Yıl: 2021 Cilt: 46 Sayı: 3 Sayfa Aralığı: 307 - 315 Metin Dili: İngilizce DOI: 10.1515/tjb-2020-0113 İndeks Tarihi: 20-02-2022

Effect of protocatechuic acid against renal ischemia reperfusion damage on extracellular matrix integrity and related signal pathways

Öz:
Objective: In this study, possible protective effects of protocatechuic acid (PCA) against experimentally-induced acute renal ischemia/reperfusion (I/R) damage in rats, on matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and the associated signal transduction pathways were investigated. Methods: A total of 3–4 month-old, 200–250 g Sprague Dawley rats were divided into groups of five (n=7). A right kidney nephrectomy surgery was conducted to all groups under anesthesia. Rats were administered polyethylene glycol 1 h prior to ischemia (Group I, II) and PCA (Group III, IV, V) intraperitoneally. Forty five minutes before the ischemia during 24 h reperfusion on all rats except those in Group I. At the end of the experiment, blood urea nitrogen (BUN), creatinine values and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) enzyme levels were investigated in blood serum. MMP-2 and MMP-9 gene expression levels were determined by RT-PCR, and p38 and p-p38 protein expression levels Western blotting method. Renal tissue was examined histologically and immunohistochemically. Results: It is assumed that 80 and 120 mg/kg of PCA might have a protective effect against oxidative stress damage caused by renal I/R. Conclusion: In our study, PCA has been shown to modu late the increased expression of MMP-2 and MMP-9 mRNA along with increased oxidative stress during renal I/R, as well as oxidative damage-induced p38 protein expression. It was determined that particularly 120 mg $kg^{−1}$ PCA reduced the renal I/R injury at a rate of 35–45%.
Anahtar Kelime:

Renal iskemi reperfüzyon hasarına karşı protokatekuik asit’in ekstrasellüler matriks bütünlüğü ve ilişkili sinyal ileti yolakları üzerine etkisi

Öz:
Amaç: Bu çalışmada sıçanlarda deneysel olarak oluştu rulan renal iskemi/reperfüzyon (I/R) hasarına karşı proto katekuik asit (PCA)’in, hücre dışı matriks regülasyonunda önemli rolü olan matriks metalloproteinaz-2 (MMP-2), matriks metalloproteinaz-9 (MMP-9) ve ilişkili sinyal ileti yolakları üzerine olası koruyucu etkileri araştırıldı. Materyal ve Metod: Toplam 35 adet 3–4 aylık 200–250 gr ağırlığında Spraque-Dawley cinsi erkek sıçanlar beş gruba ayrıldı (n=7). Anestezi altında tüm gruplara sağ böbrek nefroktomisi gerçekleştirildi. Sıçanlara intraperitonal ola rak 15 gün boyunca günde bir kez olmak üzere polietilen glikol (Grup I, II), ve protokatekuik asit (Grup III, IV) verildi. Grup I hariç tüm gruptaki sıçanlara 45 dakika iskemi 24 saat reperfüzyon işlemi uygulandı. Deney sonunda serumda Kan Üre Nitrojeni (BUN), Kreatinin değerleri ve Süperoksit Dismutaz (SOD), Katalaz (CAT) ve Glutatyon peroksidaz (GPx) enzim seviyelerine bakıldı. MMP-2 ve MMP-9 gen ekspresyon seviyeleri RT-PCR ile p38 ve p-p38 protein ekspresyon seviyeleri Western Blot yön temi ile belirlendi. Renal doku histolojik ve immünohisto kimyasal olarak da incelendi. Sonuçlar: 80 ve 120 mg/kg PCA'nın böbrek ˙I/R ile oluS¸ an oksidatif stres hasarı üzerine koruyucu etkisinin olabilecegi düs ˘ ¸ünülmektedir. Sonuç: çalıs¸mamızda, PCA'nın MMP-2 ve MMP-9 mRNA'- nın artan ekspresyonunu, renal I/R sırasında artmıs¸ oksi datif stresin yanı sıra oksidatif hasara bagl˘ ı p38 protein ekspresyonunu modüle ettigi gösterilmis ˘ ¸tir. Özellikle 120 mg $kg^{−1}$ PCA'nın renal I/R hasarını % 35–45 oranında azalttıg˘ı belirlenmis¸tir.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Yuksel M, Yildar M, Basbug M, Cavdar F, Cıkman O, Aksit H, et al. Does protocatechuic acid, a natural antioxidant, reduce renal ischemia reperfusion injury in rats? Ulus Travma Emergency Surg Derg 2017;23:1–6.
  • 2. Yildar M, Aksit H, Korkut O, Ozyigit MO, Sunay B, Seyrek K. Protective effect of 2-aminoethyl diphenylborinate on acute ischemiareperfusion injury in the rat kidney. J Surg Res 2014;187:683–9.
  • 3. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007;39:44–84.
  • 4. Mecham RP, editor. The extracellular matrix: an overview, biology of extracellular matrix. Berlin Heidelberg: Springer-Verlag; 2014: 1–6 pp.
  • 5. Spinale FG. Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. Physiol Rev 2007;87:1285–342.
  • 6. Massova I, Kotra LP, Fridman R, Mobashery S. Matrix metalloproteinases: structures evolution, and abstract. FASEB J 2017;12:1075–95.
  • 7. Kwiatkowska E, Domanski L, Bober J, Safranow K, Romanowski M, Pawlik A, et al. Urinary metalloproteinases-9 and -2 and their inhibitors TIMP-1 and TIMP-2 are markers of early and long-term graft function after renal transplantation. Kidney Blood Press Res 2016;41:288–97.
  • 8. Cavdar Z, Ural A, Celik A, Arslan S, Terzioglu G, Ozbal S, et al. Protective effects of taurine against renal ischemia/reperfusion injury in rats by inhibition of gelatinases, MMP-2 and MMP-9, and p38 mitogen-activated protein kinase signaling. Biotech Histochem 2017;92:524–35.
  • 9. Spinale FG, Villarreal F. Targeting matrix metalloproteinases in heart disease: lessons from endogenous inhibitors. Biochem Pharmacol 2014;90:7–15.
  • 10. Cheng Z, Limbu MH, Wang Z, Liu J, Liu L, Zhang X, et al. MMP-2 and 9 in chronic kidney disease. Int J Mol Sci 2017;18:776.
  • 11. Zarubin T, Han J. Activation and signaling of the p38 MAP kinase pathway. Cell Res 2005;15:11–8.
  • 12. Weng CJ, Yen GC. Chemopreventive effects of dietary phytochemicals against cancer invasion and metastasis: phenolic acids, monophenol, polyphenol and their derivates. Canc Treat Rev 2012;38:76–87.
  • 13. Tanaka T, Tanaka T, Tanaka M. Potential cancer chemopreventive activity of protocatechuic acid. J Exp Clin Med 2011;3:27–33.
  • 14. Kakkar S, Bais S. A Review on protocatechuic acid and its, pharmacological potential. London: Hindawi Publishing Corporation ISRN Pharmacology; 2014. Volume Article ID 952943.
  • 15. Wang D, Zou T, Yang Y, Yan X, Ling W. Cyanidin-3-O-b-glucoside with the aid of its metabolite protocatechuic acid, reduces monocyte infiltration in apolipoprotein E-deficient mice. Biochem Pharmacol 2011;82:713–9.
  • 16. Min SW, Ryu SN, Kim DH. Anti-inflammatory effects of black rice, cyanidin-3-O-β-D-glycoside, and its metabolites, cyanidin and protocatechuic acid. Int Immunopharm 2010;10:959–66.
  • 17. Lin HH, Chen JH, Chou FP, Wang CJ. Protocatechuic acid inhibits cancer cell metastasis involving the down-regulation of Ras/Akt/ NF-kB pathway and MMP-2 production by targeting RhoB activation. Br J Pharmacol 2011;162:237–54.
  • 18. Waynfort HB, Flecknell PA. Experimental and surgical technique in the rat, 2nd ed. Chapter 29 New York: Academic Press 1994: 174–75 pp.
  • 19. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative CT method. Nature Protocol 2008;3. https://doi. org/10.1038/nprot.2008.73.
  • 20. Salehipour M, Monabbati A, Salahi H, Nikeghbalian S, Bahador A, Marvasti VE, et al. Protective effect of parenteral vitamin E on ischemia-reperfusion injury of rabbit kidney. Urology 2010;75: 858–61.
  • 21. Rosell A, Lo EH. Multiphasic roles for matrix metalloproteinases after stroke. Curr Opin Pharmacol 2008;8:82–9.
  • 22. Ozturk H, Cetinkaya A, Erdogan Duzcu S, Kin Tekce B. Carvacrol attenuates histopathogic and functional impairments induced by bilateral renal ischemia/reperfusion in rats. Biomed Pharmacother 2018; 98: 656–61.
  • 23. Jin X, Zhang Y, Li X, Zhang J. C-type natriuretic peptide ameliorates ischemia/reperfusion-induced acute kidney injury by inhibiting apoptosis and oxidative stress in rats. Life Sci 2014;117:40–5.
  • 24. Sen H, Deniz S, Yedekci AE, Inangil G. Effects of dexpanthenol and N-acetylcysteine pretreatment in rats before renal ischemia/ reperfusion injury. Informa Healthcar 2014;36:1570–4.
  • 25. Behaghel V, Tamareille S, Rabant M, Mirebeau-Prunier D, Biere L, Macchi L, et al. Remote ischemic conditioning in a model of severe renal ischemia-reperfusion injury. Shock 2019;51:795–99.
  • 26. İscan S, Cakır H, Kusku F, Yurekli İ, Eygi B, Donmez K, et al. Investigation the effects of cilostazol and rosuvastatin on kidney and heart: an experimental acute kidney and heart injury model. Turkish J Cardiovas Surg 2017;25:255–63.
  • 27. Cavdar Z, Ozbal S, Celik A, Ergur BU, Güneli E, Ural C, et al. The effects of alpha-lipoic acid on MMP-2 and MMP-9 activities in a rat renal ischemia and reperfusion model. Biotech Histochem 2013; 89:304–14.
  • 28. Jiang H, Chen R, Xue S, Zhu H, Sun X. Protective effects of three remote ischemic conditioning procedures against renal ischemic/reperfusion injury in rat kidneys: a comparative study. Ir J Med Sci 2014;15.
  • 29. Yang S, Chou WP, Pei L. Effects of propofol on renal ischemia/ reperfusion injury in rats. Exp Ther Med 2013;6:1177–118.
  • 30. Senturk H, Yıldız F. Protectıve effects of olea europaea l. (olive) leaf extract against oxidatıve stress injury generated wıth renal ischemıa reperfusıon. J Anim Plant Sci 2018;28:1027–33.
  • 31. Canbek M, Bayramoglu G, Senturk H, Oztopcu Vatan AP, Uyanoglu M, Ceyhan E, et al. The examination of protective effects of gallic acid against damage of oxidative stress during inducedexperimental renal ischemia-reperfusion in experiment. Bratisl Lek Listy 2014;115:557–62.
  • 32. Kunugi S, Shimizu A, Kuwahara N, Du X, Takahashi M, Terasaki Y, et al. Inhibition of matrix metalloproteinases reduces ischemiare-perfusion acute kidney injury. Lab Invest 2011;91:170–180.
  • 33. Ashraf MI, Ebner M, Wallner C, Haller M, Khalid S, Schwelberger H, et al. A p38MAPK/MK2 signaling pathway leading to redox stress, cell death and ischemia/reperfusion injury. Cell Commun Signal 2004;14:6.
  • 34. Lempiäinen J, Finckenberg P, Mervaala E, Sankari S, Levijoki J, Mervaala E, et al. Dexmedetomidine preconditioning ameliorates kidney ischemia-reperfusion injury. Pharma Res 2014;2. https:// doi.org/10.1002/prp2.45.
  • 35. Lv J, Wang X, Liu SY, Liang PF, Feng M, Zhang LL, Xu A.P. Protective effect of Fenofibrate in renal ischemia reperfusion injury Involved in suppressing kinase 2 (JAK2)/transcription 3 (STAT3)/p53 signaling activation. Pathol Biol 2015;63:236–42.
  • 36. Aydin MS, Caliskan A, Kocarslan A, Kocarslan S, Yildiz A, Günay S, et al. Intraperitoneal curcumin decreased lung, renal and heart injury in abdominal aorta ischemia/reperfusion model in rat. Int J Surg 2014;12:601–5.
APA YILDIZ F, ŞENTÜRK H, UYANOĞLU M (2021). Effect of protocatechuic acid against renal ischemia reperfusion damage on extracellular matrix integrity and related signal pathways. , 307 - 315. 10.1515/tjb-2020-0113
Chicago YILDIZ Fatma,ŞENTÜRK Hakan,UYANOĞLU Mustafa Effect of protocatechuic acid against renal ischemia reperfusion damage on extracellular matrix integrity and related signal pathways. (2021): 307 - 315. 10.1515/tjb-2020-0113
MLA YILDIZ Fatma,ŞENTÜRK Hakan,UYANOĞLU Mustafa Effect of protocatechuic acid against renal ischemia reperfusion damage on extracellular matrix integrity and related signal pathways. , 2021, ss.307 - 315. 10.1515/tjb-2020-0113
AMA YILDIZ F,ŞENTÜRK H,UYANOĞLU M Effect of protocatechuic acid against renal ischemia reperfusion damage on extracellular matrix integrity and related signal pathways. . 2021; 307 - 315. 10.1515/tjb-2020-0113
Vancouver YILDIZ F,ŞENTÜRK H,UYANOĞLU M Effect of protocatechuic acid against renal ischemia reperfusion damage on extracellular matrix integrity and related signal pathways. . 2021; 307 - 315. 10.1515/tjb-2020-0113
IEEE YILDIZ F,ŞENTÜRK H,UYANOĞLU M "Effect of protocatechuic acid against renal ischemia reperfusion damage on extracellular matrix integrity and related signal pathways." , ss.307 - 315, 2021. 10.1515/tjb-2020-0113
ISNAD YILDIZ, Fatma vd. "Effect of protocatechuic acid against renal ischemia reperfusion damage on extracellular matrix integrity and related signal pathways". (2021), 307-315. https://doi.org/10.1515/tjb-2020-0113
APA YILDIZ F, ŞENTÜRK H, UYANOĞLU M (2021). Effect of protocatechuic acid against renal ischemia reperfusion damage on extracellular matrix integrity and related signal pathways. Türk Biyokimya Dergisi, 46(3), 307 - 315. 10.1515/tjb-2020-0113
Chicago YILDIZ Fatma,ŞENTÜRK Hakan,UYANOĞLU Mustafa Effect of protocatechuic acid against renal ischemia reperfusion damage on extracellular matrix integrity and related signal pathways. Türk Biyokimya Dergisi 46, no.3 (2021): 307 - 315. 10.1515/tjb-2020-0113
MLA YILDIZ Fatma,ŞENTÜRK Hakan,UYANOĞLU Mustafa Effect of protocatechuic acid against renal ischemia reperfusion damage on extracellular matrix integrity and related signal pathways. Türk Biyokimya Dergisi, vol.46, no.3, 2021, ss.307 - 315. 10.1515/tjb-2020-0113
AMA YILDIZ F,ŞENTÜRK H,UYANOĞLU M Effect of protocatechuic acid against renal ischemia reperfusion damage on extracellular matrix integrity and related signal pathways. Türk Biyokimya Dergisi. 2021; 46(3): 307 - 315. 10.1515/tjb-2020-0113
Vancouver YILDIZ F,ŞENTÜRK H,UYANOĞLU M Effect of protocatechuic acid against renal ischemia reperfusion damage on extracellular matrix integrity and related signal pathways. Türk Biyokimya Dergisi. 2021; 46(3): 307 - 315. 10.1515/tjb-2020-0113
IEEE YILDIZ F,ŞENTÜRK H,UYANOĞLU M "Effect of protocatechuic acid against renal ischemia reperfusion damage on extracellular matrix integrity and related signal pathways." Türk Biyokimya Dergisi, 46, ss.307 - 315, 2021. 10.1515/tjb-2020-0113
ISNAD YILDIZ, Fatma vd. "Effect of protocatechuic acid against renal ischemia reperfusion damage on extracellular matrix integrity and related signal pathways". Türk Biyokimya Dergisi 46/3 (2021), 307-315. https://doi.org/10.1515/tjb-2020-0113