Deneysel Diyabetik Sıçan Böbrek Dokusunda TRPV1 ve TRPM2 Kanallarına Losartanın Etkileri

ÖZET Amaç: Hücrenin canlılığını koruyabilmesi ve hücresel fonksiyonların devam ettirilmesinde iyon kanalları önemli role sahiptir. Bu çalışmada deneysel diyabet oluşturulan sıçanların böbrek dokusundaki transient reseptör potansiyel vanniloid (TRPV1) ve transient reseptör potansiyel melastatin 2 (TRPM2) kanallarına losartanın etkilerinin incelenmesi amaçlanmıştır. Gereç ve Yöntem: Çalışmada, 24 adet 8-10 haftalık Wistar albino cinsi erkek sıçanlar kullanıldı. Deney hayvanları 4 eşit gruba ayrıldı. Kontrol grubuna hiçbir uygulama yapılmadı. Tampon grubuna sadece fosfat-sitrat tamponu intraperitoneal (i.p) olarak enjekte edildi. Diyabet grubuna 50 mg/kg streptozotosin (STZ) fosfat-sitrat tamponunda çözdürülerek i.p olarak uygulandı. Diyabet + losartan grubuna ise 50 mg/kg STZ i.p olarak uygulanmasından sonra diyabetin oluşumunu takiben losartan 10 mg/kg/gün oral olarak verildi. Deney sonunda sıçanlar dekapite edildi ve böbrek dokuları çıkartıldı. Rutin takip işlemi ile dokular parafin bloklara gömüldü. Bloklardan alınan kesitlere TRPV1 ve TRPM2 immünreaktivitesi için avidin-biotin-peroksidaz yöntemi uygulandı. Bulgular: TRPV1 immünreaktivitesi kontrol ve tampon grubunda glomerüllerde +3 yaygınlığında gözlendi. Kontrol gruplarıyla karşılaştırıldığında diyabet grubunda TRPV1 immünreaktivitesinde azalma izlendi ve +1 yaygınlığında değerlendirildi. Diyabet grubu ile karşılaştırıldığında losartan grubunda TRPV1 immünreaktivitesinde değişiklik gözlenmedi. TRPM2 immünreaktivitesi ise kontrol ve tampon grubunda tübüllerde +1 şiddetinde izlendi. Kontrol gruplarıyla karşılaştırıldığında diyabet grubunda TRPM2 immünreaktivitesinde artış gözlendi ve +3 şiddetinde değerlendirildi. Diyabet grubu ile karşılaştırıldığında losartan grubunda TRPM2 immünreaktivitesinde azalma vardı. Sonuç: Deneysel diyabetin sıçan böbrek dokusunda TRPV1 immünreaktivitesini azalttığı, TRPM2 immünreaktivitesini arttırdığı gözlendi. Bu sonuçlar diyabetik nefropatinin patofizyolojik mekanizmasına TRPV1 ve TRPM2 kanallarının katılabileceğini düşündürmektedir.

The Effects of Losartan on TRPV1 and TRPM2 Channels at Diabetic Rat Kidney Tissue

Objective: Ion channels have important roles in maintaining cell viability and cellular functions. The aim of this study is to determine the effects of losartan on TRPV1 and TRPM2 ion channels at experimental diabetes mellitus kidney tissues in rats. Material and Method: We used 24 male 8-10 weeks old Wistar albino rats. Rats were divided into 4 groups. No application was made to control group. To buffer group, only phosphate-citrate buffer was injected intraperitoneally. To diabetic group 50 mg/kg streptozocin (STZ) that was dissolved in phosphate-citrate buffer was injected. In diabetes + losartan group, 50 mg/kg STZ was injected and losartan was given 10 mg/kg/day orally after development of diabetes. Finally rats were decapitated and kidney tissues were removed. With routine procedures, tissues were embedded in paraphine blockes. For TRPV1 ve TRPM2 immunreactivity ‘‘avidin-biotin-peroxidase’’ method was applied. Results: TRPV1 immunreactivity was at +3 diffusiveness in glomeruli at control and buffer group. In comparison with control group, TRPV1 immunreactivity was decreased at diabetic group as +1 diffusiveness. There was no alteration at TRPV1 immunreactivity between diabetic group and losartan group. TRPM2 immunreactivity was observed +1 intensity in tubules at control and buffer group. In comparison with control group, TRPM2 immunreactivity was increased at diabetic group as +3 intensity. In comparison with diabetic group, TRPM2 immunreactivity was decreased at losartan group. Conclusion: We observed that diabetes decreases TRPV1 immunreactivity, increases TRPM2 immunreactivity at rat kidney tissue. These results suggest that TRPV1 and TRPM2 channels can parcipate to pathophysiological mechanisms of diabetic nephropathy.

___

  • KAYNAKLAR 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. International Diabetes Federation. IDF Diabetes Atlas, 5th edition. Update. Brussels, Belgium: International Diabetes Federation, 2012. Go AS, Mozaffarian D, Roger V, et al. American heart association statistics committee and stroke statistics subcommittee. Heart disease and stroke statistics – 2013 update: a report from the American Heart Association. Circulation 2013; 127: 6-245. International Diabetes Federation. Diabetes Atlas. 5th ed. Brussels, Belgium: International Diabetes Federation; 2011. Campos C. Chronic hyperglycemia and glucose toxicity: pathology and clinical sequelae. Postgrad Med 2012; 124: 90- 7. Rahman S, Rahman T, Ismail AA, Rashid AR. Diabetes- associated macrovasculopathy: pathophysiology and pathogenesis. Diabetes Obes Metab 2007; 9: 767-80. Evrankaya R. Diabetik nefropati. Özata M ve Yönem A. (ed), Endokrinoloji metabolizma ve diabet. Birinci Baskı. İstanbul: Medikal Yayıncılık, 2006; 359-66. Pitkanen OM, Martin JM, Hallman M, Akerblom HK, Sariola H, Andersson SM. Free radical activity during development of insulin-dependent diabetes mellitus in the rat. Life Sci 1992; 50: 335-9. Naziroğlu M, Lückhoff A. Effects of antioxidants on calcium influx through TRPM2channels in transfected cells activated by hydrogen peroxide. J Neurol Sci 2008; 270: 152-8. Nishida M, Hara Y, Inoue R, Mori Y. TRP channels: formation of signal complex and regulation of cellular functions. Nippon Yakurigaku Zasshi 2003; 121: 223-32. Feng NH, Lee HH, Shiang JC, Ma MC. Transient receptor potential vanilloid type 1 channels act as mechanoreceptors and cause substance P release and sensory activation in rat kidneys. Am J Physiol Renal Physiol 2008; 294: 316-25. Rayamajhi S, Contractor T, Wang DH. The potential of TRPV1 agonists for treating ischemia/reperfusion-induced renal injuries. Curr Opin Investig Drugs 2009; 10: 963-70. Rajagopalan S, Kurz S, Münzel T, et al. Angiotensin II- mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J Clin Invest 1996; 97: 1916-23. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. Arslan M. Diabetes mellitusta tanı ve sınıflandırma. İliçin G, Biberoğlu K, Süleymanlar G, Ünal S (editors). 2. Baskı, 2003; 2279-82. Kumar V, Cotran RS, Robbins SL. Temel Patoloji, Çevikbaş U (editors). İstanbul Nobel Tıp Kitabevi, 2003; 635-55. Van Dam PS, Bravenboer B. Oxidative stres and antioxidant treatment in diabetic neuropathy. Neuroscience Research Communications 1997; 21: 41-8. Gutteridge JMC, Halliwell B. Antioxidants in nutrition, health, and disease. First edition, New York, Oxford University Press 1994. Halliwell B. Oxidants and central nervous system: Some fundamental questions. Is oxidant damage relevant to Parkinson's disease, Alzheimer's disease, traumatic injury or stroke? Acta Neurology Scandinavia 1989; 126: 23-33. Clapham DE. TRP channels as cellular sensors. Nature 2003; 426: 517-24. Miller BA. The role of TRP channels in oxidative stress- induced cell death. J Membr Biol 2006:209: 31-41. Sun L, Yau HY, Wong WY, Li RA, Huang Y, Yao X. Role of TRPM2 inH(2)O(2)-induced cell apoptosis in endothelial cells. PLoS One 2012; 7: 43186. Lange I, Yamamoto S, Partida-Sanchez S, Mori Y, Fleig A, Penner R. TRPM2 functions as a lysosomal Ca2+ release channel in beta cells. Sci Signal 2009; 2: 23. Nilius B, Owsianik G, Voets T, Peters JA. Transient Receptor Potential cation channels in disease. Physiol Rev 2007; 87: 165-217. Alexhander SP, Mathie A, Peters JA. Guide to Reseptors and Ion Channels, 1st edition. Br J Pharmacol 2004; 141: 1-126. Hara Y, Wakamori M, Ishii M, et al. LTRPC2 Ca2+- permeable channel activated by changes in redox status confers susceptibility to cell death. Mol Cell 2002; 9: 163-73. Lange I, Yamamoto S, Partida-Sanchez S, Mori Y, Fleig A, Penner R. TRPM2 functions as a lysosomal Ca2+-release channel in beta cells. Sci Signal 2009; 19: 23. Taniyama Y, Griendling KK. Reactive oxygen species in the vasculature: molecular and cellular mechanisms. Hypertension 2003; 42: 1075-81. 27. 28. 29. 30. 31. 32. Kuloğlu T, Kocaman N. Enalapril Uygulanan Diyabetik Sıçan Böbrek Dokularında TRPM2 Kanal İmmunreaktivitelerinin Belirlenmesi FÜ Sağ Bil Tıp Derg 2013; 27: 27-32. Toklu HZ, Kwon OS, Sakarya Y. The effects of enalapril and losartan on mechanical ventilation-induced sympathoadrenal activation and oxidative stress in rats. J Surg Res 2014; doi: 10.1016. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997; 389: 816-24. Akiba Y, Kato S, Katsube K, et al. Transient receptor potential vanilloid subfamily 1 expressed in pancreatic islet beta cells modulates insülin secretion in rats. Biochem Biophys Res Commun 2004; 321: 219-25. Nazıroğlu M, Ciğ B, Ozgül C. Neuroprotection induced by N- acetylcysteine against cytosolic glutathione depletion-induced Ca2+ influx in dorsal root ganglion neurons of mice: role of TRPV1 channels. Neuroscience 2013; 242: 151-60. Ueda K, Tsuji F, Hirata T, Takaoka M, Matsumura Y. Preventive effect of TRPV1 agonists capsaicin and resiniferatoxin on ischemia/reperfusion-induced renal injury in rats. J Cardiovasc Pharmacol 2008; 51: 513-20. 33. 34. 35. 36. 37. Tsagogiorgas C, Wedel J, Hottenrot, et al. N-octanoyl- dopamine is an agonist at the capsaicin receptor TRPV1 and mitigates is che- mia-induced acute kidney injury in rat. PLoS One 2012;7: e43525. Yang D, Luo Z, Ma S, et al. Activation of TRPV1 by dietary capsaicin improves endothelium-dependent vasorelaxation and prevents hypertension. Cell Metab 2010; 12: 130-41. Zhang LL, Yan Liu D. Ma LQ, et al. Activation of transient receptor potential vanilloid type-1 channel prevents adipogenesis and obesity. Circ Res 2007; 100: 1063-70. Ma L, Zhong J, Zhao Z, et al. Activation of TRPV1 reduces vascular lipid accumulation and attenuates atherosclerosis. Cardiovasc Res 2011; 92: 504-13. Lee J, Saloman JL, Weiland G, Auh QS, Chung MK, Ro JY. Functional interactions between NMDA receptors and TRPV1 in trigeminal sensory neurons mediate mechanical hyperalgesia in the rat masseter muscle. Pain 2012; 153: 1514- 24.
Fırat Tıp Dergisi-Cover
  • ISSN: 1300-9818
  • Başlangıç: 2015
  • Yayıncı: Fırat Üniversitesi Tıp Fakültesi
Sayıdaki Diğer Makaleler

Primer Derinin B-Hücreli Lenfoması: Diffüz Büyük B-Hücreli Lenfoma, Bacak Tipi

Ayşe MURAT, İbrahim Hanifi ÖZERCAN

Çoklu Travma Hastasında Gelişen Yağ Embolisi Sendromu

İLKER ÖNGÜÇ AYCAN, Hüseyin TURGUT, Abdulmenap GÜZEL, Erdal DOĞAN, Gönül KAVAK ÖLMEZ

Apandisitlerin Perfore Olmasında Hekimlerin Rolü

MEHMET SARAÇ, ÜNAL BAKAL, Turgay TARTAR, AHMET KAZEZ

Primary Cutaneous B-Cell Lymphoma: Diffuse Large B-cell Lymphoma, Leg Type

Ayşe MURAT, İbrahim Hanifi ÖZERCAN

Okul Çağı Çocuklarında Şeker Tüketiminin Beden Kütle İndeksine Etkisinin Değerlendirilmesi

EDA KÖKSAL, MERVE ŞEYDA KARAÇİL ERMUMCU

Kadınların İsteğe Bağlı Sezaryen Konusundaki Görüşleri

BÜLENT ÇAKMAK, Seher ARSLAN, MEHMET CAN NACAR

Deneysel Diyabetik Sıçan Böbrek Dokusunda TRPV1 ve TRPM2 Kanallarına Losartanın Etkileri

GÖKHAN ARTAŞ, Tuncay KULOĞLU

Klinik Deneyimimiz ile İzole Pulmoner Metastaz Varlığında Cerrahinin Yeri

Aslı Gül AKGÜL, Seymur Salih MEHMETOĞLU, Devrim ÇABUK, Serkan ÖZBAY, HÜSEYİN FATİH SEZER, Şerife Tuğba LİMAN, SALİH TOPÇU

Malatya İl Merkezinde Çalışan Aile Hekimleri ile Aile Sağlığı Elemanlarının, Aile Hekimliği Uygulaması Hakkındaki Görüşleri, İş Doyumu Düzeyleri ve Etkileyen Faktörler

Çiğdem TEKİN, ÇİĞDEM BOZKIR, Yasemin SAZAK, Ali ÖZER

Kutis Marmorata Telenjektatika Konjenita: Bir Olgu Sunumu

ÖMER FARUK ELMAS, Okan KIZILYEL, Mahmut Sami METİN, Ali KARAKUZU, Şule BİLİCİ