Ratlarda Levosimendan ve Nigella Sativa'nın Miyokardiyal İskemi Reperfüzyon Hasarına Etkilerinin Değerlendirilmesi
Giriş: İskemi-reperfüzyon hasarı, doku iskemisi tarafınca meydana gelen bir olaylar zinciridir. Hücre hasarını takiben reperfüzyon, aktif bir inflamatuar yanıta neden olur. Araştırmamızda, ratlarda Levosimendan ve Nigella Sativa'nın miyokardiyal iskemi-reperfüzyon hasarı üzerindeki koruyucu etkisini değerlendirmeyi amaçladık. Yöntem: Araştırmamıza yirmi dört adet Wistar albino rat dahil ettik. Ratlar rastgele dört deney grubuna ayrıldı. Grup K'daki (kontrol grubu) ratların koroner arterleri oklude veya reperfüze edilmedi. Sol ön inen koroner arter miyokardiyal İR yapmak için 30 dakika bağlandı ve daha sonra İR (İR), İRLevosimendan (24ug / kg) (İRL) ve İR-Nigella Sativa (0.2 mL / kg) (İRNS) gruplarında 2 saat reperfüze edildi . Bulgular: İnflamasyon bulguları İR grubunda C, İR-NS ve İR-L gruplarına göre anlamlı olarak yüksek bulundu (p=0.001, p=0.019, p=0.019, sırasıyla). K, İR-NS ve İR-L grupları ile karşılaştırıldığında, mikroskobik miyokardiyal disorganizasyon, İR grubunda anlamlı olarak daha yüksekti (p
Assessment of the Effects of Levosimendan and Nigella Sativa on Myocardial Ischemia Reperfusion Injury in Rats
Objective: Ischemia-reperfusion injury is a chain of events put in place bytissue ischemia. Reperfusion following the damage of cell causes an activeinflammatory response. In our research we tried to evaluate the protectiveeffect of Levosimendan and Nigella Sativa on myocardial ischemia-reperfusioninjury in rats.Methods: We included twenty-four Wistar albino rats in our research. The ratswere randomly divided into four experimental groups. The coronary arteriesof rats in Group C (control group) were not occluded or reperfused. Leftanterior descending coronary artery was ligated for 30 min to performmyocardial 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 groupcompared 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 microscopicmyocardial disorganization was significantly higher among the IR group(p
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- 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-acetyltransferase
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 DTdiaphorase
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 ischemiareperfusion
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 Doxorubicininduced
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.