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Comparison of Protective Effects of Melatonin and Amifostine on Radiation-Induced Renal Oxidative Stress in Rats

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In this study, we aimed to compare the protective effects of melatonin and amifostine on radiation-induced oxidative stress. Fifty female Wistar rats (3-4 months old, weighing 200±25 g) were divided into five groups (with ten rats each) and treated as follows: control (Cont), radiotherapy alone (RT), radiotherapy + amifostine (RT+AMI), radiotherapy + melatonin (RT+MEL), radiotherapy + amifostine + melatonin (RT+AMI+MEL). Rats were irradiated individually with a single dose of 8 Gy and amifostine (200 mg/kg) and melatonin (10 mg/kg) was administered to rats 30 minutes before irradiation. At the end of this follow-up period (72 hours) the rats were sacrificed. Spectrophotometric Analysis has been performed to kidney tissue samples. As a result of statistical comparison between groups after RT, total antioxidant capacity (TAC) decreased, total oxidant status (TOS) and oxidative stress index (OSI) increased, although the statistically significant change was only for OSI (p = 0.030). Addition of AMI or MEL to RT increased TAC and OSI significantly (p = 0.000), but there was no additive effect for TAC and OSI when both drugs were given together (p = 1.000, p = 0.172, respectively). In terms of TOS, statistically significant increasing was only for AMI (p = 0.000). There was protective effect when both drugs were given together against on Radiation-Induced Renal Oxidative Stress.


melatonin; amifostine; radiation-induced renal oxidative stress; rats

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Aycicek, A., Erel, O., & Kocyigit, A. (2005). Increased oxidative stress in infants exposed to passive smoking. Eur J Pediatr, 164(12), 775-778.doi:10.1007/s00431-005-1720-1

Baldwin, W. S., & Barrett, J. C. (1998). Melatonin Attenuates Hydrogen Peroxide Toxicity in MCF7 Cells Only at Pharmacological Concentrations. Biochemical and Biophysical Research Communications, 250(3), 602-605. doi:https://doi.org/10.1006/bbrc.1998.9370

Blickenstaff, R. T., Brandstadter, S. M., Reddy, S., & Witt, R. (1994). Potential radioprotective agents. 1. Homologs of melatonin. J Pharm Sci, 83(2), 216-218.

Caloglu, M., Yurut-Caloglu, V., Durmus-Altun, G., Oz-Puyan, F., Ustun, F., Cosar-Alas, R., . . . Uzal, C. (2009). 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, 36(5-6), 523-530. doi:10.1111/j.1440-1681.2008.05103.x

Cosar, R., Yurut-Caloglu, V., Eskiocak, S., Ozen, A., Altaner, S., Ibis, K., . . . Kocak, Z. (2012). Radiation-induced chronic oxidative renal damage can be reduced by amifostine. Med Oncol, 29(2), 768-775. doi:10.1007/s12032-011-9870-7

El-Sokkary, G. H., Omar, H. M., Hassanein, A. F., Cuzzocrea, S., & Reiter,R. J. (2002). Melatonin reduces oxidative damage and increases survival of mice infected with Schistosoma mansoni. Free Radic Biol Med, 32(4), 319-332.

Erel, O. (2004). A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem, 37(2),112-119.

Erel, O. (2005). A new automated colorimetric method for measuring total oxidant status. Clin Biochem, 38(12), 1103-1111. doi:10.1016/j.clinbiochem. 2005.08.008

Flohe, L., Gunzler, W. A., & Schock, H. H. (1973). Glutathione peroxidase: a selenoenzyme. FEBS Lett, 32(1), 132-134.

Haghi-Aminjan, H., Farhood, B., Rahimifard, M., Didari, T., Baeeri, M., Hassani, S., .bdollahi, M. (2018). The protective role of melatonin in chemotherapy-induced nephrotoxicity: a review of non-clinical studies. Expert Opin Drug Metab Toxicol, 14(9), 937-950. doi:10.1080/17425255.2018.1513492

Hara, M., Iigo, M., Ohtani-Kaneko, R., Nakamura, N., Suzuki, T., Reiter, R. J., & Hirata, K. (1997). Administration of melatonin and related indoles prevents exercise-induced cellular oxidative changes in rats. Biol Signals, 6(2), 90-100.

Hensley, M. L., Hagerty, K. L., Kewalramani, T., Green, D. M., Meropol, N. J., Wasserman, T. H., . . . Schuchter, L. M. (2009). American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol, 27(1), 127-145. doi:10.1200/jco.2008.17.2627

Jacevic, V., Dragojevic-Simic, V., Tatomirovic, Z., Dobric, S., Bokonjic, D., Kovacevic, A., . . . Kuca, K. (2018). The Efficacy of Amifostine against Multiple-Dose Doxorubicin-Induced Toxicity in Rats. Int J Mol Sci, 19(8). doi:10.3390/ijms19082370

Kaldir, M., Cosar-Alas, R., Cermik, T. F., Yurut-Caloglu, V., Saynak, M., Altaner, S., . . . Uzal, C. (2008). Amifostine use in radiation-induced kidney damage. Preclinical evaluation with scintigraphic and histopathologic parameters. Strahlenther Onkol, 184(7), 370-375.doi:10.1007/s00066-008-1777-7

Kirkman, H. N., Rolfo, M., Ferraris, A. M., & Gaetani, G. F. (1999). Mechanisms of protection of catalase by NADPH. Kinetics and stoichiometry. J Biol Chem, 274(20), 13908-13914.

Kotler, M., Rodriguez, C., Sainz, R. M., Antolin, I., & Menendez-Pelaez, A. (1998). Melatonin increases gene expression for antioxidant enzymes in rat brain cortex. J Pineal Res, 24(2), 83-89.

Kregel, K. C., & Zhang, H. J. (2007). An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations. Am J Physiol Regul Integr Comp Physiol, 292(1), R18-36. doi:10.1152/ajpregu.00327.2006

Levi, M., Knol, J. A., Ensminger, W. D., DeRemer, S. J., Dou, C., Lunte, S. M., . . . Smith, D. E. (2002). Regional pharmacokinetics of amifostine in anesthetized dogs: role of the liver, gastrointestinal tract, lungs, and kidneys. Drug Metab Dispos, 30(12), 1425-1430.

Lowry, O. H., Rosebrough, N. J., Farr, A. L., & Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. J Biol Chem, 193(1), 265-275.

Ozbek, E. (2012). Induction of oxidative stress in kidney. Int J Nephrol, 2012, 465897. doi:10.1155/2012/465897

Ozturk, E., Balat, O., Acilmis, Y. G., Ozcan, C., Pence, S., & Erel, O. (2011). Measurement of the placental total antioxidant status in preeclamptic women using a novel automated method. J Obstet Gynaecol Res, 37(4), 337-342. doi:10.1111/j.1447-0756.2010.01346.x

Rolleman, E. J., Forrer, F., Bernard, B., Bijster, M., Vermeij, M., Valkema, R., . . . de Jong, M. (2007). Amifostine protects rat kidneys during peptide receptor radionuclide therapy with [177Lu-DOTA0,Tyr3]octreotate. Eur J Nucl Med Mol Imaging, 34(5), 763-771. doi:10.1007/s00259-006-0291-3

Saada Helen, N., & Azab Khaled, S. (2001). Role of lycopene in recovery of radiation induced injury to mammalian cellular organelles. Pharmazie, 56(3), 239-241.

Sener, G., Jahovic, N., Tosun, O., Atasoy, B. M., & Yegen, B. C. (2003). Melatonin ameliorates ionizing radiation-induced oxidative organ damage in rats. Life Sci, 74(5), 563-572.

Spitz, D. R., Azzam, E. I., Li, J. J., & Gius, D. (2004). Metabolic oxidation/reduction reactions and cellular responses to ionizing radiation: a unifying concept in stress response biology. Cancer Metastasis Rev, 23(3-4), 311-322. doi:10.1023/B:CANC.0000031769.14728.bc

Stankiewicz, A., & Skrzydlewska, E. (2003). Protection against cyclophosphamide-induced renal oxidative stress by amifostine: the role of antioxidative mechanisms. Toxicol Mech Methods, 13(4), 301-308.doi:10.1080/713857191

Sun, J., Chen, Y., Li, M., & Ge, Z. (1998). Role of antioxidant enzymes on ionizing radiation resistance. Free Radic Biol Med, 24(4), 586-593.

Vijayalaxmi, Reiter, R. J., & Meltz, M. L. (1995). Melatonin protects human blood lymphocytes from radiation-induced chromosome damage. Mutat Res, 346(1), 23-31.

Vijayalaxmi, Reiter, R. J., Sewerynek, E., Poeggeler, B., Leal, B. Z., & Meltz, M. L. (1995). Marked reduction of radiation-induced micronuclei in human blood lymphocytes pretreated with melatonin. Radiat Res, 143(1), 102-106.

Zelko, I. N., Mariani, T. J., & Folz, R. J. (2002). Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radic Biol Med, 33(3), 337-349.


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