Buket DEMİRCİ, Saliha AKSUN, Ufuk ERYILMAZ

Pycnogenol®’ün Sıçanlarda, Sisplatin ile İndüklenen Kardiyotoksisite Üzerine Koruyucu Etkisi

Amaç: Bu çalışmada sıçan kalbi üzerinde sisplatin (CIS) kardiyotoksisitesi, sıçan miyokardı oksidatif hasarını, troponin I ve serum S100A1 düzeyleri kullanılarak araştırılmıştır. Önceki çalışmalar, Pycnogenol®’un (PYC) hücre koruyucu etkisinin antioksidan ve anti-enflamatuvar özelliklerine bağlı olduğunu bildirmiştir. Bu nedenle, bu çalışmada PYC’nin miyokardiyal koruyucu etkisi araştırılmıştır. Gereç ve Yöntemler: Sıçanlar randomize olarak grup başına 5 olacak şekilde dört gruba ayrıldı. Kontrol grupları, PYC grubu: 10 mg/kg 7 gün boyunca intraperitoneal PYC, 5 gün intraperitoneal olarak sisplatinin 15 mg/kg tek doz enjeksiyonu, sisplatin + PYC grubu: 10 mg/kg PYC intraperitoneal olarak 7 gün boyunca, artı beşinci günde 15 mg/kg tek sisplatin enjeksiyonu. Kalp ve serum örnekleri 8. günde elde edildi. Bulgular: CIS ve PYC eş-tedavi grubunda katalaz seviyesi artmış (43,61±15,16'dan 60,80±21,36’ya, p

Protective Effect of Pycnogenol® on Cisplatin Induced-Cardiotoxicity in Rats

Objective: This study investigated the cardiotoxicity of cisplatin (CIS) on rat heart by using the oxidative damage of the rat myocardium, troponin I and serum S100A1 levels. Previous studies have reported that cell-protective effect of Pycnogenol® (PYC) depended on its antioxidant and anti-inflammatory properties. Hence, the myocardial protective effect of PYC was investigated in this study. Materials and Methods: Rats were randomly grouped to four with 5 rats in each group. The groups were consisted of control group, PYC group: 10 mg/kg PYC for 7 days, CIS group: 15 mg/kg single injection of CIS on the 5th day, CIS + PYC group: 10 mg/kg PYC for 7 days, plus 15 mg/kg single injection of CIS on the 5th day. Heart and serum samples were acquired subsequently. Results: CIS and PYC co-treatment group had increased catalase level (from 43.61±15.16 to 60.80±21.36, p

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Prestayko AW, D'Aoust JC, Issell BF, Crooke ST. Cisplatin (cisdiamminedichloroplatinum II). Cancer Treat Rev1979; 6: 17-39.
Loehrer PJ, Einhorn LH. Drugs five years later. Cisplatin. Ann Intern Med 1984; 100: 704-13.
Varga ZV, Ferdinandy P, Liaudet L, Pacher P. Drug-induced mitochondrial dysfunction and cardiotoxicity. Am J Physiol Heart Circ Physiol 2015; 309: 1453-67.
Luzzi R, Belcaro G, Hu S, Dugall M, Hosoi M, Cacchio M, et al. Improvement in symptoms and cochlear flow with pycnogenol in patients with Meniere's disease and tinnitus. Minerva Med 2014; 105: 245-54.
Parveen K, Khan MR, Siddiqui WA. Pycnogenol prevents potassium dichromate K2Cr2O7-induced oxidative damage and nephrotoxicity in rats. Chem Biol Interact 2009; 181: 343-50.
Yang YS, Ahn TH, Lee JC, Moon CJ, Kim SH, Jun W, et al. Protective effects of Pycnogenol on carbon tetrachloride-induced hepatotoxicity in Sprague-Dawley rats. Food Chem Toxicol 2008; 46: 380-7.
Mojzisova G, Mirossay L, Kucerova D, Kyselovic J, Mirossay A, Mojzis J. Protective effect of selected flavonoids on in vitro daunorubicininduced cardiotoxicity. Phytother Res 2006; 20: 110-4.
Donato R. Functional roles of S100 proteins, calcium-binding proteins of the EF-hand type. Biochim Biophys Acta 1999; 1450: 191-231.
Vincent DT, Ibrahim YF, Espey MG, Suzuki YJ. The role of antioxidants in the era of cardio-oncology. Cancer Chemother Pharmacol 2013; 72: 1157-68.
Dirican A, Sahin O, Tasli F, Sogut E, Kucukzeybek Y, Alacacioglu A, et al. Thymoquinone enhances cisplatin-induced nephrotoxicity in high dose. J Onc Sci 2016; 1: 17-24.
Aebi H. Catalase. In: Bergemeyer HU, editor. Methods of Enzymatic Analysis. New York - London: Academic Press; 1974.p. 673-84.
El-Awady el SE, Moustafa YM, Abo-Elmatty DM, Radwan A. Cisplatin-induced cardiotoxicity: Mechanisms and cardioprotective strategies. Eur J Pharmacol 2011; 650: 335-41.
Enseleit F, Sudano I, Periat D, Winnik S, Wolfrum M, Flammer AJ, et al. Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study. Eur Heart J 2012; 33: 158997.
Feng WH, Wei HL, Liu GT. Effect of PYCNOGENOL on the toxicity of heart, bone marrow and immune organs as induced by antitumor drugs. Phytomedicine 2002; 9: 414-8.
Ma H, Jones KR, Guo R, Xu P, Shen Y, Ren J. Cisplatin compromises myocardial contractile function and mitochondrial ultrastructure: role of endoplasmic reticulum stress. Clin Exp Pharmacol Physiol 2010; 37: 460-5.
Zsengeller ZK, Ellezian L, Brown D, Horvath B, Mukhopadhyay P, Kalyanaraman B, et al. Cisplatin nephrotoxicity involves mitochondrial injury with impaired tubular mitochondrial enzyme activity. J Histochem Cytochem 2012; 60: 521-9.
Mukhopadhyay P, Horvath B, Zsengeller Z, Batkai S, Cao Z, Kechrid M, et al. Mitochondrial reactive oxygen species generation triggers inflammatory response and tissue injury associated with hepatic ischemia-reperfusion: therapeutic potential of mitochondrially targeted antioxidants. Free Radic Biol Med 2012; 53: 1123-38.
Donato R, Cannon BR, Sorci G, Riuzzi F, Hsu K, Weber DJ, et al. Functions of S100 proteins. Curr Mol Med 2013; 13: 24-57.
Faa A, Senes G, Locci A, Pampaloni P, Pais ME, Piras B, et al. S100B protein expression in the heart of deceased individuals by overdose: a new forensic marker? Clinics (Sao Paulo) 2012; 67: 821-6.
Most P, Seifert H, Gao E, Funakoshi H, Völkers M, Heierhorst J, et al. Cardiac S100A1 protein levels determine contractile performance and propensity toward heart failure after myocardial infarction. Circulation 2006; 114: 1258-68.
Duarte-Costa S, Castro-Ferreira R, Neves JS, Leite-Moreira AF. S100A1: a major player in cardiovascular performance. Physiol Res 2014; 63: 669-81.
Eryilmaz U, Demirci B, Aksun S, Boyacioglu M, Akgullu C, Ilgenli TF, et al. S100A1 as a Potential Diagnostic Biomarker for Assessing Cardiotoxicity and Implications for the Chemotherapy of Certain Cancers. PLoS One 2015; 10: e0145418.