Effect of Levosimendan and Nigella Sativa on Erythrocyte Deformability During Myocardial Ischaemia-Reperfusion Injury in Rats
Abstract
Objective: Ischaemia-reperfusion (IR) injury is a chain of events put in place by tissue ischaemia. Reperfusion following the cellular damage causes an active inflammatory response. Erythrocyte deformability and plasma viscosity play a critical role in tissue and organ perfusion. In this study we aimed to evaluate the effect of levosimendan and nigella sativa on erythrocyte deformability during myocardial IR injury in rats. Methods: Twenty-four Wistar albino rats were included in the study. The animals were randomly divided into four experimental groups. The coronary arteries of rats in Group C (control group) were not occluded or reperfused. Myocardial IR was performed by ligating the left anterior descending coronary artery for 30 min, followed by 2 h of reperfusion in the IR (IR), IR-levosimendan (24µg/kg) (IRL) group and IR-nigella sativa (0.2 mL/kg) (IRNS) group. Erythrocyte suspensions formed with a PBS buffer solution containing 5% htc were used to measure the deformability. Results: As a result compared to control group, IR increased the relative resistance, a marker of erythrocyte deformability, significantly (p<0.05). There were significant differences between the groups according to the comparisons with ANOVA test (p<0.0001). The results obtained after corrections with Bonferroni test were as follows: Comparisons of the IRL and IRNS groups revealed similar results (p=0.764). The values of the IR group were significantly higher than those of the control, IRNS and IRL groups (p<0.0001, p=0.001, p=0.003, respectively). Conclusion: Rats with IR injury had decreased erythrocyte deformability. This injury might cause more problems in microcirculation. Levosimendan and nigella sativa may be useful in reducing the adverse effects of this type of injury.References
Robertshaw HJ, Hall GM. Diabetes mellitus: anaesthetic management. Anaesthesia 2006;61:1187-90.
McAnulty GR, Robertshaw HJ, Hall GM. Anaesthetic management of patients with diabetes mellitus. Br J Anesth 2000;85:80-90.
Peto K, Nemeth N, Brath E, Takacs IE, Baskurt OK, Meiselman HJ, et al. The effects of renal ischemia-reperfusion on hemorheological factors: preventive role of allopurinol. Clin Hemorheol Microcirc 2007;37:347-58.
Baskurt OK, Meiselman HJ. Blood rheology and hemodynamics. Semin Thromb Hemostas 2003;29:435-50
Brath E, Nemeth N, Kiss F, Sajtos E, Hever T, Matyas L, et al. Changes of local and systemic hemorheological properties in intestinal ischemia-reperfusion injury in the rat model. Microsurgery 2010;30:321-6.
Rognoni A, Lupi A, Lazzero M, Bongo AS, Rognoni G. Levosimendan: from basic science to clinical trials. Recent Pat Cardiovasc Drug Discov 2011;6:9-15.
Toller WG, Stranz C. Levosimendan, a new inotropic and vasodilatory agent. Anesthesiology 2006;104:556-69.
Erdei N, Papp Z, Pollesello P, Edes I, Bagi Z. The levosimendan metabolite OR-1986 elicits vasodilation by activating the K(ATP) and BK(Ca) channels in rat isolated arterioles. Br J Pharmacol 2006;148:696-702.
Kaheinen P, Pollesello P, Levijoki J, Haikala H. Levosimendan increases diastolic coronary flow in isolated guinea pig heart by opening ATP-sensitive potassium channels. J Cardiovasc Pharmacol 2001;37:367-74.
Katircioglu SF, Seren M, Parlar AI, Turan NN, Manavbasi Y, Aydog G, et al. Levosimendan effect on spinal cord ischemia-reperfusion injury following aortic clamping. J Card Surg 2008;23:44-8.
Yasa H, Yakut N, Emrecan B, Ergunes K, Ortac R, Karahan N, et al. Protective effects of levosimendan and iloprost on lung injury induced by limb ischemia-reperfusion: A rabbit model. J Surg Res 2008;147:138-42.
Yakut N, Yasa H, Bahriye Lafci B, Ortac R, Tulukoglu e, Aksun M, et al. The influence of levosimendan and iloprost on renal ischemia-reperfusion: An experimental study. Interact Cardiovasc Thorac Surg 2008;7:235-9.
Gali-Muhtasib H, Roessner A, Schneider-Stock R. Thymoquinone: a promising anti-cancer drug from natural sources. Int J Biochem Cell Biol 2006;38:1249–53.
El-Dakhakhny M. Studies on the chemical constitution of Egyptian N. sativa L. seeds. Planta Med 1963;11:465–70.
Awad AS, Kamel R, Sherief MA. Effect of thymoquinone on hepatorenal dysfunction and alteration of CYP3A1 and spermidine/spermine N-1-acetyl-transferase gene expression induced by renal ischaemia-reperfusion in rats. J Pharm Pharmacol 2011;63:1037–42.
Farag MM, Ahmed GO, Shehata RR, Kazem AH. Thymoquinone improves the kidney and liver changes induced by chronic cyclosporine A treatment and acute renal ischaemia/reperfusion in rats. J Pharm Pharmacol 2015;67:731–9.
Mansour MA, Nagi MN, El-Khatib AS, Al-Bekairi AM. Effects of thymoquinone on antioxidant enzyme activities, lipid peroxidation and DT-diaphorase in different tissues of mice: a possible mechanism of action. Cell Biochem Funct 2002;20:143–51.
Gökce EC, Kahveci R, Gökce A, Cemil B, Aksoy N, Sargon MF, et al. Neuroprotective effects of thymoquinone against spinal cord ischemia-reperfusion injury by attenuation of inflammation, oxidative stress, and apoptosis. J Neurosurg Spine 2016;24:949-59.
Gonca E, Kurt Ç. Cardioprotective effect of Thymoquinone: A constituent of Nigella sativa L., against myocardial ischemia/reperfusion injury and ventricular arrhythmias in anaesthetized rats. Pak J Pharm Sci 2015;28:1267-73.
Hammad FT, Lubbad L. The effect of thymoquinone on the renal functions following ischemia-reperfusion injury in the rat. Int J Physiol Pathophysiol Pharmacol 2016; 25;8:152-9.
Lehtonen L, Põder P. The utility of levosimendan in the treatment of heart failure. Ann Med 2007;39:2-17.
Papp Z, Csapó K, Pollesello P, Haikala H, Edes I. Pharmacological mechanisms contributing to the clinical efficacy of levosimendan. Cardiovasc Drug Rev 2005;23:71-98.
Papp Z, Edes I, Fruhwald S, De Hert SG, Salmenperä M, Leppikangas H, et al. Levosimendan: molecular mechanisms and clinical implications. Consensus of experts on the mechanisms of action of levosimendan. Int J Cardiol 2012;159:82-7.
Katrancioglu N, Karahan O, Kilic AT, Altun A, Katrancioglu O, Polat ZA. The antiangiogenic effects of levosimendan in a CAM assay. Microvasc Res 2012;83:263-6.
Zinchuk VV. Erythrocyte deformability: physiological aspects. Usp Fiziol Nauk 2001;32:66-78.
Kuypers FA. Red cell membrane damage. J Heart Valve Dis 1998;7:387-95.
Pathak A, Lebrin M, Vaccaro A, Senard JM, Despas F. Pharmacology of levosimendan: inotropic, vasodilatory and cardioprotective effects. J Clin Pharm Ther 2013;38:341-9.
Hein M, Zoremba N, Bleilevens C, Bruells C, Rossaint R, Roehl AB. Levosimendan limits reperfusion injury in a rat middle cerebral artery occlusion (MCAO) model. BMC Neurol 2013;13:106.
Yuksel MB, Kavak S, Gecit I, Basel H, Gümrükçüoğlu HA, Demir H, et al. Short-term levosimendan treatment protects rat testes against oxidative stress. Braz J Med Biol Res 2012;45:716-20.
Arslan M, Comu FM, Alkan M, Kiraz HA, Kip G, Özer A, et al. Effect of levosimendan on erythrocyte deformability during myocardial ischaemia-reperfusion injury. Bratisl Med J 2015;116: 47-50.
Hosseinzadeh H, Parvardeh S, Asl MN, Sadeghnia HR, Ziaee T. Effect of thymoquinone and Nigella sativa seeds oil on lipid peroxidation level during global cerebral ischemia-reperffusion injury in rat hippocampus. Phytomedicine 2007; 14: 621-7.
Zaoui A, Cherrah Y, Alaoui K, Mahassine N, Amarouch H, Hassar M. Effects of Nigella sativa fixed oil on blood homeostasis in rat. J Ethnopharmacol 2002;79:23–6.
Al-Jishi SA, Abuo HB. Effect of Nigella sativa on blood hemostatic function in rats. J Ethnopharmacol 2003;85:7–14
