CCl4-nefrotoksisitesinde L-karnitin’in etkileri: Glomeruler nefrin ve HIF-1alfa ekspresyonlarının immunohistokimyasal değerlendirilmesi

Amaç: Bu çalışmada glomerül yapısındaki nefrin ve hipoksi indüklenebilir faktör-1alfa ekspresyonları aracılığıyla karbontetraklorid (CCl4) toksisitesi sonrası L-karnitin’in etkilerinin gösterilmesini amaçladık. Gereç ve Yöntem: 40 adet Sprague dawley erkek sıçan 5 gruba (n=8) ayrıldı. Grup I: Kontrol grubu; 0.2 ml zeytinyağı intraperitoneal (ip) haftada 2 kez, Grup II: L-karnitin grubu; 200 mg/kg L-karnitin (ip) haftada 2 kez, Grup III: CCl4 group; 0.2 ml CCl4 (ip) haftada 2 kez 6 hafta boyunca, Grup IV: L-karnitin + CCl4 grubu, haftada 2 kez CCl4 uygulamasından önce 200 mg/kg ip L-karnitin, Grup V: CCl4 + L-karnitin grubu, haftada 2 kez CCl4 uygulamasından 1 saat sonra 200 mg/kg ip L-karnitin. Böbrek doku kesitlerine nefrin ve HIF-1α ekspresyonunu göstermek için immunohistokimya boyama uygulandı. Proteinlerin ekspresyon yoğunlukları ImageJ programında ölçüldü.Bulgular: Nefrin ekspresyonu diğer gruplar ile kıyaslandığında Grup III’de anlamlı olarak arttı. HIF-1α ekspresyonu yalnızca Grup I ve Grup III arasında anlamlı şekilde arttı. Proteinlerin ekspresyon yoğunlukları L-karnitin-tedavili gruplarda kontrol grubuna benzerdi.Sonuç: L-karnitin böbrek glomerulusunda CCl4 toksisitesine karşı hem koruyucu hem tedavi edici etkilere sahiptir.

L-carnitine effects in CCl4-nephrotoxicity: Immunohistochemical evaluation of glomerular nephrin and HIF-1alpha expressions

Purpose: In this study, we aimed to demonstrate the effects of L-carnitine after carbontetrachloride (CCl4) toxicity through nephrin and Hypoxia inducible factor-1 alpha (HIF-1α) expressions in the glomerular structure.Materials and Methods: Forty male Sprague dawley rats were divided into 5 groups with animals in each group. Group I: Control group; 0.2 ml olive oil intraperitoneal (ip) twice weekly, Group II: L-carnitine group; 200 mg/kg L-carnitine (ip) twice a week, Group III: CCl4 group; 0.2 ml CCl4 (ip) twice a week for 6 weeks, Group IV: L-carnitine + CCl4 group, 200 mg/kg ip L-carnitine 24 hours before CCl4 twice a week, Group V: CCl4 + L-carnitine group; 200 mg/kg L-carnitine half an hour after CCl4 twice a week. Immunohistochemical staining was performed on kidney tissue sections to show nephrin and HIF-1α expression. Expression densities of the proteins were measured by ImageJ program.Results: Nephrin expression was significantly increased in Group III compared to other groups. There was a significant increase in HIF-1α expression only between Group I and Group III. Expression densities of proteins in L-carnitine-treated groups were similar to control.Conclusion: L-carnitine has both protective and therapeutic effects against CCl4 toxicity in renal glomeruli.

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  • 1. Rahmouni F, Daoud S, Rebai T. Teucrium polium attenuates carbon tetrachloride-induced toxicity in the male reproductive system of rats. Andrologia. 2019;51:e13182.
  • 2. Berthelot P. Mechanisms and prediction of druginduced liver disease. Gut. 1973;14:332-9.
  • 3. Sahreen S, Khan MR, Khan RA. Ameliorating effect of various fractions of Rumex hastatus roots against hepato- and testicular toxicity caused by CCl4. Oxid Med Cell Longev. 2013;2013:325406.
  • 4. Sahreen S, Khan MR, Khan RA, Alkreathy HM. Cardioprotective role of leaves extracts of Carissa opaca against CCl4 induced toxicity in rats. BMC Res Notes. 2014;7:224.
  • 5. Khalil I, Ghani M, Khan MR, Akbar F. Evaluation of biological activities and in vivo amelioration of CCl4 induced toxicity in lung and kidney with Abutilon pannosum (G.Forst.) Schltdl. in rat. J Ethnopharmacol. 2019;15:112395.
  • 6. El-Faras AA, Sadek IA, Ali YE, Khalil M, Mussa EB. Protective effects of Vitamin E on CCl4-induced testicular toxicity in male rats. Physiol Int. 2016;103:157-68.
  • 7. Demirdag K, Bahcecioglu IH, Ozercan IH, Ozden M, Yilmaz S, Kalkan A. Role of L-carnitine in the prevention of acute liver damage induced by carbon tetrachloride in rats. J Gastroenterol Hepatol. 2004;19:333-8.
  • 8. Demiroren K, Dogan Y, Kocamaz H, Ozercan IH, Ilhan S, Ustundag B, et al. Protective effects of Lcarnitine, N-acetylcysteine and genistein in an experimental model of liver fibrosis. Clin Res Hepatol Gastroenterol. 2014;38:63-72.
  • 9. Cetinkaya A, Kantarceken B, Bulbuloglu E, Kurutas EB, Ciralik H, Atli Y. The effects of L-carnitine and N-acetylcysteine on carbontetrachloride induced acute liver damage in rats. Bratisl Lek Listy. 2013;114:682-8.
  • 10. Aleisa AM, Al-Majed AA, Al-Yahya AA, Al-Rejaie SS, Bakheet SA, Al-Shabanah OA et al. Reversal of cisplatin-induced carnitine deficiency and energy starvation by propionyl-L-carnitine in rat kidney tissues. Clin Exp Pharmacol Physiol. 2007;34:1252-9.
  • 11. Popovic D, Kocic G, Katic V, Jovic Z, Zarubica A, Jankovic Velickovic L et al. Protective effects of anthocyanins from bilberry extract in rats exposed to nephrotoxic effects of carbon tetrachloride. Chem Biol Interact. 2019;304:61-72.
  • 12. Sachs N, Sonnenberg A. Cell-matrix adhesion of podocytes in physiology and disease. Nat Rev Nephrol. 2013;9:200-10.
  • 13. Hirabayashi S, Mori H, Kansaku A, Kurihara H, Sakai T, Shimizu F et al. MAGI-1 is a component of the glomerular slit diaphragm that is tightly associated with nephrin. Lab Invest. 2005;85:1528-43.
  • 14. Jones N, New LA, Fortino MA, Eremina V, Ruston J, Blasutig IM et al. Nck proteins maintain the adult glomerular filtration barrier. J Am Soc Nephrol. 2009;20:1533-43.
  • 15. Greka A, Mundel P. Cell biology and pathology of podocytes. Annu Rev Physiol. 2012;74:299-323.
  • 16. Furness PN, Hall LL, Shaw JA, Pringle JH. Glomerular expression of nephrin is decreased in acquired human nephrotic syndrome. Nephrol Dial Transplant. 1999;14:1234-7.
  • 17. Luimula P, Aaltonen P, Ahola H, Palmen T, Holthofer H. Alternatively spliced nephrin in experimental glomerular disease of the rat. Pediatr Res. 2000;48:759-62.
  • 18. Narita I, Shimada M, Yamabe H, Kinjo T, Tanno T, Nishizaki K et al. NF-kappaB-dependent increase in tissue factor expression is responsible for hypoxic podocyte injury. Clin Exp Nephrol. 2016;20:679-88.
  • 19. Eckardt KU, Bernhardt WM, Weidemann A, Warnecke C, Rosenberger C, Wiesener MS et al. Role of hypoxia in the pathogenesis of renal disease. Kidney Int Suppl. 2005;99:46-51.
  • 20. Karabulut D, Ulusoy HB, Kaymak E, Sonmez MF. Therapeutic effects of pentoxifylline on diabetic heart tissue via NOS. Anatol J Cardiol. 2016;16:310-5.
  • 21. Luo R, Zhang W, Zhao C, Zhang Y, Wu H, Jin J et al. Elevated Endothelial Hypoxia-Inducible Factor1alpha Contributes to Glomerular Injury and Promotes Hypertensive Chronic Kidney Disease. Hypertension. 2015;66:75-84.
  • 22. Alomari G, Al-Trad B, Hamdan S, Aljabali A, AlZoubi M, Bataineh N, et al. Gold nanoparticles attenuate albuminuria by inhibiting podocyte injury in a rat model of diabetic nephropathy. Drug Deliv Transl Res. 2019;21.
  • 23. Pavenstadt H, Kriz W, Kretzler M. Cell biology of the glomerular podocyte. Physiol Rev. 2003;83:253-307.
  • 24. Furukawa T, Ohno S, Oguchi H, Hora K, Tokunaga S, Furuta S. Morphometric study of glomerular slit diaphragms fixed by rapid-freezing and freezesubstitution. Kidney Int. 1991;40:621-4.
  • 25. Aaltonen P, Luimula P, Astrom E, Palmen T, Gronholm T, Palojoki E et al. Changes in the expression of nephrin gene and protein in experimental diabetic nephropathy. Lab Invest. 2001;81:1185-90.
  • 26. Shukla R, Pandey N, Banerjee S, Tripathi YB. Effect of extract of Pueraria tuberosa on expression of hypoxia inducible factor-1alpha and vascular endothelial growth factor in kidney of diabetic rats. Biomed Pharmacother. 2017;93:276-85.
  • 27. Sun H-K, Lee YM, Han KH, Kim H-S, Ahn S-H, Han S-Y. Phosphodiesterase inhibitor improves renal tubulointerstitial hypoxia of the diabetic rat kidney. The Korean journal of internal medicine. 2012;27:163.
  • 28. Nakuluri K, Mukhi D, Mungamuri SK, Pasupulati AK. Stabilization of hypoxia-inducible factor 1alpha by cobalt chloride impairs podocyte morphology and slit-diaphragm function. J Cell Biochem. 2018;1.
  • 29. Nordquist L, Friederich-Persson M, Fasching A, Liss P, Shoji K, Nangaku M, et al. Activation of hypoxiainducible factors prevents diabetic nephropathy. Journal of the American Society of Nephrology. 2015;26:328-38.
  • 30. Dallatu MK, Nwokocha E, Agu N, Myung C, Newaz MA, Garcia G, et al. The role of hypoxia-inducible factor/prolyl hydroxylation pathway in deoxycorticosterone acetate/salt hypertension in the rat. J Hypertens (Los Angel). 2014;3(6).
  • 31. Kaukinen A, Kuusniemi AM, Lautenschlager I, Jalanko H. Glomerular endothelium in kidneys with congenital nephrotic syndrome of the Finnish type (NPHS1). Nephrol Dial Transplant. 2008;23:1224-32.
Cukurova Medical Journal-Cover
  • ISSN: 2602-3032
  • Yayın Aralığı: Yılda 4 Sayı
  • Başlangıç: 1976
  • Yayıncı: Çukurova Üniversitesi Tıp Fakültesi
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