Hüseyin BİLGE, İbrahim YILDIZHAN, Burak Veli ÜLGER, Ulaş ADAY, Ömer BAŞOL, Kadriye ÇİÇEKÇİ, Eda YİLDİZHAN

KARACİĞER İSKEMİ VE REPERFÜZYON HASARINDA KALP DOKUSUNDA MEYDANA GELEN HASARIN ÖNLENMESİNDE TAKSİFOLİN’İN KORUYUCU ETKİNLİĞİ: DENEYSEL ÇALIŞMA

Amaç: Karaciğer iskemi ve reperfüzyon (I/R) klinik uygulamalarında geri dönüşümsüz ciddi bir sağlık sorunudur. Taksifolin (Tax) deniz çamı kabuğunda, Douglas köknar kabuğunda ve Sibirya karaçam ağacında, bulunan elde edilmesi ve kullanılması kolay bir ajandır. Bizde yaptığımız bu çalışmanın sonucunda karaciğer I/R hasarında gelişebilecek kalp dokusu hasarının düzeltilmesinde Taksifolin’in koruyucu etkinliğini incelemeye karar verdik. Yöntemler: Çalışmamızda ortalama 8-10 haftalık, 250-300 gram ağırlıklarında toplam 28 adet Wistar Albino cinsi ratlar kullanıldı. Grup 1 (n=7): kontrol grubu, Grup 2 (n=7): Tax grubu olup 50 mg/kg doz ile oral yoldan 3 hafta süreyle, Grup 3 (n=7): Karaciğer I/R grubunda ise 30 dakika iskemi ve 120 dakika reperfüzyon uygulandı. Grup 4 (n=7): Tax+Karaciğer I/R grubu idi. Bulgular: Çalışmamızda oksidatif stresi değerlendirmek için MDA analizi yapıldı. MDA değerlerinin istatistiksel analizinde; Tax grubu ile Tax+Karaciğer I/R grubunun serum MDA değerleri arasında istatistiksel olarak anlamlı fark olduğu, Tax grubunun MDA düzeyinin daha düşük olduğu görüldü (p<0.05). Myosit hasarı skorlamasında; en yüksek hasar skorlamasının karaciğer I/R grubunda olduğu izlenirken, Tax+Karaciğer I/R grubunun hasar skorlamasının I/R grubundan anlamlı olarak daha düşük olduğu izlendi (p<0.05). Sonuç: Çalışmamızın sonucunda karaciğer I/R sonucu serum MDA düzeylerinde artış olduğu ve kalp dokusunda histopatolojik değişikliklerin meydana geldiği görülmüştür. Fakat bu durumun düzeltilmesinde Taksifolin başarılı şekilde etkinlik göstermiştir

Anahtar Kelimeler:

Taksifolin, Oksidatif Stres, Karaciğer iskemi ve reperfüzyon, Kalp

Protective Effect of Taxifolin in The Prevention of Cardiac Tissue Damage in Liver Ischemia and Reperfusion Injury: Experimental Study

Aim: Liver ischemia and reperfusion (I/R) is a serious, irreversible health problem in clinical practice. Taxifolin (Tax) is an easy to obtain and use agent found in maritime pine bark, Douglas fir bark and Siberian larch wood. In this study, we examined the protective efficacy of Taxifolin in the correction of cardiac tissue damage that may develop in liver I/R damage. Methods: In our study, a total of 28 Wistar Albino rats, 8-10 weeks old, weighing 250-300 grams, were used. Group 1 (n=7): control group, Group 2 (n=7): Tax group with 50 mg/kg dose orally for 3 weeks, Group 3 (n=7): Liver I/R group for 30 minutes ischemia and 120 minutes of reperfusion were performed. Group 4 (n=7): Tax+Liver I/R group. Results: In our study, MDA analysis was performed to evaluate oxidative stress. In the statistical analysis of MDA values, we observed that there was a statistically significant difference between the serum MDA values of the Tax group and the Tax+Liver I/R group, and the MDA level of the Tax group was lower (p<0.05). In myocyte damage scoring, we observed that the liver I/R group had the highest damage score, while the damage score of the Tax+Liver I/R group was significantly lower than the I/R group (p<0.05). Conclusion: As a result of our study, we observed that there was an increase in serum MDA levels as a result of liver I/R and histopathological changes occurred in the heart tissue. However, Taxifolin has been successful in ameliorating this situation.

Keywords:

Taxifolin, Oxidative Stress, Liver ischemia and reperfusion, Heart,

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1.Peralta C, Jiménez-Castro M.B, Gracia-Sancho J. Hepatic ischemia and reperfusion injury: Effects on the liver sinusoidal milieu. J. Hepatol. 2013;59(5):1094–106. https://doi.org/10.1016/j.jhep.2013.06.017
2.Fu P, Li W. Role of nitric oxide in hepatic ischemia-reperfusion injury. World J Gastroenterol. 2010; 16(48): 6079–86. https://doi.org/10.3748/wjg.v16.i48.6079
3.Jaeschke H. Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning. Am. J. Physiol. Gastrointest Liver Physiol. 2003; 284(1): G15-26. https://doi.org/10.1152/ajpgi.00342.2002
4.Montalvo-Jave EE, Escalante-Tattersfield T, Ortega-Salgado JA, et al. Factors in the pathophysiology of the liver ischemia-reperfusion injury. J. Surg. Res. 2008; 147(1): 153-9. https://doi.org/10.1016/j.jss.2007.06.015
5.Carden DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J. Pathology. 2000; 190(3): 255-66. https://doi.org/10.1002/(SICI)1096-9896(200002)190:3<255::AID-PATH526>3.0.CO;2-6.
6.Peralta C, Fern´Andez L, Pan´es J, et al. Preconditioning protects against systemic disorders associated with hepatic ischemia-reperfusion through blockade of Tumor necrosis factor–induced P-selectin up-regulation in the rat. Hepatology. 2001; 33(1): 100-13. https://doi.org/10.1053/jhep.2001.20529
7.Gracia-Sancho J, Villarreal Jr G, Zhang Y, et al. Flow cessation triggers endothelial dysfunction during organ cold storage conditions: Strategies for pharmacologic intervention. Transplantation. 2010; 90(2): 142-9. https://doi.org/10.1097/TP.0b013e3181e228db
8.Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. Scientific World Journal. 2013; 2013: 162750. https://doi.org/10.1155/2013/162750
9.Mülek M, Seefried L, Genest F, et al. Distribution of constituents and metabolites of maritime pine bark extract (Pycnogenol®) into serum, blood cells, and synovial fluid of patients with severe osteoarthritis: a randomized controlled trial. Nutrients. 2017; 9(5): 443. https://doi.org/10.3390/nu9050443
10.Slimestad R, Fossen T, Vågen IM. Onions: a source of unique dietary flavonoids. J Agric Food Chem. 2007;1 2(55): 10067– 80. https://doi.org/10.1021/jf0712503
11.Ali F, Abo-Youssef A, Messiha B, et al. Protective effects of quercetin and ursodeoxycholic acid on hepatic ischemia-reperfusion injury in rats. Clin Pharmacol Biopharm. 2014; 4: 1. https://doi.org/10.4172/2167-065X.1000128
12.Chaves JC, Neto FS, Ikejiri AT, et al. Period of hyperbaric oxygen delivery leads to different degrees of hepatic ishemia/reperfusion injury in rats. In: Transplantation proceedings, Elsevier. 2016; 48(2): 516-20. https://doi.org/10.1016/j.transproceed.2015.11.035
13.Kamel EO, Hassanein EHM, Ahmed MA, et al. Perindopril Ameliorates Hepatic Ischemia Reperfusion Injury Via Regulation of NF-κB-p65/TLR-4, JAK1/STAT-3, Nrf-2, and PI3K/Akt/mTOR Signaling Pathways. Anat Rec (Hoboken). 2020; 303(7): 1935-49. https://doi.org/10.1002/ar.24292
14.Bedir F, Kocatürk H, Yapanoğlu T, et al. Protective effect of taxifolin against prooxidant and proinflammatory kidney damage associated with acrylamide in rats. Biomedicine&Pharmacotherapy. 2021; 139: 111660. https://doi.org/10.1016/j.biopha.2021.111660
15.Tunik S, Aluclu MU, Acar A, et al. The effects of intravenous immunoglobulin on cerebral ischemia in rats: An experimental study. Toxicol Ind Health. 2016; 32(2): 229-34. https://doi.org/10.1177/0748233713498461
16.Satoh K. Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method. Clin Chim Acta. 1978; 90(1): 37-43. https://doi.org/10.1016/0009-8981(78)90081-5
17.Tokatli F, Uzal C, Doganay L, et al. The potential cardioprotective effects of amifostine in irradiated rats. Int J Radiat Oncol Biol Phys 2004; 58(4): 1228-34. https://doi.org/10.1016/j.ijrobp.2003.09.071
18.Glantzounis GK, Salacinski HJ, Yang W, Davidson BR, Seifalian AM. The contemporary role of antioxidant therapy in attenuating liver ischemia-reperfusion injury: A review. Liver Transplantation 2005; 11(9): 1031-47.
19.Günel E, Cağlayan F, Cağlayan O, et al. Treatment of intestinal reperfusion injury using antioxidative agents. J Pediatr Surg. 1998; 33(10): 1536-9. https://doi.org/10.1016/s0022-3468(98)90492-4
20.Sawyer DB, Colucci WS. Mitochondrial oxidative stress in heart failure : “oxygen wastage” revisited. Circ Res. 2000; 86(2): 119-20. https://doi.org/10.1161/01.res.86.2.119
21.Perrelli M, Pagliaro P, Penna C. Ischemia/reperfusion injury and cardioprotective mechanisms: role of mitochondria and reactive oxygen species. World J Cardiol. 2011; 3(6):186-200. https://doi.org/10.4330/wjc.v3.i6.186
22.Seker U, Nergiz Y, Aktas A, et al. Trolox is more successful than allopurinol to reduce degenerative effects of testicular ischemia/reperfusion injury in rats. Journal of Pediatric Urology. 2020; 16(4): 465.e1-465.e8. https://doi.org/10.1016/j.jpurol.2020.05.008
23.Ozevren H, Irtegün S, Deveci E, et al. Ganoderma Lucidum Protects Rat Brain Tissue Against Trauma-Induced Oxidative Stress. Korean J Neurotrauma. Korean J Neurotrauma. 2017; 13(2): 76-84. https://doi.org/10.13004/kjnt.2017.13.2.76
24.Wang Q, Wang L, Gaiping L, et al. A simple and sensitive method for determination of taxifolin on palladium nanoparticles supported poly (diallyldimethylammonium chloride) functionalized graphene modified electrode. Talanta. 2017; 164: 323-9. https://doi.org/10.1016/j.talanta.2016.11.045
25.Topal F, Nar M, Gocer H, et al. Antioxidant activity of taxifolin: An activity–structure relationship. J Enzyme Inhib Med Chem. 2016; 31(4): 674-83. https://doi.org/10.3109/14756366.2015.1057723
26.Maksimovich NY, Dremza IK, Troian EI, et al. The correcting effects of dihydroquercetin in cerebral ischemia-reperfusion injury. Biomed Khim. 2014;60(6):643-50. https://doi.org/10.18097/pbmc2014600643
27. Manigandan K, Manimaran D, Jayaraj RL, et al. Taxifolin curbs NF-κB-mediated Wnt/β- catenin signaling via up-regulating Nrf2 pathway in experimental colon carcinogenesis. Biochimie. 2015; 119: 103-12. https://doi.org/10.1016/j.biochi.2015.10.014
28.Zhou S, Shao Y, Fu J, et al. Characterization and Quantification of Taxifolin Related Flavonoids in Larix olgensis Henry Var. koreana Nakai Extract Analysis and its Antioxidant Activity Assay. Int J Pharmacol. 2018; 14 (4):534–45. https://doi.org/10.3923/ijp.2018.534.545
29.Eken H, Kurnaz E. Biochemical and histopathological evaluation of taxifolin: An experimental study in a rat model of liver ischemia reperfusion injury. J Surg Med. 2019; 3(7): 494-7. https://doi.org/https://doi.org/10.28982/josam.587598