Yıl: 2016 Cilt: 46 Sayı: 1 Sayfa Aralığı: 166 - 173 Metin Dili: İngilizce

Effects and mechanisms of curcumin on the hemodynamic variables of isolated perfused rat hearts

Öz:
Background/aim: There is no information on the dose response relationship of curcumin on the hemodynamic variables of the heart at the organ level in isolated perfused rat hearts. We aimed to investigate the effects and mechanisms of curcumin on the hemodynamic variables of isolated perfused rat hearts. Materials and methods: Rats were randomly divided into 9 groups. The isolated rat heart was retrogradely perfused with modified Krebs Henseleit solution. After the stabilization period, each group was administered one of the following treatments for 25 min: saline, dimethyl sulfoxide, and curcumin (0.2 µM, 1 µM, and 5 µM); atropine (1 µM); atropine (1 µM) + curcumin (1 µM); L-NAME (100 µM); or L-NAME (100 µM) + curcumin (1 µM). Hemodynamic variables of the heart were measured. Results: Curcumin at dose of 1 µM decreased the heart rate (from 271 ± 11.1 to 200.4 ± 14.3 beats/min, P = 0.011) but increased enddiastolic pressure (from 7.0 ± 0.4 to 54.6 ± 7.9 mmHg, P = 0.0008). A dose of 5 µM curcumin caused a decrease in the developed pressure (from 87.58 ± 9.0 to 65.40 ± 7.0 mmHg, P = 0.047) but an increase in the end-diastolic pressure (from 6.8 ± 0.6 to 48.9 ± 7.7 mmHg, P = 0.005). Atropine (1 µM) reversed the effects of curcumin on the heart. Conclusion: Our results suggest that curcumin produces dose-dependent negative chronotropic and inotropic effects in isolated perfused rat hearts.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Maheshwari RK, Singh AK, Gaddipati J, Srimal RC. Multiple biological activities of curcumin: a short review. Life Sci 2006; 78: 2081–2087.
  • 2. Srivastava G, Mehta JL. Currying the heart: curcumin and cardioprotection. J Cardiovasc Pharmacol Ther 2009; 1: 22–27.
  • 3. Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “curecumin”: from kitchen to clinic. Biochem Pharmacol 2008; 75: 787–809.
  • 4. Swamy AV, Gulliaya S, Thippeswamy A, Koti BC, Manjula DV. Cardioprotective effect of curcumin against doxorubicininduced myocardial toxicity in albino rats. Indian J Pharmacol 2012; 1: 73–77.
  • 5. Manikandan P, Sumitra M, Aishwarya S, Manohar BM, Lokanadam B, Puvanakrishnan R. Curcumin modulates free radical quenching in myocardial ischaemia in rats. Int J Biochem Cell Biol 2004; 36: 1967–1980. 6. Srivastava R,  Dikshit M,  Srimal RC,  Dhawan BN. Antithrombotic effect of curcumin. Thromb Res 1985; 40: 413–417.
  • 7. Li HL,  Liu C,  De Couto G,  Ouzounian M,  Sun M,  Wang AB, Huang Y, He CW, Shi Y, Chen X et al. Curcumin prevents and reverses murine cardiac hypertrophy. J Clin Invest 2008; 118: 879–893.
  • 8. Nirmala C, Puvanakrishnan R. Effect of curcumin on certain lysosomal hydrolases in isoproterenol-induced myocardial infarction in rats. Biochem Pharmacol 1996; 51: 47–51.
  • 9. Venkatesan N. Curcumin attenuation of acute adriamycin myocardial toxicity in rats. Br J Pharmacol 1998; 124: 425–427.
  • 10. Schoonderwoerd BA, Smit MD, Pen L, Van Gelder IC. New risk factors for atrial fibrillation: causes of not-so-lone atrial fibrillation. Europace 2008; 10: 668–673.
  • 11. Quiles JL,  Mesa MD,  Ramírez-Tortosa CL,  Aguilera CM, Battino M, Gil A. Curcuma longa extract supplementation reduces oxidative stress and attenuates aortic fatty streak development in rabbits. Arterioscler Thromb Vasc Biol 2002; 22: 1225–1231.
  • 12. Bronte E, Coppola G, Di Miceli R, Sucato V, Russo A, Novo S. Role of curcumin in idiopathic pulmonary arterial hypertension treatment: a new therapeutic possibility. Med Hypotheses 2013; 81: 923–926. 
  • 13. Sharma RA,  Euden SA,  Platton SL,  Cooke DN,  Shafayat A,  Hewitt HR,  Marczylo TH,  Morgan B,  Hemingway D, Plummer SM et al. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res 2004; 10: 6847–6854.
  • 14. Kaygısız Z, Kaygısız B, Kılınç E. The effect of Des-Arg9- bradykinin and bradykinin-potentiating peptide C on isolated rat hearts. Acta Physiol Hung 2013; 100: 280–288.
  • 15. Deng XF, Mulay S, Chemtob S, Varma DR. Mechanisms of the atrium-specific positive inotropic activities of quinidine- and atropine-like agents in rats. J Pharmacol Exp Ther 1997; 281: 322–329.
  • 16. Legssyer A,  Ziyyat A,  Mekhfi H,  Bnouham M,  Tahri A, Serhrouchni M, Hoerter J, Fischmeister R. Cardiovascular effects of Urtica dioica L. in isolated rat heart and aorta. Phytother Res 2002; 16: 503–507.
  • 17. Pabla R, Curtis MJ. Effect of endogenous nitric oxide on cardiac systolic and diastolic function during ischemia and reperfusion in the rat isolated perfused heart. J Mol Cell Cardiol 1996; 28: 2111–2121.
  • 18. Ansari MN, Bhandari U, Pillai KK. Protective role of curcumin in myocardial oxidative damage induced by isoproterenol in rats. Hum Exp Toxicol 2007; 26: 933–938.
  • 19. Srinivasan K. Antioxidant potential of spices and their active constituents. Crit Rev Food Sci Nutr 2014; 54: 352–372.
  • 20. Chowdhury R, Nimmanapalli R, Graham T, Reddy G. Curcumin attenuation of lipopolysaccharide induced cardiac hypertrophy in rodents. ISRN Inflamm 2013; 1–8.
  • 21. White WB. Heart rate and the rate-pressure product as determinants of cardiovascular risk in patients with hypertension. Am J Hypertens 1999; 12: 50–55.
  • 22. Buccino RA, Sonnenblick EH, Cooper T, Braunwald E. Direct positive inotropic effect of acetylcholine on myocardium. Evidence for multiple cholinergic receptors in the heart. Circ Res 1966; 19: 1097–1088.
  • 23. Cheng TC, Lu CC, Chung HH, Hsu CC, Kakizawa N, Yamada S, Cheng JT. Activation of muscarinic M-1 cholinoceptors by curcumin to increase contractility in urinary bladder isolated from Wistar rats. Neurosci Lett 2010; 473: 107–109.
  • 24. Doi Y, Masuyama T, Yamamoto K, Mano T, Naito J, Nagano R, Kondo H, Hori M. Coronary back flow pressure is elevated in association with increased left ventricular end-diastolic pressure in humans. Angiology 1996; 47: 1047–1051.
  • 25. Zhang C,  Zha DG,  Du RS,  Hu F,  Li SH,  Wu XY,  Liu YL. Evaluation of left ventricular diastolic function in canine acute myocardial ischemia using velocity vector imaging and quantitative tissue velocity imaging. Nan Fang Yi Ke Da Xue Xue Bao 2009; 29: 1333–1336.
  • 26. Adaramoye OA,  Anjos RM,  Almeida MM,  Veras RC,  Silvia DF,  Oliveira FA,  Cavalcante KV,  Araújo IG,  Oliveira AP, Medeiros IA. Hypotensive and endothelium independent vasorelaxant effects of methanolic extract from Curcuma longa L. in rats. J Ethnopharmacol 2009; 124: 457–462.
  • 27. Sato M, Cordis GA, Maulik N, Das DK. SAPKs regulation of ischemic preconditioning. Am J Physiol Heart Circ Physiol 2000; 279: 901–907.
  • 28. Conti V, Russomanno G, Corbi G, Izzo V, Vecchione C, Filippelli A. Adrenoreceptors and nitric oxide in the cardiovascular system. Front Physiol 2013; 4: 1–11.
  • 29. Loscalzo J, Welch G. Nitric oxide and its role in the cardiovascular system. Prog Cardiovasc Dis 1995; 38: 87–104.
  • 30. Brouet I, Ohshima H. Curcumin, an anti-tumour promoter and anti-inflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages. Biochem Biophys Res Commun 1995; 206: 533–540.
  • 31. Brini M, Carafoli E. Calcium pumps in health and disease. Physiol Rev 2009; 89: 1341–1378.
  • 32. Bilmen JG, Khan SZ, Javed MH, Michelangeli F. Inhibition of the SERCA Ca2+ pumps by curcumin. Curcumin putatively stabilizes the interaction between the nucleotide-binding and phosphorylation domains in the absence of ATP. Eur J Biochem 2001; 268: 6318–6327.
  • 33. Logan-Smith MJ, Lockyer PJ, East JM, Lee AG. Curcumin, a molecule that inhibits the Ca2+-ATPase of sarcoplasmic reticulum but increases the rate of accumulation of Ca2+. J Biol Chem 2001; 276: 46905–46911.
  • 34. Sumbilla C, Lewis D, Hammerschmidt T, Inesi G. The slippage of the Ca2+ pump and its control by anions and curcumin in skeletal and cardiac sarcoplasmic reticulum. J Biol Chem 2002; 277: 1390–1396.
  • 35. Lee SW, Nah SS, Byon JS, Ko HJ, Park SH, Lee SJ, Shin WY, Jin DK. Transient complete atrioventricular block associated with curcumin intake. Int J Cardiol 2011; 150: 50–52.
APA KILINÇ E, KAYGISIZ Z, BENEK B, GÜMÜŞTEKİN K (2016). Effects and mechanisms of curcumin on the hemodynamic variables of isolated perfused rat hearts. Turkish Journal of Medical Sciences, 46(1), 166 - 173.
Chicago KILINÇ ERKAN,KAYGISIZ Ziya,BENEK Bedri Selim,GÜMÜŞTEKİN Kenan Effects and mechanisms of curcumin on the hemodynamic variables of isolated perfused rat hearts. Turkish Journal of Medical Sciences 46, no.1 (2016): 166 - 173.
MLA KILINÇ ERKAN,KAYGISIZ Ziya,BENEK Bedri Selim,GÜMÜŞTEKİN Kenan Effects and mechanisms of curcumin on the hemodynamic variables of isolated perfused rat hearts. Turkish Journal of Medical Sciences, vol.46, no.1, 2016, ss.166 - 173.
AMA KILINÇ E,KAYGISIZ Z,BENEK B,GÜMÜŞTEKİN K Effects and mechanisms of curcumin on the hemodynamic variables of isolated perfused rat hearts. Turkish Journal of Medical Sciences. 2016; 46(1): 166 - 173.
Vancouver KILINÇ E,KAYGISIZ Z,BENEK B,GÜMÜŞTEKİN K Effects and mechanisms of curcumin on the hemodynamic variables of isolated perfused rat hearts. Turkish Journal of Medical Sciences. 2016; 46(1): 166 - 173.
IEEE KILINÇ E,KAYGISIZ Z,BENEK B,GÜMÜŞTEKİN K "Effects and mechanisms of curcumin on the hemodynamic variables of isolated perfused rat hearts." Turkish Journal of Medical Sciences, 46, ss.166 - 173, 2016.
ISNAD KILINÇ, ERKAN vd. "Effects and mechanisms of curcumin on the hemodynamic variables of isolated perfused rat hearts". Turkish Journal of Medical Sciences 46/1 (2016), 166-173.