The Investigation of the Effects of Enalapril and Losartan on Ghrelin Immunoreactivity in Kidney of Streptozotocin-Induced Diabetic Rats

Abstract

Objective: The aim of this study was to examine the effects of enalapril and losartan on ghrelin immunoreactivity in the kidney tissues of rats with streptozotocin (STZ) induced diabetes. Materials and Methods: The study involved 28 Wistar albino rats. The rats were allocated to four groups: control group (n=7), diabetes (DM) group (n=7), DM + enalapril group (n=7) and DM + losartan group (n=7). DM, DM + enalapril and DM + losartan groups were administered a single dose of 50 mg/kg of STZ, intraperitoneally. The rats in the treatment groups were orally administered 5 mg/kg/day of enalapril and 10 mg/kg/day of losartan, starting with the onset of diabetes. At the end of the fourth week of the experiment, rats were decapitated. Kidney tissues collected from the animals were processed by using routine histological techniques. Ghrelin immunoreactivity was determined by avidin-biotin-peroxidase method. Results: Ghrelin immunoreactivity in the distal tubules was moderate (++) in the control group and severe (+++) in the diabetic group. In the distal tubules of the treatment groups, ghrelin immunoreactivity was observed to be moderate (++), similar to the control group. Conclusion: It was determined that enalapril and losartan were effective against ghrelin immunoreactivity in the diabetic rat kidney tissues.

Keywords

• Diabetes mellitus, Enalapril, Losartan, Ghrelin

Deneysel Diyabetik Sıçan Böbrek Dokusunda Enalapril ve Losartan'ın Ghrelin İmmunreaktivitesi Üzerine Etkilerinin İncelenmesi

Abstract

Amaç: Bu çalışmada, streptozotosin (STZ) ile deneysel olarak oluşturulan diyabetik sıçanların böbrek dokusunda, enalapril ve losartan'ın ghrelin immunreaktivitesi üzerine etkilerinin incelenmesi amaçlanmıştır. Gereç ve Yöntem: Çalışmada 28 adet erişkin, dişi Wistar albino cinsi sıçan kullanıldı. Deney hayvanları Kontrol grubu (n=7), diyabetik (DM) grup (n=7), DM + Enalapril (n=7) ve DM +Losartan (n=7) olmak üzere dört gruba ayrıldı. Diyabetik, DM + Enalapril ve DM +Losartan gruplarına 50 mg/kg olacak şekilde tek doz STZ (Sigma Chemical Co Louis Missouri) 0,1 M Fosfat-sitrat tamponunda ( pH: 4,5) çözdürülerek intraperitoneal olarak uygulandı. Tedavi gruplarındaki sıçanlara diyabetin başlangıcından itibaren 5 mg/kg/gün Enalapril ve 10 mg/kg/gün losartan oral olarak verildi. Deneyin 4. haftasının sonunda tüm gruptaki ratlar dekapite edildiler. Deney hayvanlarından alınan böbrek dokularına rutin histolojik teknikler uygulandı. Avidin-biotin-peroksidaz yöntemi ile ghrelin immünreaktivitesi belirlendi. Bulgular: Böbrek dokusunda distal tübüllerde kontrol grubunda orta şiddette (++), diyabetik grupta ise şiddetli (+++) ghrelin immünreaktivitesi gözlendi. Tedavi gruplarında ise distal tübüllerde her iki grupta da kontrol grubuna benzer şekilde orta şiddette (++) ghrelin immünreaktivitesi izlendi. Sonuç: Diyabetik sıçanların böbrek dokusunda enalapril ve losartanın ghrelin immunreaktivitesi üzerine etkili olduğu belirlendi.

Keywords

• Diabetes mellitus, Enalapril, Losartan, Ghrelin

References

1. Powers AC. Diabetes Mellitus. In: Kasper DL, Fauci AS, Longo DL, Braunwald E, Hauser SL, Jameson JL, (eds). Harrison’s principles of Internal Medicine. 16th ed. McGraw Hill 2005; 2152-80.
2. Kahn CR, Weir GC, King GL, Jacobson AM, Moses AC, Smith RJ. Joslin’s diabetes mellitus. fourteenth edition. Boston: Lippincott Williams and Wilkins, 2005; 331- 8.
3. Rahimi R, Nikfar S, Larijani B, Abdollahi M. A review on the role of antioxidants in the management of diabetes and its complications. Biomed Pharmacother 2005; 59: 365–73.
4. Cooper ME. Interaction of metabolic and hemodynamic factors in mediating experimental diabetic nephropathy. Diabetologia 2001; 44: 1957–72.
5. Taniyama Y, Griendling KK. Reactive oxygen species in the vasculature: Molecular and cellular mechanisms. Hypertension 2003, 42: 1075-81.
6. Touyz RM. Reactive oxygen species and angiotensin II signaling in vascular cells implications in cardiovascular disease. Braz J Med Biol Res 2004, 37: 1263-73.
7. Touyz RM, Schiffrin EL. Ang II-stimulated superoxide production is mediated via phospholipase D in human vascular smooth muscle cells. Hypertension 1999; 34: 976-82.
8. Onozato ML, Tojo A, Goto A, Fujita T, Wilcox CS. Oxidative stress and nitric oxide synthase in rat diabetic nephropathy: effects of ACEI and ARB. Kidney Int 2002; 61: 18 -94.

9. Berry C, Anderson N, Kirk AJ, Dominiczak AF, McMurray JJ. Renin angiotensin system inhibition is associated with reduced free radical concentrations in arteries of patients with coronary heart disease. Heart 2001, 86: 217-20.
10. Johansen JS, Harris AK, Rychly DJ and Ergul A. Oxidative stress and the use of antioxidants in diabetes: Linking basic science to clinical practice. Cardiovascular Diabetology 2005, 4:
11. Fan Q, Liao J, Kobayashi M, et al. Candesartan reduced advanced glycation end-products 56 accumulation and diminished nitro- oxidative stress in type 2 diabetic KK/Ta mice. Nephrol Dial Transplant 2004; 19: 3012-20.
12. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-relasing acylatedpeptide from stomach. Nature 1999; 402: 656-60.
13. Kojima M, Kangawa K. Ghrelin: structure and function. Physiol Rev 2005; 85: 495-522.
14. Aydın S. Discovery of ghrelin hormone: research and clinical applications. Turk J Biochem 2007; 32: 76-89.
15. Masaoka T, Suzuki H, Hosoda H, et al. Enhanced plasma ghrelin levels in rats with streptozotocin-induced diabetes. FEBS Lett 2003; 541: 64-8.
16. Kumar V, Cotran RS, Robbins SL. Temel patoloji, Prof. Dr. Uğur Çevikbaş. 6. Ed, Nobel Tıp Kitabevi, İstanbul, 2000; 511Osterby R, Asplund J, Bangstad HJ, Nyberg G, Rudberg S, Viberti GC, Walker JD. Neovascularization at the vascular pole region in diabetic glomerulopathy. Nephrol Dial Transplant 1999; 14: 348-52.
17. Ronco C, La Greca G. Vitamin E bonded membrane, a further step in dialysis optizimation. Contrib Nephrol 1999; 127: 1–
18. Sies H. Oxidants and antioxidants. Exp Physiol 1997; 82: 291
19. Altan N, Dinçel AS, Koca C. Diabetes mellitus and oxidative stress. Turk J Biochem 2006; 31: 51-6.
20. Esposito C, Liu ZH, Striker GE, et al. Inhibition of diabetic nephropathy by a GH antagonist: A molecular analysis. Kidney Int 1996; 50: 506-14.
21. Lundbaek K, Christensen NJ, Jensen VA, et al. Diabetes, diabetic angiopathy, and growth hormone. Lancet 1970; 2: 131Mori K, Yoshimoto A, Takaya K, et al. Kidney produces a novel acylated peptide, ghrelin. FEBS Lett 2000; 486: 213-6.
22. Kuloglu T and Dabak DO. Determination of ghrelin ımmunoreactivity in kidney tisues of diabetic rats. Renal Failure 2009; 31: 562-6.
23. Yoshimoto A, Mori K, Sugawara A. Plasma ghrelin and desacyl ghrelin concentrations in renal failure. J Am Soc Nephrol 2002; 13: 2748-52.
24. Başkal N. Diabetes mellitus’un sınıflandırılması. Erdoğan G. (ed), Endokrinoloji Temel ve Klinik, İkinci Baskı, Ankara: Medical Network & Nobel, 2005; 342-8.
25. Büyükdevrim AS, Büyükbeşe MA, Davutoğlu M. Diabetik nefropati. Klinik moleküler patogenez klasik ve moleküler tedavi. İstanbul: Turgut Yayıncılık, 2005; 432-529, 136-342.
26. Tuğrul A. Diabetik nefropati. Trakya Üniversitesi Tıp Fakültesi Dergisi, 2002; 19: 113-21.
27. Locatelli F, Canaud B, Eckardt KU, Stenvinkel P, Wanner C, Zoccali C. Oxidative stress in end-stage renal disease: an emerging threat to patient outcome, Consensus Paper. Nephrol Dial Transplant. 2003; 18: 1272-80.
28. Flyvbjerg A. Role of growth hormone, insulin-like growth factors (IGFs) and IGF-binding proteins in the renal complications of diabetes. Kidney Int Sup 1997; 60: 12-9.
29. Segev Y, Landau D, Rasch R, Flyvbjerg A, Phillip M. Growth hormone receptor antagonism prevents early renal changes in nonobese diabetic mice. J Am Soc Nephrol 1999; 10: 2374-81.
30. Flyvbjerg A, Bennett WF, Rasch R, Kopchick JJ, Scarlett JA. Inhibitory effect of a growth hormone receptor antagonist (G120K-PEG) on renal enlargement, glomerular hypertrophy, and urinary albumin excretion in experimental diabetes in mice. Diabetes 1999; 48: 377-82.
31. Küçüksu M. Metabolik Sendrom oluşturulmuş ratlarda enalapril maleate’ın ghrelin ve obestatin üzerine etkisi. Uzmanlık Tezi, 2009; 61-74. Gönderilme Tarihi: 09.07.2012