Effect of crocin on nitric oxide synthase expression in post-ischemic isolated rat heart

Document Type: Original Research Article

Authors

1 Physiology Research Center, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

2 Physiology Research Center and Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

3 Department of Virology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

4 Department of Pharmacology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Abstract

Objective: Oxidative stress damages cells and brings about the pathogenesis of ischemia/reperfusion injury. This study was carried out to investigate the preconditioning and cardio protective potential effects of crocin and vitamin E by the eNOS and iNOS express gene in ischemia/reperfusion in rats.
Material & Methods: Male rats were divided into seven groups, namely: sham, control group and experimental groups treated with crocin(10, 20 and 40 mg/kg), vitamin E (100 mg/kg) and combination of crocin (40 mg/kg) with vitamin E (100 mg/kg) that were gavaged The heart was removed and relocated to a Langendorff apparatus and subjected to global ischemia and then the left ventricular end diastolic pressure (LVEDP) were measured as a hemodynamic parameter. Total RNA was extracted from heart frozen tissues. RT-PCR technique was performed by specific primers designed for nitric oxide gene and the results were assessed by agarose gel electrophoresis.
Results: Results after ischemia and reperfusion showed that crocin 40 mg/kg produced a significant improvement of LVEDP as a mechanical function (P<0.05), associated with a reduction of iNOS release (P<0.05). The eNOS mRNA levels were significantly higher in crocin-treated 40 mg/kg compared to controls treated by RT-PCR technique. The combination of crocin and vitamin E have shown more effective on the reduction of iNOS release (P<0.01).
Conclusion: In the isolated rat heart, protective effect of crocin, may possibly be explained by regulating eNOS and iNOS expressions. The Results resultsconfirmed the hypothesis that cardioprotective effect of crocin is partly mediated by nitric oxide. This could explain the cardioprotective action of crocin following ischemia and reperfusion.

Keywords

Main Subjects


Abdullaev FI, Espinosa-Aguirre JJ. 2004. Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials. Cancer Detect Prev, 28: 426-432.

Assimopoulou AN, Sinakos Z, Papageorgiou VP. 2005. Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents. PhytotherRes,19:997-1000.

Atochin DN, Huang PL. 2010. Endothelial nitric oxide synthase transgenic models of endothelial dysfunction. Pflugers Arch, 460: 965-74.

Barouch LA, Harrison RW, Skaf MW, Rosas GO, CappolaTP, Kobeissi ZA, et al. 2002. Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms. Nature, 416: 337-339.

Boyle MP, Weisman HF. 1993. Limitation of infarct expansion and ventricular remodeling by late reperfusion, Study of time and mechanism in a rat model. Circulation, 88: 2872-2883.

Canbaz S, Duran E, Ege T, Sunar H, Cikirikcioglu M, Acipayam M. 2003. The effects of intracoronary administration of vitamin E on myocardial ischemia-reperfusion injury during coronary artery surgery. The Thoracic and cardiovascular surgeon, 51: 57-61.

Chun TY, Bloem LJ, Pratt JH. 2003. Aldosterone inhibits inducible nitric oxide synthase in neonatal rat cardiomyocytes. Endocrinology, 144: 1712-7.

Dianat M, Esmaeilizadeh M, Badavi M, Samarbaf-Zadeh AR, Naghizadeh B. 2014a. Protective Effects of Crocin on Ischemia-reperfusion Induced Oxidative Stress in Comparison With Vitamin E in Isolated Rat Hearts. Jundishapur J Nat Pharm Prod, 9: e17187.

Dhalla NS, Elmoselhi AB, Hata T, Makino N. 2000. Status of myocardial antioxidants in ischemia-reperfusion injury. Cardiovasc Res, 47: 446-456.

Dianat M, Esmaeiliziadeh M, Badavi M, Samarbafzadeh A, Naghizadeh B. 2014b. Cardiac protective effects of crocin on hemodynamic parameters and infarct size in compare vitamin E after ischemia reperfusion in isolated rat heart. Planta Med, 80: 393-398.

Di Napoli P, Chierchia S, Taccardi AA, Grilli A, Felaco M, De Caterina R, et al. 2007. Trimetazidine improves post-ischemic recovery by preserving endothelial nitric oxide synthase expression in isolated working rat hearts. Nitric Oxide, 16: 228-36.

Fernandez J. 2006. Anticancer properties of saffron, Crocus sativus Linn. Adv Phytomed, 2: 313-330.

Garc─▒a-Villalon AL, Monge L, Fernandez N, Salcedo A. 2009. Coronary response to diadenosinepentaphosphate after ischaemia– reperfusion in the isolated rat heart. Cardiovascular Research, 81: 336-343.

Goldspink DF, Burniston JG, Ellison GM, Clark WA, Tan LB. 2004. Catecholamine-induced apoptosis and necrosis in cardiac and skeletal myocytes of the rat in vivo: the same or separate death pathways. ExpPhysiol, 89: 407-416.

Gyurko R, Kuhlencordt P, Fishman MC, Huang PL. 2002. Modulation of mouse cardiac function in vivo by eNOS and ANP. Am J Physiol Heart CircPhysiol, 78: 971-981.

Hosseinzadeh H, Ziaei T. 2006a. Effects of Crocus sativus stigma extract and its constituents, crocin and safranal, on intact memory and scopolamine-induced learning deficits in rats performing the Morris water maze task. J Med Plant, 5: 40-48.

Hosseinzadeh H, Shamsaie F, Mehri S. 2009b. Antioxidant activity of aqueous and ethanolic extracts of Crocus sativus L. stigma and its bioactive constituent, crocin and safranal. Pharmacogn Mag, 5: 419-424.

Jahanbakhsh Z, Rasoulian B, Jafari M, Shekarforoush S, Esmailidehaj M, Mohammadi MT. et al. 2012. Protective effect of crocin against reperfusion-induced cardiac arrhythmiasin anaesthetized rats. EXCLI J, 11: 20-9.

Kuhlencordt PJ, Gyurko R, Han F, Scherrer-Crosbie M, Aretz TH, et al. 2001. Accelerated atherosclerosis, aortic aneurysm formation, and ischemic heart disease in apolipoprotein E/endothelial nitric oxide synthase double knockout mice. Circulation, 104: 448-454.

Lopaschuk GD, Barr R, Thomas PD, Dyck JR. 2003. Beneficial effects of Trimetazidine in ex vivo working ischemic hearts are due to a stimulation of glucose oxidation secondary to inhibition of   long-chain 3-ketoacyl coenzyme A thiolase, Circ Res, 93: 33-37. 

Ochiai T, Shimeno H, Mishima K, Iwasaki K, Fujiwara M, Tanaka H, et al. 2007. Protective effects of carotenoids from saffron on neuronal injury in vitro and in vivo. Biochimica et biophysicaacta, 1770: 578-84.

Osada M, Netticadan T, Tamura K, Dhalla NS. 1998. Modification of ischemia–reperfusion induced changes in cardiac sarcoplasmic reticulum by preconditioning. Am J Physiol, 274: 2025- 2034.

Shaul PW.  2002. Regulation of endothelial nitric oxide synthase location. Annu Rev Physiol, 64: 749-774.

  Srivastava S, Chandrasekar B, Gu Y, Luo J, Hamid T, Hill BG. 2007. Down regulation of CuZn-superoxide dismutase contributes to beta-adrenergic receptor-mediated oxidative stress in the heart. Cardiovasc Res. 74: 445-455.

Scherrer-Crosbie M, Ullrich R, Bloch KD, Nakajima H, Nasseri B, Aretz HT et al. 2001. Endothelial nitric oxide synthase limits left ventricular remodeling after myocardial infarction in mice. Circulation, 104: 1286-1291.

Upaganlawar A and Balaraman R. 2010. Effect of vitamin E and green tea on hemodynamic, electro cardiographic and some biochemical alterations in experimentally induced myocardial infarction in rats. European Journal of Integrative Medicine, 2: 135-141.  

Zhou B, Wu LM, Yang L, Liu ZL. 2005. Evidence for alpha-tocopherol regeneration reaction of green tea polyphenols in SDS micelles. Free radical biology & medicine, 38: 78-84.