bristow, M., Sageman, W.S, Scott, R.H., Billingham, M.E., Bowden, R.E., Kernoff, R.S., Snidow, I.H., Daniel, J.R.(1980). Acute and chronic cardiovascular effects of doxorubicin in the dog: The cardiovascular pharmacology of drug-induced histamine release. J. Cardiovasc. Pharmacol., 2; 487-515.
Carvalho, RA., Sousa, RP., Cadete, VJ., Lopaschuk, GD., Palmeira, CM., Bjork, JA. et al.(2010). Metabolic remodeling associated with subchronic doxorubicin cardiomyopathy. Toxicology, 270: 92–98.
Childs, A.C., Phaneuf, S. L., Dirks, A. J., Phillips, T., & Leeuwenburgh, C.(2002). Doxorubicin treatment in vivo causes cytochrome C release and cardiomyocyte apoptosis, as well as increased mitochondrial efficiency, superoxide dismutase activity, and Bcl-2: Bax ratio. Cancer research, 62(16), 4592-4598.
Cortes-Funes, H., Coronado C. ( 2007). Role of anthracyclines in the era of targeted therapy. Cardiovasc Toxicol, 7:56–60.

Cummings, J., Willmott, N., Smyth, J.(1991). The molecular pharmacology of doxorubicin in vivo. Eur J Cancer, 27: 532-535.
Deng, S., Kruger, A., Kleschyov, AL., Kalinowski, L., Daiber, A., Wojnowski, L.(2007). Gp91phox containing NAD(P)H oxidase increases superoxide formation by doxorubicin and NADPH. Free Radic Biol Med, 42: 466–473.
Deng, S., Yan, T., Jendrny, C., Nemecek, A., Vincetic, M., Gödtel-Armbrust, U., & Wojnowski, L. (2014). Dexrazoxane may prevent doxorubicin-induced DNA damage via depleting both topoisomerase II isoforms. BMC cancer, 14(1), 842.
Fogli, S., Nieri, P., Breschi, M.C. (2004). The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage. FASEB J. 18,664–675.
Fridovich I.(1995). Superoxide radical and superoxide dismutases. Annu. Rev. Biochem.64, 97–112.
Galluzzi, L., Joza, N., Tasdemir, E., et al.(2009). No death without life: vital function of apoptotic effectors. Cell Death Differ, 16:1093–1107.
Gilleron, M., Marechal, X., Montaigne, D., Franczak, J., Neviere, R., Lancel, S.(2009). NADPH oxidases participate to doxorubicin-induced cardiac myocyte apoptosis. Biochem Biophys Res Commun, 388: 727–731.
Giorgio, M., Menna, P., Salvatorelli, E., Cairo, G., Gianni, L.(2004). Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity. Pharmacol Rev, 56:185-229.
Goffart, S., von Kleist-Retzow, J.-C., Wiesner, R.J.(2004). Regulation of mitochondrial proliferation in the heart: power-plant failure contributes to cardiac failure in hypertrophy. Cardiovasc. Res. 64, 198–207.
Goodman Gilman A. (2006). Goodman & Gilman's The Pharmacological Basis of Therapeutics. Eleventh edition. McGraw-Hill Medical Publishing Division, chapter: 51; 1358-1359.
Goormaghtigh, E., Chatelain, P., Caspers, J., Ruysschaert, JM.(1980). Evidence of a complex between adriamycin derivatives and cardiolipin: possible role in cardiotoxicity. Biochem Pharmacol, 29: 3003–3310.
Gu, J., Song, ZP., Gui, DM., Hu, W., Chen, YG., Zhang, DD.(2012). Resveratrol Attenuates Doksorubisin-Induced Cardiomyocyte Apoptosis in Lymphoma Nude Mice by Heme Oxygenase-1 Induction. Cardiovasc Toxicol., 12(4):341-349. Horenstein, MS., Vander Heide, RS., L'Ecuyer, TJ.(2000). Molecular basis of anthracyclineinduced cardiotoxicity and its prevention. Mol Genet Metab, 71: 436–444.
Huber, SA.(1990). Doxorubicin-induced alterations incultured myocardial cells stimulate cytolytic T-lymphocyte responses. Am J Pathol, 137: 449-456.
Ichikawa, Y., Ghanefar, M., Bayeva, M., Wu, R., Khechaduri, A., Prasad, S.V.N., Mutharasan, R.K., Naik, T.J., Ardehali, H. (2014). Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation. J. Clin. Investig. 124(2), 617-630.
Jain D. (2000). Cardiotoxicity of doxorubicin and other anthracycline derivatives. J Nucl Cardiol, 7: 53–62.
Janbabai, G., Nabati, M., Faghihinia, M., Azizi, S., Borhani, S., & Yazdani, J. (2017). Effect of enalapril on preventing anthracycline-induced cardiomyopathy. Cardiovascular toxicology, 17(2), 130-139.
Jordon, MA.(2002). Anti-cancer agents. Cur Med Chem, 2:1–17.
Kim, S. Y., Kim, S. J., Kim, B. J., Rah, S. Y., Chung, S. M., Im, M. J., & Kim, U. H. (2006). Doxorubicin-induced reactive oxygen species generation and intracellular Ca2+ increase are reciprocally modulated in rat cardiomyocytes. Experimental & Molecular Medicine, 38(5), 535-545.
L’Ecuyer T, Sanjeev S, Thomas R et al (2006) DNA damage is an early event in doxorubicin-induced cardiac myocyte death. Am J Physiol Heart Circ Physiol 291:H1273–H1280.
Lebrecht, D., Walker, UA. (2007). Role of mtDNA lesions in anthracycline cardiotoxicity. Cardiovasc Toxicol 7:108–113.
Li, J., Wang, P. Y., Long, N. A., Zhuang, J., Springer, D. A., Zou, J., ...&Hwang, P. M. (2019). p53 prevents doxorubicin cardiotoxicity independently of its prototypical tumor suppressor activities. Proceedings of the National Academy of Sciences, 116(39), 19626-19634.
Liu, B., Bai,, QX., Chen, XQ., Gao, GX., Gu, HT.(2007). Effect of curcumin on expression of survivin, Bcl-2 and Bax in human multiple myeloma cell line. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 15: 762–766.
Ma, J., Wang, Y., Zheng, D., Wei, M., Xu, H., Peng, T.(2013). Rac1 signalling mediates Doksorubisin-induced cardiotoxicity through both reactive oxygen species-dependent and-independent pathways. Cardiovasc Res, 1;97(1):77-87.
Minotti, G., Recalcati, S., Menna, P., et al.(2004). Doxorubicin cardiotoxicity and the control of iron metabolism: quinone-dependent and independent mechanisms. Methods Enzymol, 378: 340-361.
Moens, AL., Leyton-Mange, JS., Niu, X., Yang, R., Cingolani, O., Arkenbout, EK. et al.(2009). Adverse ventricular remodeling and exacerbated NOS uncoupling from pressure-overload in mice lacking the beta3-adrenoreceptor. J Mol Cell Cardiol, 47: 576–585.
Morishima, I., Okumura, K., Matsui, H. et al. (1999). Zinc accumulation in adriamycin-induced cardiomyopathy in rats: effects of cardioprotective antioxidant. J Pineal Res, 26: 204-210.
Mukhopadhyay, P., Rajesh, M., Bátkai, S., Kashiwaya, Y., Hasko, G., Liaudet, L., ... & Pacher, P. (2009). Role of superoxide, nitric oxide, and peroxynitrite in doxorubicin-induced cell death in vivo and in vitro. American Journal of Physiology-Heart and Circulatory Physiology, 296(5), H1466-H1483.
Nabati, M., Janbabai, G., Baghyari, S., Esmaili, K., & Yazdani, J. (2017). Cardioprotective effects of carvedilol in inhibiting doxorubicin-induced cardiotoxicity. Journal of Cardiovascular Pharmacology, 69(5), 279-285.
Neilan, TG., Blake, SL., Ichinose, F., Raher, MJ., Buys, ES., Jassal, DS.(2007). Disruption of nitric oxide synthase 3 protects against the cardiac injury, dysfunction, and mortality induced by doxorubicin. Circulation, 116: 506–514.
Nishiyama, K., Yasue, H., Moriyama, Y. et al.(2001). Acute effects of melatonin administration on cardiovascular autonomic regulation in healty men. Am Heart J, 141: 149.
Nitobe, J., Yamaguchi, S., Okuyama, M., Nozaki, N., Sata, M., Miyamoto, T., et al. (2003). Reactive oxygen species regulate FLICE inhibitory protein (FLIP) and susceptibility to Fas mediated apoptosis in cardiac myocytes. Cardiovasc Res, 57: 119–128.
Octavia, Y., Tocchetti, C.G., Gabrielson, K.L., Janssens, S., Crijns, H.J., Moens, A.L. (2012). Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeutic strategies. J. Mol. Cell. Cardiol. 52, 1213–1225.
Oliveira, PJ., Wallace, K.B. (2006). Depletion of adenine nucleotide translocator protein in heart mitochondria from doxorubicin-treated rats-relevance for mitochondrial dysfunction. Toxicology, 220; 160-168.
Olson, R.D., Mushlin, P.S. (1990). Doxorubicin cardiotoxicity: analysis of prevailing hypotheses. FASEB J. 4, 3076–3086.
Outomuro, D., Grana, DR., Azzato, F., Milei J.(2007). Adriamycine – induced myocardial toxicity: New solutions for an old problem? Int J Cardiol, 12: 117(1):6-15.
Ozgen, Z. E., Erdinc, M., Akkoc, H., & Kelle, I. (2016). Protective effects of melatonin on doxorubicin induced cardiotoxicity in isolated rat heart. Eastern Journal of Medicine, 21(3), 119.
Pacher, P., Liaudet, L., Bai, P., et al. (2003). Potent metalloporphyrin peroxynitrite decomposition catalyst protects against the development of doxorubicin-induced cardiac dysfunction. Circulation, 107: 896–904.
Pani, G., Bedogni, B., Anzevino, R., Colavitti, R., Palazzotti, B., Borrello, S., Galeotti, T. (2000). Deregulated manganese superoxide dismutase expression and resistance to oxidative injury in p53-deficient cells. Cancer Res. 60, 4654–4660.
Pereira, G.C., Silva, A.M., Diogo, C.V., Carvalho, F.S., Monteiro, P., Oliveira, P.J.(2011). Drug-induced cardiac mitochondrial toxicity and protection: from doxorubicin to carvedilol. Curr. Pharm. Des. 17, 2113–2129.
Reiter, RJ. (1992). The aging pineal and its physiological consequences. BioEssay, 14: 169- 175.
Sacco, G., Bigioni, M., Lopez, G., Evangelista, S., Manzini, S., Maggi, C.A.(2009). ACE inhibition and protection from doxorubicin-induced cardiotoxicity in the rat. Vasc. Pharmacol. 50, 166–170.
Sahna, E., Parlakpinar, H., Ozturk, F., Ozer, M.K., Ozugurlu, F., Acet, A. (2003).Melatonin protects against myocardial doxorubicin toxicity in rats: Role of physiological concentrations. J Pineal Res,35: 257-261.
Schlame, M., Rua, D., Greenberg, ML. (2000). The biosynthesis and functional role of cardiolipin. Prog Lipid Res, 39: 257–288.
Schwebe, M., Ameling, S., Hammer, E., Monzel, J. V., Bonitz, K., Budde, S., ... & Poesch, A. (2015). Protective effects of endothelin receptor A&B inhibitors against doxorubicin-induced cardiomyopathy. Biochemical pharmacology, 94(2), 109-129.
Shi, Y., Moon, M., Dawood, S., McManus, B., Liu, P.(2011). Mechanisms and management of doxorubicin cardiotoxicity. Herz 36, 296–305.
Simunek, T., Sterba, M., Popelova, O., Adamcova, M., Hrdina, R., Gersl, V. (2009). Anthracycline induced cardiotoxicity: overview of studies examining the roles of oxidative stress and free cellular iron. Pharmacol Rep, 61: 154–171.
Singal, PK., Iliskovic N.(1998). Doxorubicin-induced cardiomyopathy. N Engl J Med, 339: 900.
Sishi, BJ., Loos, B., Van Rooyen, J., Engelbrecht, AM. (2013). Autophagy upregulation promotes survival and attenuates Doksorubisin-induced cardiotoxicity. Biochem Pharmacol., 1;85(1):124-134.
Suliman, HB., Carraway, MS., Ali, AS., Reynolds, CM., Welty-Wolf, KE., Piantadosi, CA. (2007). The CO/HO system reverses inhibition of mitochondrial biogenesis and prevents murine doxorubicin cardiomyopathy. J Clin Invest, 117: 3730–3741.
Thorn, CF., Oshiro, C., Marsh, S., Hernandez-Boussard, T., McLeod, H., Klein, TE., Altman, RB. (2011). Doxorubicin pathways: pharmacodynamics and adverse effects, Pharmacogenet. Genomics, 21:440–446.
Tong, J., Ganguly, P.K, Singal, P.K. (1991). Myocardial adrenergic changes at two stages of heart failure due to adriamycin treatment in rats. Am. J. Physiol, 260; 909-916.
Ueno, M., Kakinuma, Y., Yuhki, K., Murakoshi, N., Iemitsu, M., Miyauchi, T. et al. (2006). Doxorubicin induces apoptosis by activation of caspase-3 in cultured cardiomyocytes in vitro and rat cardiac ventricles in vivo. J Pharmacol Sci., 101: 151–158.
Vasquez-Vivar, J., Martasek, P., Hogg, N., Masters, BS., Pritchard Jr, KA., Kalyanaraman, B. (1997). Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin. Biochemistry, 36: 11293–11297.
Walker, J. R., Sharma, A., Lytwyn, M., Bohonis, S., Thliveris, J., Singal, P. K., & Jassal, D. S. (2011). The cardioprotective role of probucol against anthracycline and trastuzumab-mediated cardiotoxicity. Journal of the American Society of Echocardiography, 24(6), 699-705.
Wallace, KB. (2007). Adriamycin-induced interference with cardiac mitochondrial calcium homeostasis. Cardiovasc Toxicol 7:101–107.
Weiss RB. (1992). The anthracyclines: will we ever find a better doxorubicin? Semin Oncol, 19:670–686.
Xu, MF., Tang, PL., Qian, ZM. (2001). Ashraf M. Effects by doxorubicin on the myocardium are mediated by oxygen free radicals. Life Sci, 68: 889–901.
Ying, W. (2008). NAD+/NADH and NADP+/NADPH in cellular functions and cell death: regulation and biological consequences. Antioxid Redox Signal, 10: 179-206.
Youn, HJ., Kim, HS., Jeon, MH., Lee, JH., Seo, YJ., Lee, YJ. et al. (2005). Induction of caspase independent apoptosis in H9c2 cardiomyocytes by adriamycin treatment. Mol Cell Biochem., 270: 13–19.
Yu, X., Ruan, Y., Huang, X., Dou, L., Lan, M., Cui, J., ... & Sun, S. (2020). Dexrazoxane ameliorates doxorubicin-induced cardiotoxicity by inhibiting both apoptosis and necroptosis in cardiomyocytes. Biochemical and Biophysical Research Communications, 523(1), 140-146.
Zhang, S., Liu, X., Bawa-Khalfe, T., Lu, L. S., Lyu, Y. L., Liu, L. F., & Yeh, E. T. (2012). Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nature medicine, 18(11), 1639-1642.
Zhao, L., Zhang, B. (2017). Doxorubicin induces cardiotoxicity through upregulation of death receptors mediated apoptosis in cardiomyocytes. Sci. Rep. 7, 44735.
Zucchi, R., Danesi R. (2003). Cardiac toxicity of antineoplastic anthracyclines. Curr Med Chem,3: 151-171.

Ayrıntılar

Birincil Dil

Türkçe

Konular

Eczacılık ve İlaç Bilimleri

Bölüm

Derleme

Yazarlar

Zeynep Erdoğmuş Özgen ^*
0000-0001-6607-836X
Türkiye

Yayımlanma Tarihi

30 Mayıs 2021

Gönderilme Tarihi

18 Kasım 2020

Kabul Tarihi

3 Mayıs 2021

Yayımlandığı Sayı

Yıl 2021 Cilt: 4 Sayı: 1

DOI

https://doi.org/10.52538/iduhes.827754

IZ

https://izlik.org/JA59FE32RX

Kaynak Göster

RIS / Bibtex

APA

Erdoğmuş Özgen, Z. (2021). DOKSORUBİSİN KARDİYOTOKSİSİTESİNİN OLUŞUMU VE ÖNLENMESİ. Izmir Democracy University Health Sciences Journal, 4(1), 1-15. https://doi.org/10.52538/iduhes.827754

AMA

1.Erdoğmuş Özgen Z. DOKSORUBİSİN KARDİYOTOKSİSİTESİNİN OLUŞUMU VE ÖNLENMESİ. IDUHeS. 2021;4(1):1-15. doi:10.52538/iduhes.827754

Chicago

Erdoğmuş Özgen, Zeynep. 2021. “DOKSORUBİSİN KARDİYOTOKSİSİTESİNİN OLUŞUMU VE ÖNLENMESİ”. Izmir Democracy University Health Sciences Journal 4 (1): 1-15. https://doi.org/10.52538/iduhes.827754.

EndNote

Erdoğmuş Özgen Z (01 Mayıs 2021) DOKSORUBİSİN KARDİYOTOKSİSİTESİNİN OLUŞUMU VE ÖNLENMESİ. Izmir Democracy University Health Sciences Journal 4 1 1–15.

IEEE

[1]Z. Erdoğmuş Özgen, “DOKSORUBİSİN KARDİYOTOKSİSİTESİNİN OLUŞUMU VE ÖNLENMESİ”, IDUHeS, c. 4, sy 1, ss. 1–15, May. 2021, doi: 10.52538/iduhes.827754.

ISNAD

Erdoğmuş Özgen, Zeynep. “DOKSORUBİSİN KARDİYOTOKSİSİTESİNİN OLUŞUMU VE ÖNLENMESİ”. Izmir Democracy University Health Sciences Journal 4/1 (01 Mayıs 2021): 1-15. https://doi.org/10.52538/iduhes.827754.

JAMA

1.Erdoğmuş Özgen Z. DOKSORUBİSİN KARDİYOTOKSİSİTESİNİN OLUŞUMU VE ÖNLENMESİ. IDUHeS. 2021;4:1–15.

MLA

Erdoğmuş Özgen, Zeynep. “DOKSORUBİSİN KARDİYOTOKSİSİTESİNİN OLUŞUMU VE ÖNLENMESİ”. Izmir Democracy University Health Sciences Journal, c. 4, sy 1, Mayıs 2021, ss. 1-15, doi:10.52538/iduhes.827754.

Vancouver

1.Zeynep Erdoğmuş Özgen. DOKSORUBİSİN KARDİYOTOKSİSİTESİNİN OLUŞUMU VE ÖNLENMESİ. IDUHeS. 01 Mayıs 2021;4(1):1-15. doi:10.52538/iduhes.827754

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https://doi.org/10.17343/sdutfd.1198304