Efficacy of Taxifolin in The Prevention of Renal Injury Due to Liver Ischemia and Reperfusion

Yıl 2023, , 503 - 507, 31.12.2023

Burak Veli Ülger , Fırat Aşır , Metin Varlı , Ercan Gündüz , Hasan Mansur Durgun

https://doi.org/10.36516/jocass.1371823

Öz

Aim: During surgical procedures such as liver resection and transplantation, ischemia/reperfusion (I/R) injury and related complications may occur at a rate of approximately 10%. Our study, we planned to investigate histologically and biochemically the efficacy of Taxifolin in the prevention of renal tissue damage in liver ischemia reperfusion.
Methods: A total of 28 Wistar Albino rats with an average age of 8-10 weeks and weights of 250-300 grams were used in our study. Group 1 (n=7): control group, Group 2 (n=7): Taxifolin group; Taxifolin was administered orally at a dose of 50 mg/kg for 3 weeks, Group 3 (n=7): Liver I/R group, 30 minutes ischemia and 120 minutes reperfusion was performed. Group 4 (n=7): Taxifolin+Liver I/R group.
Results: Kidney tissues of the liver I/R group showed atrophy, degeneration of tubule epithelium and increased TNF-α expression. In addition, deterioration in renal function tests was also monitored in this group. In the Taxifolin+Liver I/R group, a significant difference was observed on both histologic and biochemical basis compared to the Liver I/R group and a positive effect was observed (p<0.05).
Outcome: As a consequence of hepatic ischemia and reperfusion, impairment in the function and histological appearance of renal tissues was observed and Taxifolin was monitored to be effective in eliminating these adverse effects.

Anahtar Kelimeler

liver ischemia and reperfusion, taxifolin, histopathology, immunohistochemistry, oxidative stress

KARACİĞER İSKEMİ VE REPERFÜZYONA BAĞLI BÖBREK HASARLARININ ÖNLENMESİNDE TAKSİFOLİN’İN ETKİNLİĞİ

Öz

Amaç: Karaciğer rezeksiyonu ve transplantasyonu gibi cerrahi işlemler sırasında yaklaşık %10 gibi bir oranda iskemi/reperfüzyon (I/R) hasarı gibi ciddi komplikasyonlar görülebilmektedir. Bu çalışmada böylesi bir komplikasyonun karaciğer dışında böbrek dokusu gibi bir organda meydana getireceği hasarın düzeltilmesinde Taksifolin’in etkinliğini histolojik ve biyokimyasal açıdan incelemeyi planladık.
Yöntem: Çalışmamızda ortalama 8-10 haftalık, 250-300 gram ağırlıklarında toplam 28 adet Wistar Albino cinsi ratlar kullandı. Grup 1 (n=7): kontrol grubu, Grup 2 (n=7): Taksifolin 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): Taksifolin+Karaciğer I/R grubu idi.
Bulgular: Çalışmamızın histolojik bulgularında karaciğer I/R uygulanan grubun böbrek dokularına atrofi, tübül epitelerinde dejenerasyon ve TNF-α ekspresyonlarında artış izlendi. ayrıca bu grubun böbrek fonksiyon testlerinde de bozulmalar izlendi. Tax+Karaciğer I/R grubunda ise, Karaciğer I/R grubuna kıyasla hem histolojik hemde biyokimyasal bazda anlamlı fark olduğu ve olumlu yönde etkilendiği gözlendi (p<0.05).
Sonuç: Karaciğer iskemi ve reperfüzyonu sonucu böbrek dokularının fonksiyonlarında ve histolojik görünümlerinde bozulmalar izlenirken, oluşan bu olumsuz etkilerin giderilmesinde Taksifolin’in etkin olduğu görüldü.

Anahtar Kelimeler

Karaciğer iskemi ve reperfüzyon, Taksifolin, Histopatoloji, İmmunohistokimya, Oksidatif stres

Kaynakça

• 1.Fondevila C, Busuttil Rw, Kupiec-Weglinski Jw. Hepatic Ischemia/Reperfusion Injury A Fresh Look. Exp Mol Pathol. 2003; 74 (2): 86-93. Https://Doi.Org/10.1016/S0014-4800(03)00008-X
• 2.Zhai Y, Petrowsky H, Hong Jc, Et Al. Ischaemia Reperfusion Injury In Liver Transplantation From Bench To Bedside. Nat Rev Gastroenterol Hepatol. 2013; 10 (2): 79-89. Https://Doi.Org/10.1038/Nrgastro.2012.225
• 3. Varadarajan R, Golden-Mason L, Young L, Et Al. Nitric Oxide In Early Ischaemia Reperfusion Injury During Human Orthotopic Liver Transplantation. Transplantation. 2004; 78(2): 250–6. Https://Doi.Org/10.1097/01.Tp.0000128188.45553.8c
• 4.Ugarte-Uribe B, García-Sáez Aj. Membranes In Motion: Mitochondrial Dynamics And Their Role In Apoptosis. Biol Chem. 2014; 395 (3):297-311. Https://Doi.Org/10.1515/Hsz-2013-0234
• 5.Zhang W, Chen C, Wang J, Et Al. Mitophagy In Cardiomyocytes And In Platelets: A Major Mechanism Of Cardioprotection Against Ischemia/Reperfusion Injury. Physiology. 2018; 33 (2): 86-98. Https://Doi.Org/10.1152/Physiol.00030.2017
• 6. Salaritabar A, Darvishi B, Hadjiakhoondi F, Et Al. Therapeutic Potential Of Flavonoids In Inflammatory Bowel Disease: A Comprehensive Review. World J. Gastroenterol. 2017; 23(28): 5097-114. https://doi.org/ 10.3748/Wjg.V23I28.5097
• 7. Yang P, Xu F, Li Hf, Et Al. Detection Of 191 Taxifolin Metabolites And Their Distribution In Rats Using Hplc-Esi-It-Tof-Msn. Molecules. 2016;21(9): 1209. Https://Doi.Org/10.3390/Molecules21091209
• 8.Weidmann Ae. Dihydroquercetin: More Than Just An Impurity? Eur. J. Pharmacol. 2012;684(1-3): 19–26. Https://Doi.Org/10.1016/J.Ejphar.2012.03.035
• 9. Maksimovich Ny, Dremza Ik, Troyan Ei, Et Al. The Correcting Effects Of Dihydroquercetin In Cerebral Ischemia-Reperfusion Injury. Biomeditsinskaya Khimiya. 2014; 60(6): 643-50. Https://Doi.Org/10.18097/Pbmc20146006643
• 10. 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. 2015; 6(2):351-5. Https://Doi.Org/10.4103/0976-9668.160003
• 11. Chaves Jc, Neto Fs, Ikejiri At, Et Al. Period Of Hyperbaric Oxygen Delivery Leads To Different Degrees Of Hepatic Ishemia/Reperfusion Injury In Rats. Transplant Proc. 2016;48(2):516-20. Https://Doi.Org/10.1016/J.Transproceed.2015.11.035
• 12. Kamel Eo, Hassanein Ehm, Ahmed Ma, Et Al. Perindopril Ameliorates Hepatic Ischemia Reperfusion Injury Via Regulation Of Nf-Kappab-P65/Tlr-4, Jak1/Stat-3, Nrf-2, And Pi3k/Akt/ Mtor Signaling Pathways. Anat Rec (Hoboken). 2020;303(7):1935-1949. Https://Doi.Org/10.1002/Ar.24292. Epub 2019 Nov 6.
• 13. Mahmoud Ar, Ali Fem, Abd-Elhamid Th, Et Al. Coenzyme Q10 Protects Hepatocytes From Ischemia Reperfusioninduced Apoptosis And Oxidative Stress Via Regulation Of Bax/Bcl-2/ Puma And Nrf-2/Foxo-3/Sirt-1 Signaling Pathways. Tissue Cell. 2019;60:1-13. Https://Doi.Org/10.1016/J.Tice.2019.07.007.
• 14. Bedir F, Kocatürk H, Yapanoğlu T, Et Al. Protective Effect Of Taxifolin Against Prooxidant And Proinflammatory Kidney Damage Associated With Acrylamide In Rats. Biomed Pharmacother. 2021;139:111660. Https://Doi.Org/10.1016/J.Biopha.2021.111660.
• 15. Satoh K. Serum Lipid Peroxide In Cerebrovascular Disorders Determined By A New Colorimetric Method. Clin Chim Acta. 197815;90(1):37-43. Https://Doi.Org/10.1016/0009-8981(78)90081-5.
• 16. Gündüz E, Yildizhan E, Yaman M, Et Al. Investigation Of The Protective Effects Of Boric Acid Against Hepatotoxic And Nephrotoxic Injury Induced By Acyrlamide In Rats. Int. J. Morphol. 2023; 41(2):368-73.
• 17. Yildizhan E, Ozesmer H, Inan Mm, Et Al. Protective Effects Of Anise In Prevention Of Cerebral Ischemia Reperfusion Injury In Rats. Polish Journal Of Veterinary Sciences. 2023; 26(3): 343–7. Https://Doi.Org/10.24425/Pjvs.2023.145038
• 18. Chatterjee Pk; Cuzzocrea S, Brown Pa, Et Al. Tempol, A Membranepermeable Radical Scavenger, Reduces Oxidant Stress-Mediated Renal Dysfunction And Injury In The Rat. Kidney Int. Kidney Int. 2000;58(2):658-73. https://doi.org/ 10.1046/J.1523-1755.2000.00212.X.
• 19. Yıldızhan E, Ülger Bv, Akkuş M, Et Al. Rosmarinic Acid Ameliorates Deltametrin Induced Hepatotoxicity And Nephrotoxicity. Med Records. 2023;5(2):400-5. Https://Doi.Org/10.37990/Medr.1197782
• 20.Yildizhan E, Ulger Bv, Akkus M, Et Al. Comparison Of Topical Sucralfate With Dexpanthenol In Rat Wound Model. Int J Exp Path. 2022;00:1–7. https://doi.org/ 10.1111/Iep.12441.
• 21. Nastos C, Kalimeris K, Papoutsidakis N, Et Al. Global Consequences Of Liver Ischemia/Reperfusion Injury. Oxid Med Cell Longev. 2014:906–965. Https://Doi.Org/10.1155/2014/906965
• 22. Yap Sc, Lee Ht. Acute Kidney Injury And Extrarenal Organ Dysfunction: New Concepts And Experimental Evidence. Anesthesiology. 2012;116:1139–48. https://doi.org/ 10.1097/Aln.0b013e31824f951b
• 23. Doi K, Rabb H. Impact Of Acute Kidney Injury On Distant Organ Function: Recent Findings And Potential Therapeutic Targets. Kidney Int. 2016;89:555–64. https://doi.org/10.1016/J.Kint.2015.11.019
• 24. Husain-Syed F, Rosner Mh, Ronco C. Distant Organ Dysfunction In Acute Kidney Injury. Acta Physiol. Acta Physiol (Oxf). 2020;228(2):E13357. Https://Doi.Org/10.1111/Apha.13357
• 25. Lee Ht, Park Sw, Kim M, Et Al. Acute Kidney Injury After Hepatic Ischemia And Reperfusion Injury In Mice. Lab Invest. 2009;89(2):196–208. Https://Doi.Org/10.1038/Labinvest.
• 26. Serteser M, Koken T, Kahraman A, Et Al. Changes In Hepatic Tnf-Alpha Levels, Antioxidant Status, And Oxidation Products After Renal Ischemia/Reperfusion Injury In Mice. J Surg Res. 2002;107(2):234–40. Https://Doi.Org/10.1006/Jsre.2002.6513.
• 27. Tanaka Y, Maher Jm, Chen C, Et Al. Hepatic Ischemia Reperfusion Induces Renal Heme Oxygenase-1 Via Nf-E2-Related Factor 2 In Rats And Mice. Mol Pharmacol. 2007;71(3):817–25. Https://Doi.Org/10.1124/Mol.106.029033.
• 28. Li J, Li L, Wang S, Et Al. Resveratrol Alleviates Inflammatory Responses And Oxidative Stress In Rat Kidney Ischemia-Reperfusion Injury And H2o2 Induced Nrk-52e Cells Via The Nrf2/Tlr4/Nf-Κb Pathway. Cell Physiol. Biochem. 2018;45(4):1677-1689. Https://Doi.Org/10.1159/000487735
• 29. Ince S, Kucukkurt I, Demirel Hh, Et Al. Boron, A Trace Mineral, Alleviates Gentamicin-Induced Nephrotoxicity In Rats. Biol Trace Elem Res. 2020;195(2):515-524. Https://Doi.Org/10.1007/S12011-019-01875-4.
• 30. Ha H, Yu Mr, Choi Yj, Et Al. Role Of High Glucose-Induced Nuclear Factor-Κb Activation In Monocyte Chemoattractant Protein-1 Expression By Mesangial Cells. J Am Soc Nephrol. 2002;13(4):894-902. Https://Doi.Org/10.1681/Asn.V134894.
• 31. Rice-Evans Ca, Miller Nj, Paganga G. Structure-Antioxidant Activity Relationships Of Flavonoids And Phenolic Acids. Free Radic Biol Med. 1996;20(7):933-56. Https://Doi.Org/10.1016/0891-5849(95)02227-9.
• 32. Ahiskali I, Pinar Cl, Kiki M, Et Al. Effect Of Taxifolin On Methanol-Induced Oxidative And Inflammatory Optic Nerve Damage In Rats. Cutan Ocul Toxicol. 2019;38(4):384-9. Https://Doi.Org/10.1080/15569527.2019.1637348.
• 33. Begenik H, Soyoral Yu, Erkoc R, Et Al. Serum Malondialdehyde Levels, Myeloperoxidase And Catalase Activities In Patients With Nephrotic Syndrome. Redox Rep. 2013;18(3):107–12. Https://Doi.Org/10.1179/1351000213y.0000000048
• 34. Elhelaly A, Albasher S. et al. Protective Effects Of Hesperidin And Diosmin Against Acrylamide-Induced Liver, Kidney, And Brain Oxidative Damage In Rats. Environ Sci Pollut Res Int. 2019;26(34):35151-35162. Https://Doi.Org/10.1007/S11356-019-06660-3.