Assessment of the Effects of Levosimendan and Nigella Sativa on Myocardial Ischemia Reperfusion Injury in Rats

Authors

  • Abdullah Özer
  • Yiğit Kılıç
  • Şaban Cem Sezen
  • Ayşegül Küçük
  • Barış Mardin
  • Metin Alkan
  • Mustafa Arslan Gazi Üniversitesi Tıp Fakültesi
  • Yusuf Ünal
  • Levent Oktar

Abstract

Objective: Ischemia-reperfusion injury is a chain of events put in place by tissue ischemia. Reperfusion following the damage of cell causes an active inflammatory response. In our research we tried to evaluate the protective effect of Levosimendan and Nigella Sativa on myocardial ischemia-reperfusion injury in rats. Methods: We included twenty-four Wistar albino rats in our research. The rats were randomly divided into four experimental groups. The coronary arteries of rats in Group C (control group) were not occluded or reperfused. Left anterior descending coronary artery was ligated for 30 min to perform myocardial IR and then reperfused for 2 h in the IR (IR), IR-Levosimendan (24µg/kg) (IRL) and IR-Nigella Sativa (0.2 mL/kg) (IRNS) group. Results: Inflammation findings were significantly higher in the IR group compared with the C, IR-NS, and IR-L groups (p=0.001, p=0.019, p=0.019, respectively). Compared with the C, IR-NS, and IR-L groups, the microscopic myocardial disorganization was significantly higher among the IR group (p<0.0001, p=0.007, p=0.001, respectively). The light microscopic myocardial tissue interstitial fibrosis levels were significantly higher in the IR group than in the C, IR-NS, and IR-L groups (p<0.0001, p=0.044, p=0.003, respectively). Conclusıon: Levosimendan and NS administration at the beginning of myocardial ischemia can provide varying degrees of protection against negative effects of variations in light microscopic inflammation findings, myocardial disorganization degrees and myocardial tissue interstitial fibrosis levels.

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.

Zimmerman BJ, Granger DN. Reperfusion injury. Surg Clin North Am 1992;72:65–83.

Loft S, Larsen PN, Rasmussen A, Fischer-Nielsen A, Bondesen S, Kirkegaard P, et al. Oxidative DNA damage after transplantation of the liver and small intestine in pigs. Transplantation 1995;59:16–20.

Guo J, Wang SB, Yuan TY, Wu YJ, Yan Y, Li L, e al. Coptisine protects rat heart against myocardial ischemia/reperfusion injury by suppressing myocardial apoptosis and inflammation. Atherosclerosis 2013;231:384-91.

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.

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.

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.

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.

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.

Banerjee S, Kaseb AO, Wang Z, Kong D, Mohammad M, Padhye S, et al. Antitumor activity of gemcitabine and oxaliplatin is augmented by thymoquinone in pancreatic cancer. Cancer Res 2009;69:5575–83.

Chehl N, Chipitsyna G, Gong Q, Yeo CJ, Arafat HA. Anti-inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells. HPB (Oxford) 2009;11:373–81.

El Gazzar MA, El Mezayen R, Nicolls MR, Dreskin SC. Thymoquinone attenuates proinflammatory responses in lipopolysaccharide-activated mast cells by modulating NF-kappaB nuclear transactivation. Biochim Biophys Acta 2007;1770:556–64.

Elsherbiny NM, El-Sherbiny M. Thymoquinone attenuates Doxorubicin-induced nephrotoxicity in rats: role of Nrf2 and NOX4. Chem Biol Interact 2014;223:102–8.

Li F, Rajendran P, Sethi G. Thymoquinone inhibits proliferation, induces apoptosis and chemosensitizes human multiple myeloma cells through suppression of signal transducer and activator of transcription 3 activation pathway. Br J Pharmacol 2010;161:541–54.

Rajput S, Kumar BN, Banik P, Parida S, Mandal M. Thymoquinone restores radiation-induced TGF-beta expression and abrogates EMT in chemoradiotherapy of breast cancer cells. J Cell Physiol 2015;230:620–9.

Samarghandian S, Azimi-Nezhad M, Mehrad-Majd H, Mirhafez SR. Thymoquinone ameliorates acute renal failure in gentamicin-treated adult male rats. Pharmacology. 2015;96:112–7.

Bayrak O, Bavbek N, Karatas OF, Bayrak R, Catal F, Cimentepe E, et al. Nigella sativa protects against ischaemia/reperfusion injury in rat kidneys. Nephrol Dial Transplant. 2008;23:2206–12.

Downloads

Published

19.06.2018

Issue

Section

Original Research

Most read articles by the same author(s)

1 2 3 4 > >>