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Protective effect of edaravone on adriamycin-induced cardiotoxicity in rats

Yıl 2019, Cilt: 41 Sayı: 1, 10 - 18, 28.03.2019

Hatice Aygün , Serdar Savaş Gül

https://doi.org/10.7197/223.vi.531824
Cited By: 1

Öz

Aim: Adriamycin (ADR) is an antineoplastic drug that
is widely used in chemotherapy but its cardiotoxicity is the most important
side effect that limits the clinical use of this drug. In this study, we
investigated of edaravone (EDO), which is a potent antioxidant, ADR-induced
cardiotoxicity model in rats by electrocardiographic (ECG), biochemical and
scintigraphic methods.

Methods: Twenty-eight adult male
Wistar-Albino rats were randomly separated into four groups; namely control
(CON); Adriamycin (ADR); substance control of edaravone (EDO), edaravone +
adriamycin (EDO+ADR) groups. Cardiotoxicity in rats was induced by adriamycin
injection (cumulative dose:18 mg/kg, intraperitoneal-i.p.-) at an interval of
24 hours (h) on the 5th, 6th and 7th days.
Rats receiving edaravone treatment in the adriamycin group administration
edaravone (30 mg/kg/day, i.p.) for 7 days and were injected with adriamycin (18
mg/kg, i.p.) on 5th, 6th and 7th days.
On the 8th day electrocardiography (ECG), biochemical and
technetium-99m pyrophosphate (99mTc-PYP) scintigraphic parameters
were assessed.

 Results: ADR
induction caused changes in the ECG pattern, decreased heartbeat, P wave and
QRS complex duration,  increased both ST-segment amplitude and QT interval
duration (p < 0,001), increase in the biochemical markers [blood urea
nitrogen (BUN), creatine kinase (CK), cardiac troponin T (cTnT)], and
 elevated 99mTc-PYP uptake level (p < 0,001). EDO
treatment prevented all the parameters of ADR-induced cardiotoxicity in rats,
by significantly decreased all ADR-associated conduction abnormalities in
ECG (p < 0.001), decreased 99mTc-PYP uptake (p <
0.001) and serum BUN, CK and cTnT, (p < 0.001).







Conclusions: Our data demonstrate
that EDO has cardioprotective effects on DOX-induced cardiotoxicity. At the
same time, this study suggested that 99mTc-PYP may be using as
a non-invasive method for the early diagnosis of ADR-induced cardiotoxicity.

Anahtar Kelimeler

Adriamycin cardiotoxicity edaravone 99mTc-PYP ECG

Kaynakça

  • Damiani RM, Moura DJ, Viau CM, et al. Pathways of cardiac toxicity: comparison between chemotherapeutic drugs doxorubicin and mitoxantrone. Arch Toxicol. 2016;90:2063-2076.
  • Wang L, Zhang X, Chan JY, et al. A novel danshensu derivative prevents cardiac dysfunction and improves the chemotherapeutic efficacy of doxorubicin in breast cancer cells. J Cell Biochem. 2016;117:94-105.
  • Castells MC, Tennant NM, Sloane DE, et al. Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases, J Allergy Clin Immunol. 2008;122(3):574-580.
  • Cappetta D, Rossi F, Piegari E, et al. Doxorubicin targets multiple players: a new view of an old problem. Pharmacol Res. 2018;127:4-14.
  • Anjos Ferreira AL, Russell RM, Rocha N, et al. Effect of lycopene on doxorubicin-induced cardiotoxicity: an echocardiographic, histological and morphometrical assessment. Basic Clin Pharmacol Toxicol. 2007;101:16-24.
  • Swamy AH, Wangikar U, Koti BC, et al. Cardioprotective effect of ascorbic acid on doxorubicin-induced myocardial toxicity in rats. Indian J Pharmacol. 2011;43(5):507-511.
  • Aygun H, Gul SS. Effects of melatonin and agomelatine on doxorubicin induced anxiety and depression-like behaviors in rats. Medical Science and Discovery. 2018;5(7):253-259.
  • Gül SS, Aygün H. Cardioprotective effect of vitamin D and melatonin on doxorubicin-induced cardiotoxicity in rat model: an electrocardiographic, scintigraphic and biochemical study. The European Res J. 2018. doi: 10.18621/eurj.410029.
  • Aygun H, Gul SS. Protective effect of melatonin and agomelatine on adriamycin-induced nephrotoxicity in rat model: a renal scintigraphy and biochemical study. Bratisl Med J. 2019;120(2):119-123.
  • The Edaravone Acute Infarction Study Group. Effect of a novel free radical scavenger, edaravone (MCI-186), on acute brain infarction. Randomized, placebo-controlled, double-blind study at multicenters. Cerebrovasc Dis. 2003;15:222-229.
  • Tokumaru O, Shuto Y, Ogata K, et al. Dose-dependency of multiple free radical-scavenging activity of edaravone. J Surg Res. 2018;228:147-153.
  • Abe S, Kirima K, Tsuchiya K, et al. The reaction rate of edaravone (3-methyl-1-phenyl-2-pyrazolin5-one (MCI-186)) with hydroxyl radical. Chem Pharm Bull. (Tokyo) 2004;52(2):186-191.
  • Suzuki J, Yanagisawa A, Shigeyama T, et al. Early detection of anthracycline-induced cardiotoxicity by radionuclide angiocardiography. Angiology 1999;50:37-45.
  • Koti BC, Nagathan S, Vishwanathswamy A, et al. Cardioprotective effect of Vedic Guard against doxorubicin-induced cardiotoxicity in rats: A biochemical, electrocardiographic, and histopathological study. Pharmacogn Mag. 2013;9:176-181.
  • Bhatt L, Joshi V. Mangifera indica L. leaf extract alleviates doxorubicin induced cardiac stress. J Intercult Ethnopharmacol. 2017;6:284-289.
  • Bilginoglu A, Aydın D, Ozsoy S, Aygün H. Protective effect of melatonin on adriamycin-induced cardiotoxicity in rats. Turk Kardiyol Dern Ars 2014;42(3):265-273.
  • Zhang S, Liu X, Bawa-Khalfe T, et al. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med. 2012;18:1639-1642.
  • Renu K, Abilash VG, P B TP, et al. Molecular mechanism of doxorubicin-induced cardiomyopathy–An update. Eur J Pharmacol. 2018;818:241-253.
  • Xin Y, Zhan S, Gu L, et al. Electrocardiographic and biochemical evidence for the cardioprotective effect of antioxidants in acute doxorubicin-induced cardiotoxicity in the beagle dogs. Biol Pharm Bull. 2011;34(10):1523-1526.
  • Wang S, Konorev EA, Kotamraju S, et al. Doxorubicin induces apoptosis in normal and tumor cells via distinctly different mechanisms. intermediacy of H(2)O(2)- and p53-dependent pathways. J Biol Chem. 2004;279:25535-25543.
  • Peng X, Chen B, Lim CC, Sawyer DB. The cardiotoxicology of anthracycline chemotherapeutics: translating molecular mechanism into preventative medicine. Mol Interv. 2005;5(3):163-171.
  • Wakade AS, Shah AS, Kulkarni MP, Juvekar AR. Protective effect of Piper longum L. on oxidative stress induced injury and cellular abnormality in adriamycin induced cardiotoxicity in rats. Indian J Exp Biol. 2008;46:528-533.
  • Hassan MQ, Akhtar MS, Akhtar M, et al. Edaravone, a potent free radical scavenger and a calcium channel blocker attenuate isoproterenol induced myocardial infarction by suppressing oxidative stress, apoptotic signaling and ultrastructural damage. Ther Adv Cardiovasc Dis. 2016;10(4):214-223.
  • Kikuchi K, Tancharoen S, Takeshige N, et al. The efficacy of edaravone (radicut), a free radical scavenger, for cardiovascular disease. Int J Mol Sci. 2013;14(7):13909-13930.
  • Im GJ, Chang J, Lee S, et al. Protective role of edaravone against cisplatin-induced ototoxicity in an auditory cell line. Hear Res. 2015;330:113-118.
  • Mochizuki T, Murase K, Higashino H, et al. Ischemic "memory image" in acute myocardial infarction of 123I-BMIPP after reperfusion therapy: a comparison with 99mTc-pyrophosphate and 201Tl dual-isotope SPECT. Ann Nucl Med. 2002;16(8):563-568.
  • Einstein AJ, Shuryak I, Castano A, et al. Estimating cancer risk from 99mTc pyrophosphate imaging for transthyretin cardiac amyloidosis. J Nucl Cardiol. 2018. doi: 10.1007/s12350-018-1307-7.
  • Isoda H, Itagaki Y, Nomura N, et al. Usefulness of dual SPECT with Tc-99m pyrophosphate and Tl-201 to predict further events after acute myocardial infarction with single-vessel coronary artery disease. Clin Nucl Med. 1999;24(4):227-231.
  • Okuda K, Nohara R, Fujita M, et al. Technetium-99m-pyrophosphate uptake as an indicator of myocardial injury without infarct. J Nucl Med 1994;35:1366-1370.
  • Affleck DG, Edelman L, Morris SE, Saffle JR. Assessment of tissue viability in complex extremity injuries: utility of the pyrophosphate nuclear scan. J Trauma. 2001;50:263-269.
  • Chang HR, Kao CH, Lian JD, et al. Evaluation of the severity of traumatic rhabdomyolysis using technetium-99m pyrophosphate scintigraphy. Am J Nephrol. 2001;21:208-214.

Yıl 2019, Cilt: 41 Sayı: 1, 10 - 18, 28.03.2019

Hatice Aygün , Serdar Savaş Gül

https://doi.org/10.7197/223.vi.531824
Cited By: 1

Öz


Kaynakça

  • Damiani RM, Moura DJ, Viau CM, et al. Pathways of cardiac toxicity: comparison between chemotherapeutic drugs doxorubicin and mitoxantrone. Arch Toxicol. 2016;90:2063-2076.
  • Wang L, Zhang X, Chan JY, et al. A novel danshensu derivative prevents cardiac dysfunction and improves the chemotherapeutic efficacy of doxorubicin in breast cancer cells. J Cell Biochem. 2016;117:94-105.
  • Castells MC, Tennant NM, Sloane DE, et al. Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases, J Allergy Clin Immunol. 2008;122(3):574-580.
  • Cappetta D, Rossi F, Piegari E, et al. Doxorubicin targets multiple players: a new view of an old problem. Pharmacol Res. 2018;127:4-14.
  • Anjos Ferreira AL, Russell RM, Rocha N, et al. Effect of lycopene on doxorubicin-induced cardiotoxicity: an echocardiographic, histological and morphometrical assessment. Basic Clin Pharmacol Toxicol. 2007;101:16-24.
  • Swamy AH, Wangikar U, Koti BC, et al. Cardioprotective effect of ascorbic acid on doxorubicin-induced myocardial toxicity in rats. Indian J Pharmacol. 2011;43(5):507-511.
  • Aygun H, Gul SS. Effects of melatonin and agomelatine on doxorubicin induced anxiety and depression-like behaviors in rats. Medical Science and Discovery. 2018;5(7):253-259.
  • Gül SS, Aygün H. Cardioprotective effect of vitamin D and melatonin on doxorubicin-induced cardiotoxicity in rat model: an electrocardiographic, scintigraphic and biochemical study. The European Res J. 2018. doi: 10.18621/eurj.410029.
  • Aygun H, Gul SS. Protective effect of melatonin and agomelatine on adriamycin-induced nephrotoxicity in rat model: a renal scintigraphy and biochemical study. Bratisl Med J. 2019;120(2):119-123.
  • The Edaravone Acute Infarction Study Group. Effect of a novel free radical scavenger, edaravone (MCI-186), on acute brain infarction. Randomized, placebo-controlled, double-blind study at multicenters. Cerebrovasc Dis. 2003;15:222-229.
  • Tokumaru O, Shuto Y, Ogata K, et al. Dose-dependency of multiple free radical-scavenging activity of edaravone. J Surg Res. 2018;228:147-153.
  • Abe S, Kirima K, Tsuchiya K, et al. The reaction rate of edaravone (3-methyl-1-phenyl-2-pyrazolin5-one (MCI-186)) with hydroxyl radical. Chem Pharm Bull. (Tokyo) 2004;52(2):186-191.
  • Suzuki J, Yanagisawa A, Shigeyama T, et al. Early detection of anthracycline-induced cardiotoxicity by radionuclide angiocardiography. Angiology 1999;50:37-45.
  • Koti BC, Nagathan S, Vishwanathswamy A, et al. Cardioprotective effect of Vedic Guard against doxorubicin-induced cardiotoxicity in rats: A biochemical, electrocardiographic, and histopathological study. Pharmacogn Mag. 2013;9:176-181.
  • Bhatt L, Joshi V. Mangifera indica L. leaf extract alleviates doxorubicin induced cardiac stress. J Intercult Ethnopharmacol. 2017;6:284-289.
  • Bilginoglu A, Aydın D, Ozsoy S, Aygün H. Protective effect of melatonin on adriamycin-induced cardiotoxicity in rats. Turk Kardiyol Dern Ars 2014;42(3):265-273.
  • Zhang S, Liu X, Bawa-Khalfe T, et al. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med. 2012;18:1639-1642.
  • Renu K, Abilash VG, P B TP, et al. Molecular mechanism of doxorubicin-induced cardiomyopathy–An update. Eur J Pharmacol. 2018;818:241-253.
  • Xin Y, Zhan S, Gu L, et al. Electrocardiographic and biochemical evidence for the cardioprotective effect of antioxidants in acute doxorubicin-induced cardiotoxicity in the beagle dogs. Biol Pharm Bull. 2011;34(10):1523-1526.
  • Wang S, Konorev EA, Kotamraju S, et al. Doxorubicin induces apoptosis in normal and tumor cells via distinctly different mechanisms. intermediacy of H(2)O(2)- and p53-dependent pathways. J Biol Chem. 2004;279:25535-25543.
  • Peng X, Chen B, Lim CC, Sawyer DB. The cardiotoxicology of anthracycline chemotherapeutics: translating molecular mechanism into preventative medicine. Mol Interv. 2005;5(3):163-171.
  • Wakade AS, Shah AS, Kulkarni MP, Juvekar AR. Protective effect of Piper longum L. on oxidative stress induced injury and cellular abnormality in adriamycin induced cardiotoxicity in rats. Indian J Exp Biol. 2008;46:528-533.
  • Hassan MQ, Akhtar MS, Akhtar M, et al. Edaravone, a potent free radical scavenger and a calcium channel blocker attenuate isoproterenol induced myocardial infarction by suppressing oxidative stress, apoptotic signaling and ultrastructural damage. Ther Adv Cardiovasc Dis. 2016;10(4):214-223.
  • Kikuchi K, Tancharoen S, Takeshige N, et al. The efficacy of edaravone (radicut), a free radical scavenger, for cardiovascular disease. Int J Mol Sci. 2013;14(7):13909-13930.
  • Im GJ, Chang J, Lee S, et al. Protective role of edaravone against cisplatin-induced ototoxicity in an auditory cell line. Hear Res. 2015;330:113-118.
  • Mochizuki T, Murase K, Higashino H, et al. Ischemic "memory image" in acute myocardial infarction of 123I-BMIPP after reperfusion therapy: a comparison with 99mTc-pyrophosphate and 201Tl dual-isotope SPECT. Ann Nucl Med. 2002;16(8):563-568.
  • Einstein AJ, Shuryak I, Castano A, et al. Estimating cancer risk from 99mTc pyrophosphate imaging for transthyretin cardiac amyloidosis. J Nucl Cardiol. 2018. doi: 10.1007/s12350-018-1307-7.
  • Isoda H, Itagaki Y, Nomura N, et al. Usefulness of dual SPECT with Tc-99m pyrophosphate and Tl-201 to predict further events after acute myocardial infarction with single-vessel coronary artery disease. Clin Nucl Med. 1999;24(4):227-231.
  • Okuda K, Nohara R, Fujita M, et al. Technetium-99m-pyrophosphate uptake as an indicator of myocardial injury without infarct. J Nucl Med 1994;35:1366-1370.
  • Affleck DG, Edelman L, Morris SE, Saffle JR. Assessment of tissue viability in complex extremity injuries: utility of the pyrophosphate nuclear scan. J Trauma. 2001;50:263-269.
  • Chang HR, Kao CH, Lian JD, et al. Evaluation of the severity of traumatic rhabdomyolysis using technetium-99m pyrophosphate scintigraphy. Am J Nephrol. 2001;21:208-214.
Toplam 31 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm Temel Tıp Bilimleri Araştırma Yazıları
Yazarlar

Hatice Aygün

Serdar Savaş Gül 0000-0003-4822-2588

Yayımlanma Tarihi 28 Mart 2019
Kabul Tarihi 25 Mart 2019
Yayımlandığı Sayı Yıl 2019Cilt: 41 Sayı: 1

Kaynak Göster

AMA Aygün H, Gül SS. Protective effect of edaravone on adriamycin-induced cardiotoxicity in rats. CMJ. Mart 2019;41(1):10-18. doi:10.7197/223.vi.531824

Cited By

Evaluation of the protective effect of edaravone on doxorubicin nephrotoxicity by [99mTc]DMSA renal scintigraphy and biochemical methods
Naunyn-Schmiedeberg's Archives of Pharmacology
Fadime Demir
https://doi.org/10.1007/s00210-020-01832-2