The Ionizing Radiation Effect on Liver and Kidney Tissue

Öz

Radiation-induced liver and kidney toxicity are among the major complications of radiation applications used in cancer treatment. Radiation damage that occurs in tissues and/or organs depends on the radiation dose recei-ved. In this study, it was aimed to evaluate the possible toxic effects of ionizing radiation (IR) given in different doses on rat liver and kidney tissue. Investigation the possible effects of different doses of ionized radiation (IR) on liver and kidney tissues. In this study, 40 female Wistar albino rats were randomly divided into 4 groups. The groups were deter-mined as the control group, 1 Gy radiation group, 5 Gy radiation group and 10 Gy radiation group. Radiation applicati-ons were performed as a single dose of total body irradiation using gamma rays. Liver and kidney tissues of the groups were evaluated histopathologically through Hematoxylin-Eosin (H&E), Masson trichrome and Periodic acid Schiff (PAS) staining. Furthermore, the number of apoptotic cells was determined by caspase-3 immunostaining. When liver tissues treated with IR were examined histologically, various damaged cellwere observed in the irradiated liver tissues, especi-ally vascular and interstitial hemorrhage areas, and also the degree of damage was directly proportional with the radia-tion dose. Compared to the control group, the most prominent fibrosis was observed in the group treated with 10 Gy radiation. Furthermore, glycogen content depletion of hepatocytes was seen in 5 Gy and 10 Gy groups. The IR applied caused changes and cellular damage in the renal tubules and interstitial tissue. Especially in the 5 Gy and 10 Gy IR applied groups, the amount of collagen fibers increased and proximal tubule epithelial cells were found to have thicke-ning of the epithelial basement membranes with marked loss of microvilli. The caspase-3 + cell count showed that IR have an apoptosis-enhancing effect on both liver and kidney tissues. As a result, the study findings revealed that the tissue damage and apoptotic cell number in the liver and kidney are dependent on the dose administered in the IR.

Anahtar Kelimeler

• Apoptosis
• ionizing radiation
• kidney
• liver

İyonize Radyasyonun Karaciğer ve Böbrek Dokusu Üzerine Etkisi

Öz

Kanser tedavisinde kullanılan radyasyon uygulamalarının önemli komplikasyonları arasında radyasyona bağlı karaciğer ve böbrek toksisitesi bulunur. Doku ve/veya organlarda şekillenen radyasyon hasarı, alınan radyasyon dozu-na bağlıdır. Bu çalışma ile farklı dozlarda verilen iyonize radyasyonun (IR) sıçan karaciğer ve böbrek dokusu üzerine olası toksik etkilerinin değerlendirilmesi amaçlandı. Çalışmada, 40 adet dişi Wistar albino cinsi sıçan rastgele 4 gruba ayrıldı. Gruplar; kontrol grubu, 1Gy radyasyon grubu, 5Gy radyasyon grubu ve 10Gy radyasyon grubu şeklinde belir-lendi. Radyasyon uygulamaları gama ışını kullanılarak tek doz total vücut ışınlaması şeklinde yapıldı. Gruplara ait kara-ciğer ve böbrek dokuları Hematoksilen-Eozin (H&E), Masson trikrom ve Periyodik asit Schiff (PAS) boyama ile histopa-tolojik olarak değerlendirildi. Ayrıca, kaspaz-3 immünboyama ile apopitotik hücre sayısı belirlendi. IR uygulanan karaci-ğer dokuları histolojik olarak incelendiğinde, radyasyon uygulanan karaciğer dokularında başta vasküler ve interstisyel hemoraji alanları olmak üzere çeşitli hücresel hasarlar gözlenmiş olup hasar dereceleri radyasyon dozu ile doğru oran-tılıydı. Kontrol grubu ile kıyaslandığında en belirgin fibrozisin 10 Gy radyasyon uygulanan grupta olduğu gözlendi. Ayrı-ca, 5 Gy ve 10 Gy gruplarında hepatositlerin glikojen içeriğinde tükenme olduğu görüldü. Uygulanan IR, böbrek tübülle-rinde ve interstisyel dokuda değişikliklere ve hücresel hasara neden oldu. Özellikle 5 Gy ve 10 Gy IR uygulanan grup-larda kollajen liflerin miktarının arttığı ve proksimal tübül epitel hücrelerinde belirgin mikrovillus kaybı ile epitel bazal membranlarında kalınlaşma olduğu görüldü. Kaspaz-3 + hücre sayısı IR’nin hem karaciğer hem de böbrek dokuları üzerinde apopitozu arttırıcı etkiye sahip olduğunu gösterdi. Sonuç olarak, çalışma bulguları karaciğer ve böbrekte olu-şan doku hasarının ve apopitotik hücre sayısının IR’da uygulanan doza bağlı olduğunu ortaya koymuştur.

Anahtar Kelimeler

• Apopitoz
• böbrek
• iyonize radyasyon
• karaciğer

Kaynakça

1. Benson R, Madan R, Kilambi R, Chander S. Radia-tion induced liver disease: A clinical update. J Egypt Natl Canc Inst 2016; 28(1): 7-11.
2. Caloglu M, Yurut-Caloglu V, Durmus-Altun G, Oz-Puyan F, Ustun F, Cosar-Alas R, Saynak M, Par-lar S, Turan FN, Uzal C. Histopathological and scintigraphic comparisons of the protective effects of L-carnitine and amifostine against radiation-induced late renal toxicity in rats. Clin Exp Pharmacol Physiol 2009; 36(5-6): 523-30.
3. Cheema AK, Mehta KY, Rajagopal MU, Wise SY, Fatanmi OO, Singh VK. Metabolomic studies of tissue injury in nonhuman primates exposed to gamma-radiation. Int J Mol Sci 2019; 20(13): 3360.
4. Cohen EP, Robbins ME. Radiation nephropathy. Semin Nephrol 2003; 23(5): 486-99.
5. Duport P, Jiang H, Shilnikova NS, Krewski D, Zielins-ki JM. Database of radiogenic cancer in experi-mental animals exposed to low doses of ionizing radiation. J Toxicol Environ Health B Crit Rev 2012; 15(3): 186-209.
6. Fuchs-Tarlovsky V. Role of antioxidants in cancer therapy. Nutri2013;29(1); 15-21.
7. Han N-K, Jung MG, Jeong YJ, Son Y, Han SC, Park S, Lim Y-B, Lee Y-J, Kim S-H, Park SC, Lee H-J. Plasma fibrinogen-like 1 as a potential biomarker for radiation-ınduced liver ınjury. Cells 2019; 8(9): 1042.
8. Hwang JM, Chan DC, Chang TM, Tsao TY, Tsou SS, Lu RH, Tsai LM. Effects of oral arginine and gluta-mine on radiation-induced injury in the rat. J Surg Res 2003; 109(2): 149-54.

9. Inomata T, Itoh S, Kariya S, Mesaki K, Nishioka A, Ogawa Y, Yoshida S, Sonobe H, Ohtsuki Y. Late pathologic changes in guinea pig kidneys irradia-ted with conventional fractionation and hyperfrac-tionation. Int J Radiat Oncol Biol Phys 1999; 44(1): 171-7.
10. Ismail AF, Zaher NH, El-Hossary EM, El-Gazzar MG. Modulatory effects of new curcumin analogues on gamma-irradiation-induced nephrotoxicity in rats. Chem Biol Interact 2016; 260: 141-53.
11. Karahan S, Çavuşoğlu K, Atmaca HT, Yalçın E. Albi-no farelerde iyonlaştırıcı radyasyonun hepatosit morfolojisi ve prolifere hücre çekirdek antijeni (PCNA) ekspresyonu üzerindeki etkileri. Erciyes Üniv Vet Fak Derg 2008; 5(2): 61-6.
12. Karbownik M, Reiter RJ. Antioxidative effects of me-latonin in protection against cellular damage cau-sed by ionizing radiation. Proc Soc Exp Biol Med 2000; 225(1): 9-22.
13. Kim J, Jung Y. Radiation-induced liver disease: cur-rent understanding and future perspectives. Exp Mol Med 2017; 49(7): e359.
14. Kucuktulu E. Protective effect of melatonine against radiation induced nephrotoxicity in rats. Asian Pac J Cancer Prev 2012; 13(8): 4101-5.
15. Mansour SZ, El-Marakby SM, Moawed FSM. Amelio-rative effects of rutin on hepatic encephalopathy-induced by thioacetamide or gamma irradiation. J Photochem Photobiol B 2017; 172: 20-7.
16. Martinon F, Tschopp J. Inflammatory caspases: Lin-king an intracellular innate immune system to autoinflammatory diseases. Cell 2004; 117(5): 561-74.
17. Moulder JE, Cohen EP. Radiation-induced multi-organ involvement and failure: The contribution of radiation effects on the renal system. Br J Radiol 2005; 27(1): 82-8.
18. Nakajima T, Wang B, Ono T, Uehara Y, Nakamura S, Ichinohe K, Braga-Tanaka I, Tanaka S, Tanaka K, Nenoi M. Differences in sustained alterations in protein expression between livers of mice expo-sed to high-dose-rate and low-dose-rate radiation. J Radiat Res 2017; 58(4): 421-9.
19. Park HS, You GE, Yang KH, Kim JY, An S, Song JY, Lee S-J, Lim Y-K, Nam SY. Role of AKT and ERK pathways in controlling sensitivity to ionizing radi-ation and adaptive response induced by low-dose radiation in human immune cells. Eur J Cell Biol 2015; 94(12): 653-60.
20. Okunieff P, Chen, Maguire D, Huser AK. Molecular markers of radiation-related normal tissue toxicity. Cancer Metastasis Rev 2008; 27(3): 363-74.
21. Özgüner F, Mollaoglu H. Manyetik alanın organizma üzerindeki biyolojik etkileri. Med J SDU 2006; 13(1): 38-41.
22. Prasanna PG, Stone HB, Wong RS, Capala J, Bern-hard EJ, Vikram B, Coleman CN. Normal tissue protection for improving radiotherapy: Where are the Gaps? Transl Cancer Res 2012; 1(1): 35- 48.
23. Salem AM, Mohammaden TF, Ali MA, Mohamed EA, Hassan HF. Ellagic and ferulic acids alleviate gamma radiation and aluminium chloride-induced oxidative damage. Life Sci 2016; 160: 2-11.
24. Sagar SM. Should patients take or avoid antioxidant supplements during anticancer therapy? An evi-dence-based review. Curr Oncol 2005; 12(2): 44-54.
25. Sharma R, Sharma J. Modification of gamma ray induced changes in the mouse hepatocytes by Centella asiatica extract: İn vivo studies. Phytother Res 2005; 19(7): 605-11.
26. Shinomiya N. New concepts in radiation-induced apoptosis:premitotic apoptosis and postmitotic apoptosis. J Cell Mol Med 2001; 5(3): 240-53.
27. Taysi S, Koc M, Büyükokuroğlu ME, Altinkaynak K, Sahin YN. Melatonin reduces lipid peroxidation and nitric oxide during irradiation-induced oxidati-ve injury in the rat liver. J Pineal Res 2003; 34(3): 173-7.
28. Verheij M, Bartelink H. Radiation-induced apoptosis. Cell Tissue Res 2000; 301: 133-42.
29. Wang M-J, Ling W-W, Wang H, Meng L-W, Cai H, Peng B. Non-invasive evaluation of liver stiffness after splenectomy in rabbits with CCl4-induced liver fibrosis. World J Gastroenterol 2016; 22(46): 10166-79.
30. Yay A, Goktepe O, Bahadir A, Ozdamar S, Oktem IS, Coruh A, Baran M. Assessment of markers expressed in human hair follicles according to different skin regions. Adv Clin Exp Med 2018; 27(7): 929-39.