İyonizer Radyasyonun Neden Olduğu Akut Renal Hasara Karşı Melatonin ve Amifostinin Koruyucu Etkilerinin Karşılaştırılması

Yıl 2013, Cilt: 1 Sayı: 2, 67 - 70, 12.07.2016

Alaattin Özen Ebru Taştekin Suat Cakina Sule Parlar Nukhet Kurkcu Necdet Sut Cem Uzal

Öz

Bu çalışmanın amacı, erken dönemde iyonizer radyasyonun neden olduğu akut böbrek hasarı üzerine melatonin ve amifostinin koruyucu etkisinin histopatolojik olarak karşılaştırılmasıdır. 50 dişi albino rat kontrol, yalnız radyoterapi, radyoterapi+amifostin, radyoterapi+melatonin ve radyoterapi+amifostin+melatonin olmak üzere beş gruba ayrıldı. İntraperitoneal amifostin (200 mg/kg) ve intraperitoneal melatonin (10 mg/kg) radyoterapiden 30 dakika önce uygulandı. Tek tek ratların tüm vücutlarına 8 Gy eksternal radyopterapi uygulandı. Takip süresinin sonunda her bir hayvan için segmental veya total nekroz gibi böbrek korteksi glomerul hasarı sayılarak hasarlı glomerul yüzdesi tespit edildi. Amifostin, melatonin ve amifostin+melatonin'in koruyucu etkisi istatistiksel olarak gösterilmekle birlikte melatonin lehine bir avantaj tespit edilmiştir (p = 0.005). Melatonin’e amifostin eklenmesinin tek basına melatonine göre üstünlüğü olmamasına karşın (p = 0.243) amifostine melatonin eklenmesinin tek basına amifostine göre istatistiksel üstünlüğü gösterilmiştir (p = 0.003). Sonuç olarak melatonin’in iyonizer radyasyonun neden olduğu akut böbrek hasarı üzerine koruyucu etkisi amifostin’den histopatolojik olarak daha iyidir.

Anahtar Kelimeler

Amifostin, melatonin, akut renal hasar, iyonizer radyasyon

Comparison of Protective Effect of Melatonin and Amifostine on Acute Renal Damage Caused by Ionizing Radiation

Öz

The aim of this study is to compare histopathologically the protective effect of melatonin and amifostine on radiation induced renal damage. 50 female albino rats were divided into five groups: control, radiotherapy alone, radiotherapy+amifostine, radiotherapy+melatonin, radiotherapy+amifostine+melatonin. Intraperitoneal amifostine (200 mg/kg) and intraperitoneal melatonin (10 mg/kg) was administered to 30 minutes before irradiation. Rats were irradiated with a single dose of 8 Gy on whole body. At the end of the follow-up period, percentage of damaged glomeruli was determined by counting damaged glomeruli of kidney cortex as segmental or total necrosis for each animal. The protective effect of each agent has been shown, and there is an advantage in favor of melatonin (p = 0.005). Although there is not an advantage of adding amifostine to melatonin (p = 0.243), there is statistically significant better protective effect in amifostine+melatonin group when compared with amifostine alone (p = 0.003). The protective effect of melatonin on radiation induced acute renal toxicity is histopathologically better than amifostine.

Anahtar Kelimeler

Amifostine, melatonin, acute renal damage, ionizing radiation

Kaynakça

• Cassady JR. Clinical radiation nephropathy. Int J Radiat Oncol Biol Phys 1995; 31: 1249-1256.
• van der Vijgh WJ, Peters GJ. Protection of normal tissues from the cytotoxic effects of chemotherapy and radiation by amifostine (WR-2721): preclinical aspects. Eur J Cancer 1995; 21(Suppl 11): 2-7.
• Cohen EP, Robbins ME. Radiation nephropathy. Semin Nephrol 2003; 23: 486-499.
• Rosen S, Swerdlow MA, Muehrcke RC, Pirani CL. Radiation Nephritis; Light and Electron Microscopic Observations. Am J Clin Pathol 1964; 41: 487-502.
• Cogan MG, Arieff AI. Radiation nephritis and intravascular coagulation. Clin Nephrol 1978; 10: 74-78.
• Jennette JC, Ordóñez NG. Radiation nephritis causing nephrotic syndrome. Urology 1983; 22: 631-634.
• Donaldson SS, Moskowitz PS, Evans JW, Fajardo LF. Protection from radiation nephropathy by WR-2721. Radiat Res 1984; 97: 414-423.
• Uzal C, Durmus-Altun G, Caloglu M, Ergülen A, Altaner S, Yigitbasi NO. The protective effect of amifostine on radiationinduced acute pulmonary toxicity: detection by (99m)Tc-DTPA transalveolar clearances. Int J Radiat Oncol Biol Phys 2004; 60: 564-569.
• Kaldir M, Cosar-Alas R, Cermik TF, et al. Amifostine use in radiation-induced kidney damage. Preclinical evaluation with scintigraphic and histopathologic parameters. Strahlenther Onkol 2008; 184: 370-375.
• Rodriguez C, Mayo JC, Sainz RM, et al. Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res 2004; 36: 1-9.
• Vijayalaxmi, Reiter RJ, Tan DX, Herman TS, Thomas CR Jr. Melatonin as a radioprotective agent: a review. Int J Radiat Oncol Biol Phys 2004; 59: 639-653.
• Cosar R, Yurut-Caloglu V, Eskiocak S, et al. Radiationinduced chronic oxidative renal damage can be reduced by amifostine. Med Oncol. 2012 Jun;29(2):768-75
• Sener G, Jahovic N, Tosun O, Atasoy BM, Yeğen BC. Melatonin ameliorates ionizing radiationinduced oxidative organ damage in rats. Life Sci 2003; 74: 563-572.
• Krochak R, Baker DG. Radiation nephritis. Clinical manifestations and pathophysiological mechanisms. Urology 1986; 27: 389-393.
• Robbins M, Stephens L, Johnston D, et al. A morphometric analysis of glomerular and tubular alterations following fast neutron irradiation of the pig and monkey kidney. Int J Rad Biol Phys 1998; 41: 1149-1156.
• Mostofi FK, Pani KC, Ericsson J. Effects of irradiaton on canine kidney. Am J Pathol 1964; 44: 707-725.
• Madrazo A, Suzuki Y, Churg J. Radiation nephritis. II. Chronic changes after high doses of radiation. Am J Pathol 1970; 61: 37-56.
• Madrazo A, Suzuki Y, Churg J. Radiation nephritis: acute changes following high dose of radiation.Am J Pathol 1969; 54: 507-527.
• Phillips TL, Ross G. A quantitative technique for measuring renal damage after irradiation. Radiology 1973; 109: 457-462.
• Madrazo A, Schwarz G, Churg J. Radiation nephritis: a review. J Urol 1975; 114: 822-827.
• Moss RW. Do antioxidants interfere with radiation therapy for cancer? Integr Cancer Ther 2007; 6: 281-292.
• Karbownik M, Reiter RJ, Qi W, et al. Protective effects of melatonin against oxidation of guanine bases in DNA and decreased microsomal membrane fluidity in rat liver induced by whole body ionizing radiation. Mol Cell Biochem 2000; 211: 137-144.
• Caloglu M, Caloglu VY, Yalta T, Yalcin O, Uzal C. The histopathological comparison of L-carnitine with amifostine for protective efficacy on radiation-induced acute small intestinal toxicity. J Cancer Res Ther 2012; 8: 260-265.
• Caloglu M, Yurut-Caloglu V, Durmus-Altun G, et al. Histopathological and scintigraphic comparisons of the protective effects of L-carnitine andamifostine against radiationinduced late renal toxicity in rats. Clin Exp Pharmacol Physiol 2009; 36: 523-530.
• Topkan E, Tufan H, Yavuz AA, et al. Comparison of the protective effects of melatonin and amifostine on radiation-induced epiphyseal injury. Int J Radiat Biol 2008; 84: 796-802.