Protective effects of melatonin on doxorubicin induced cardiotoxicity in isolated rat heart

Doxorubicin is a highly effective cancer chemotherapeutic agent and its clinical use is limited by its serious cardiotoxicity. Oxidative damage is suggested to play a major role in its cardiotoxicity. In this study we aimed to research the protective effects of melatonin-which is a free radical scavenger and antioxidant -on Doxorubicin-induced cardiotoxicity in isolated perfused rat heart. Male wistar albino rats were divided into four groups: 1.group: control (1ml (i.p) sterile saline), 2.group: Doxorubicin (Dox) (one dose, 10 mg/kg (i.p)), 3.group: Dox (one dose, 10 mg/kg (i.p)) + Melatonin (Mel) for 7 days once a day 10 mg/kg (i.p)), 4.group: Melatonin (for 7 days once a day 10 mg/kg (i.p)). After 7 days, the hearts were isolated and perfused by Langendorff system. Heart rate, coronary perfusion pressure, Left ventricular developed pressure (LVDP), LV (dP/dt)max and LV(dP/dt)min which shows max and min pressures during systole and diastole per time were recorded. As a result; a significant increase in coronary perfusion pressure and LV(dP/dt)min and also a significant decrease in LVDP, LV(dP/dt)max and heart rates in the Dox group according to control group showed altered cardiac functions induced by Dox. versus the Dox group, in the Dox+Mel group the coronary perfusion pressure and LV(dP/dt)min significantly decreased and LVDP and LV(dP/dt)max significantly increased. So it is concluded that melatonin has protective effects on doxorubicin induced cardiotoxicity characterized with altered heart contractility and hemodynamics.

___

1. Octavia Y, Tocchetti CG, Gabrielson KL, et al. Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeutic strategies. J Mol Cell Cardiol 2012; 52: 1213-1225.

2. Tokarska-Schlattner M, Zaugg M, Zuppinger C, et al. New insights into doxorubicin-induced cardiotoxicity: the critical role of cellular energetics. J Mol Cell Cardiol 2006; 41: 389-405.

3. Menna P, Alberto Sordi F. Antrasiklin Degration in Cardiomyocytes: A Journey to Oxidative Survival, Chem. Res. Toxicol 2010; 23: 6-10.

4. Simunek T, Sterba M, Popelova O, et al. Anthracycline induced cardiotoxicity: overview of studies examining the roles of oxidative stress and free cellular iron. Pharmacol Rep 2009; 61: 154-171.

5. Bates SE, Rosing DR, Fojo T, Piekarz RL. Challenges of evaluating the cardiac effects of anticancer agents. Clin Cancer Res 2006; 12: 3871-3874.

6. Li T, Danelisen I, Singal PK. Early changes in myocardial antioxidant enzymes in rats treated with adriamycin. Mol Cell Biochem 2002; 232: 19-26.

7. Suliman HB, Carraway MS, Ali AS, et al. The CO/HO system reverses inhibition of mitochondrial biogenesis and prevents murine doxorubicin cardiomyopathy. J Clin Invest 2007; 117: 3730-3741.

8. Elliott P. Pathogenesis of cardiotoxicity induced by anthracyclines. Semin Oncol 2006; 33: 2-7.

9. Deng S, Kruger A, Kleschyov AL, et al. Gp91phoxcontaining NAD(P)H oxidase increases superoxide formation by doxorubicin and NADPH. Free Radic Biol Med 2007; 42: 466-473.

10. Hrenák J, Arendásová K, Rajkovicová R, et al. Protective effect of captopril, olmesartan, melatonin and compound 21 on doxorubicin- induced nephrotoxicity in rats. Physiol Res 2013; 62: 181-189.

11. Spallarossa P, Garibaldi S, Altieri P, et al. Carvedilol prevents doxorubicin-induced free radical release and apoptosis in cardiomyocytes in vitro. J Mol Cell Cardiol 2004; 37: 837-846.

12. Galano A, Tan DX, Reiter RJ. Melatonin as a natural ally against oxidative stress: a physicochemical examination. J Pineal Res 2011; 51: 1-16.

13. Galano A, Tan DX, Reiter RJ. On the free radical scavenging activities of melatonin's metabolites. AFMK and AMK. J Pineal Res 2013; 54: 245-257.

14. García JJ, López-Pingarrón L, Almeida-Souza P, et al. Protective effects of melatonin in reducing oxidative stress and in preserving the fluidity of biological membranes: a review. J Pineal Res 2014; 56: 225-237.

15. Cuzzocrea S, Reiter RJ. Pharmacological action of melatonin in shock, inflammation and ischemia reperfusion injury. Eur J Pharmacol 2001; 426: 1- 10.

16. Poun P, Bonoron-Adele S, Gouverneur G, Traiosse L. Development of the model of rat isolated perfused heart for the evaluation of anthracycline cardiotoxicity and its circumvention. Br J Pharmacol 1996; 117: 1593- 1599.

17. Tengattini S, Reiter RJ, Tan DX, et al. Cardiovascular diseases: protective effects of melatonin. J Pineal Res 2008; 44: 16-25.

18. Vora J, Khaw BA, Narula J, Boroujerdi M. Protective effect of butylated hydroxyanisole on adriamycin-induced cardiotoxicity. J. Pharm. Pharmacol 1996; 48: 940-944.

19. Tong J, Ganguly PK, Singal PK. Myocardial adrenergic changes at two stages of heart failure due to adriamycin treatment in rats. Am J Physiol 1991; 260: 909-916.

20. De Nigris F, Rienzo M, Schiano C, et al. Prominent cardioprotective effects of third generation beta blocker nebivolol against anthracycline-induced cardiotoxicity using the model of isolated perfused rat heart. Eur J Cancer 2008; 44: 334-340.

21. Nishiyama K, Yasue H, Moriyama Y, et al. Acute effects of melatonin administration on cardiovascular autonomic regulation in healty men. Am Heart J 2001; 141: 149.

22. Morishima I, Okumura K, Matsui H, et al. Zinc accumulation in adriamycin-induced cardiomyopathy in rats: effects of cardioprotective antioxidant. J Pineal Res 1999; 26: 204-210.

23. Reiter RJ, Tan DX. Melatonin: Anovel protective agentgainst oxidative injury of the ischemicreperfused heart. Cardiovascular Research 2003; 58: 10-19.

24. Neilan TG, Blake SL, Ichinose F, et al. Disruption of nitric oxide synthase 3 protects against the cardiac injury, dysfunction, and mortality induced by doxorubicin. Circulation 2007; 116: 506-514.

25. Sahna E, Parlakpinar H, Ozturk F, et al. Melatonin protects against myocardial doxorubicin toxicity in rats: Role of physiological concentrations. J Pineal Res 2003; 35: 257-261.
Eastern Journal of Medicine-Cover
  • ISSN: 1301-0883
  • Başlangıç: 1996
  • Yayıncı: ERBİL KARAMAN
Sayıdaki Diğer Makaleler

Investigation of Brucella seroprevalence in human and livestocks in Igdır, Turkey

Mustafa BERKTAŞ, Fikret ALTINDAĞ, Aydoğan BORA

The determination of health school students' knowledge, attitudes and behaviors on the matter of sexual health in Eastern Turkey

Dilek Kuşaslan AVCI, HÜSEYİN AVNİ ŞAHİN, Gülnihal GÜVENDİ

1Department of Oral Pathology,Manipal College of Dental Sciences, Manipal 2Department of Oral and Maxillofacial Pathology, SDM College of Dental Sciences and Hospital, Dharwad. 3Department of Oral and Maxillofacial Pathology, KLEVK Institute of Dental Sciences, Belagum

Punnya ANGADİ3, Kaveri HALLİKERİ2, Chetana BHAT1

Laparoscopic totally transhiatal diverticulectomy of giant epiphrenic oesophageal diverticulum

Nik Ritza KOSAİ1

Concurrence of prenatally diagnosed Cantrell pentalogy and short and tight umbilical cord: A possible case of hexalogy

Mehmet Güli ÇETİNÇAKMAK, Cihad HAMİDİ, Alpaslan YAVUZ, Cemil GÖYA, Abdussamet BATUR

The determination of health school students' knowledge, attitudes and behaviors on the matter of sexual health in Eastern Turkey

Hüseyin Avni SAHİN, Dilek Kuşaslan AVCİ, Gulnihal GUVENDİ

Protective effects of melatonin on doxorubicin induced cardiotoxicity in isolated rat heart

Zeynep OZGEN ERDOĞMUŞ, MERAL ERDİNÇ, HASAN AKKOÇ, İlker KELLE

Attitude and behaviour of hospital workers on healthy diet and lifestyle in Eastern Turkey

Dilek AVCİ KUŞASLAN, HÜSEYİN AVNİ ŞAHİN, HATİCE TUBA AKBAYRAM

Plasma cobalamin level as a considered tumor marker for hepatocellular Carcinoma

Ersoy ÖKSÜZ1

Spontaneous pseudomeningocele of sphenoid sinus or sphenoid mucocele?: A diagnosis dilemma

Narizan ARİFFİN, Teoh Jian WOEİ, Balwant Singh GENDEH