Advertisement

Amino Acids

pp 1–7 | Cite as

Protective effect of taurine against doxorubicin-induced cardiotoxicity in rats: echocardiographical and histological findings

  • Veysel Özgür BarışEmail author
  • Esra Gedikli
  • Nilgün Yersal
  • Sevda Müftüoğlu
  • Ayşen Erdem
Original Article
  • 70 Downloads

Abstract

Doxorubicin (DOXO) may cause serious cardiotoxic effects that limit its use as an antineoplastic agent. We aimed to evaluate the protective role of taurine (TAU), a beta amino acid with antioxidant activity, against DOXO-induced cardiotoxicity in a rat model. Thirty-one male Sprague–Dawley rats (300–400 g) were randomized into four groups: control (n = 7, intraperitoneal [ip] saline for 14 days), TAU (n = 8, 150 mg/kg body weight TAU ip for 14 days), DOXO (n = 8, 25 mg/kg body weight DOXO ip on 12th, 13th, and 14th days), and DOXO + TAU (n = 8, TAU for 14 days and DOXO on 12th, 13th, and 14th days). The left ventricular functions were evaluated on 15th day by echocardiography. The heart tissues were then excised for histological evaluation. In DOXO group, left ventricular ejection fraction (LVEF), fractional shortening (FS), and mitral lateral annulus (s') velocity were significantly lower, and the left ventricular end-diastolic and end-systolic diameters (LVEDD, LVESD) were significantly higher than control group (p < 0.05), indicating a significant deterioration in left ventricular functions. However, in comparison to DOXO group, LVESD, LVEDD, LVEF, FS, and s' were significantly improved in DOXO + TAU group (p < 0.05). On histological evaluation, contrary to the normal cellular structure of cardiomyocytes in control and TAU groups, DOXO group showed increased nuclear or cytoplasmic changes and infiltrative cell proliferation (p < 0.001), which were remarkably reduced in DOXO + TAU group (p < 0.001). TAU treatment has a protective effect against DOXO-induced cardiotoxicity on echocardiographical and histological evaluation. For common use of TAU to prevent DOXO-induced cardiotoxicity, our findings should be confirmed by clinical studies.

Keywords

Doxorubicin Cardiotoxicity Taurine Heart failure Malignancy 

Notes

Acknowledgements

We thank to Ersin Fadıllıoğlu MD, Davut Singer MD for the experiments.

Finding

The study was not funded.

Compliance with ethical standards

Conflict of interest

Authors declare no conflicts of interest.

Informed consent

This research involves only animal participants; therefore informed consent was not needed.

References

  1. Agustini FD, Arozal W, Louisa M, et al (2015) Cardioprotection mechanism of mangiferin on doxorubicin-induced rats: focus on intracellular calcium regulation. Pharm Biol 1–9Google Scholar
  2. Angsutararux P, Luanpitpong S, Issaragrisil S (2015) Chemotherapy-induced cardiotoxicity: overview of the roles of oxidative stress. Oxid Med Cell Longev 2015:795602CrossRefGoogle Scholar
  3. Argun M, Uzum K, Sonmez MF, et al (2015) Cardioprotective effect of metformin against doxorubicin cardiotoxicity in rats. Anatol J CardiolGoogle Scholar
  4. Azuma J, Sawamura A, Awata N et al (1985) Therapeutic effect of taurine in congestive heart failure: a double-blind crossover trial. Clin Cardiol 8(5):276–282CrossRefGoogle Scholar
  5. Cantafora A, Blotta I, Rossi SS, Hofmann AF, Sturman JA (1991) Dietary taurine content changes liver lipids in cats. J Nutr 121(10):1522–1528CrossRefGoogle Scholar
  6. Cardinale D, Colombo A, Bacchiani G et al (2015) Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation 131:1981–1988CrossRefGoogle Scholar
  7. Chatterjee K, Zhang J, Honbo N, Karliner JS (2010) Doxorubicin cardiomyopathy. Cardiology 115(2):155–162CrossRefGoogle Scholar
  8. Childs AC, Phaneuf SL, Dirks AJ, 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 Res 62:4592–4598PubMedGoogle Scholar
  9. Guo R, Wu K, Chen J et al (2013) Exogenous hydrogen sulfide protects against doxorubicin-induced inflammation and cytotoxicity by inhibiting p38MAPK/NFkappaB pathway in H9c2 cardiac cells. Cell Physiol Biochem 32(6):1668–1680CrossRefGoogle Scholar
  10. Hanna AD, Lam A, Tham S, Dulhunty AF, Beard NA (2014) Adverse effects of doxorubicin and its metabolic product on cardiac RyR2 and SERCA2A. Mol Pharmacol 86(4):438–449CrossRefGoogle Scholar
  11. Harada H, Cusack BJ, Olson RD et al (1990) Taurine deficiency and doxorubicin: interaction with the cardiac sarcolemmal calcium pump. Biochem Pharmacol 39(4):745–751CrossRefGoogle Scholar
  12. Ito T, Muraoka S, Takahashi K, Fujio Y, Schaffer SW, Azuma J (2009) Beneficial effect of taurine treatment against doxorubicin-induced cardiotoxicity in mice. Adv Exp Med Biol 643:65–74CrossRefGoogle Scholar
  13. Li YT, Maskos K, Chou CW, Cole RB, Li SC (2003) Presence of an unusual GM2 derivative, taurine-conjugated GM2, in Tay-Sachs brain. J Biol Chem 278(37):35286–35291CrossRefGoogle Scholar
  14. Narýn F, Demýr F, Akgün H et al (2004) Doxorubicin-induced experimental cardiotoxicity and effect of pentoxphylline on cardiotoxicity. Turk Kardiyol Dern Ars 32(5):279–287Google Scholar
  15. Pai VB, Nahata MC (2000) Cardiotoxicity of chemotherapeutic agents: incidence, treatment and prevention. Drug Saf 22(4):263–302CrossRefGoogle Scholar
  16. Rapundalo ST (1998) Cardiac protein phosphorylation: functional and pathophysiological correlates. Cardiovasc Res 38(3):559–588CrossRefGoogle Scholar
  17. Razmaraii N, Babaei H, Nayebi AM, Asadnasab G, Helan JA, Azarmi Y (2015) Cardioprotective effect of phenytoin on doxorubicin-induced cardiac toxicity in a rat model. J Cardiovasc PharmacolGoogle Scholar
  18. Renu K, Abilash VG, Tirupathi Pichiah PB, Arunachalam S (2018) Molecular mechanism of doxorubicin-induced cardiomyopathy—an update. Eur J Pharmacol 818:241–253CrossRefGoogle Scholar
  19. Rochette L, Guenancia C, Gudjoncik A et al (2015) Anthracyclines/trastuzumab: new aspects of cardiotoxicity and molecular mechanisms. Trends Pharmacol Sci 36(6):326–348CrossRefGoogle Scholar
  20. Saad SY, Najjar TA, Al-Rikabi AC (2001) The preventive role of deferoxamine against acute doxorubicin-induced cardiac, renal and hepatic toxicity in rats. Pharmacol Res 43(3):211–218CrossRefGoogle Scholar
  21. Saleme B, Gurtu V, Zhang Y et al (2019) Tissue-specific regulation of p53 by PKM2 is redox dependent and provides a therapeutic target for anthracycline-induced cardiotoxicity. Sci Transl Med 11(478)Google Scholar
  22. Schaffer SW, Azuma J, Mozaffari M (2009) Role of antioxidant activity of taurine in diabetes. Can J Physiol Pharmacol 87(2):91–99CrossRefGoogle Scholar
  23. Schaffer SW, Jong CJ, Ramila KC, Azuma J (2010) Physiological roles of taurine in heart and muscle. J Biomed Sci 17(Suppl 1):S2CrossRefGoogle Scholar
  24. Shiny KS, Kumar SH, Farvin KH, Anandan R, Devadasan K (2005) Protective effect of taurine on myocardial antioxidant status in isoprenaline-induced myocardial infarction in rats. J Pharm Pharmacol 57(10):1313–1317CrossRefGoogle Scholar
  25. Vejpongsa P, Yeh ET (2014) Prevention of anthracycline-induced cardiotoxicity: challenges and opportunities. J Am Coll Cardiol 64(9):938–945CrossRefGoogle Scholar
  26. Wang Y, Mei X, Yuan J, Lu W, Li B, Xu D (2015) Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats. Toxicol Appl Pharmacol 289(1):1–11CrossRefGoogle Scholar
  27. Wang J, Qi C, Liu L et al (2018) Taurine protects primary neonatal cardiomyocytes against apoptosis induced by hydrogen peroxide. Int Heart J 59(1):190–196CrossRefGoogle Scholar
  28. Yeh ET, Bickford CL (2009) Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol 53(24):2231–2247CrossRefGoogle Scholar
  29. Zhang S, Meng T, Liu J, Zhang X, Zhang J (2015) Cardiac protective effects of dexrazoxane on animal cardiotoxicity model induced by anthracycline combined with trastuzumab is associated with upregulation of calpain-2. Medicine (Baltimore) 94(4):e445CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of CardiologyGülhane Research and Education HospitalAnkaraTurkey
  2. 2.Department of Physiology, Faculty of MedicineHacettepe UniversityAnkaraTurkey
  3. 3.Department of Histology, Faculty of MedicineHacettepe UniversityAnkaraTurkey

Personalised recommendations