Comparison of the effects of melatonin and genistein on radiation‑induced nephrotoxicity: Results of an experimental study

Canyilmaz,Emine; Uslu,Gonca Hanedan; Bahat,Zumrut; Kandaz,Mustafa; Mungan,Sevdegul; Haciislamoglu,Emel; Mentese,Ahmet; Yoney,Adnan

doi:10.3892/br.2015.547

Comparison of the effects of melatonin and genistein on radiation‑induced nephrotoxicity: Results of an experimental study

Authors:
- Emine Canyilmaz
- Gonca Hanedan Uslu
- Zumrut Bahat
- Mustafa Kandaz
- Sevdegul Mungan
- Emel Haciislamoglu
- Ahmet Mentese
- Adnan Yoney
View Affiliations

Affiliations: Department of Radiation Oncology, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, Turkey, Department of Radiation Oncology, Faculty of Medicine, Kanuni Research and Education Hospital, 60080 Trabzon, Turkey, Department of Medical Pathology, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, Turkey, Department of Medical Biochemistry, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, Turkey
Published online on: November 24, 2015 https://doi.org/10.3892/br.2015.547
Pages: 45-50

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to compare the effects of melatonin and genistein on radiation‑induced nephrotoxicity (RIN). A total of 70 Swiss Albino mice were divided into 7 groups. Five control groups were defined, which were sham irradiation (C, G1), radiation therapy only (RT, G2), melatonin (M, G3), genistein (G, G4) and polyethylene glycol‑400 (G5), respectively. The co‑treatment groups were the RT plus melatonin (RT+M, G6) and RT plus genistein (RT+G, G7) groups. Irradiation was applied using a cobalt‑60 teletherapy machine (80‑cm fixed source‑to‑surface distance, 2.5‑cm depth). Melatonin was administered (100 mg/kg, intraperitoneal injection) 30 min before the single dose of irradiation, whereas genistein was administered (200 mg/kg, subcutaneous injection) 1 day before the single dose of irradiation. All the mice were sacrificed 6 months after irradiation. As an end point, the extent of renal tubular atrophy for each mouse was quantified with image analysis of histological sections of the kidney. Tissue malondialdehyde (MDA) levels were also measured in each animal. In the histopathological examination of the mouse kidneys, there was a statistically significant reduction (P<0.05) in the presence of tubular atrophy between the RT+M and RT+G groups and the RT group. There was a statistically significant increase in MDA levels in the irradiated versus sham groups (RT vs. C; P<0.05); however, MDA levels were significantly decreased by co‑treatment with melatonin or genistein vs. RT alone (RT+M and RT+G vs. RT; P<0.05). In conclusion, the present experimental study showed that melatonin and genistein supplementation prior to irradiation‑protected mice against RIN, which may have therapeutic implications for radiation‑induced injuries.

View Figures

View References

1	Robbins ME and Bonsib SM: Radiation nephropathy: A review. Scanning Microsc. 9:535–560. 1995.PubMed/NCBI
2	Bolling T, Schuck A, Rube C, Hesselmann S, Pape H, Dieckmann K, Pollinger B, Kortmann RD, Speiser-Held I, Meyer FM, et al: Therapy-associated late effects after irradiation of malignant diseases in childhood and adolescence. Feasibility analyses of a prospective multicenter register study. Strahlenther Onkol. 182:443–449. 2006.(In German). PubMed/NCBI
3	Cohen EP and Robbins ME: Radiation nephropathy. Semin Nephrol. 23:486–499. 2003. View Article : Google Scholar : PubMed/NCBI
4	Vijayalaxmi Meltz ML, Reiter RJ, Herman TS and Kumar KS: Melatonin and protection from whole-body irradiation: Survival studies in mice. Mutat Res. 425:21–27. 1999. View Article : Google Scholar : PubMed/NCBI
5	El-Missiry MA: Prophylactic effect of melatonin on lead-induced inhibition of heme biosynthesis and deterioration of antioxidant system in male rats. J Biochem Mol Toxicol. 14:57–62. 2000. View Article : Google Scholar : PubMed/NCBI
6	El-Missiry MA and El-Aziz Abd AF: Influence of melatonin on proliferation and antioxidant system in Ehrlich ascites carcinoma cells. Cancer Lett. 151:119–125. 2000. View Article : Google Scholar : PubMed/NCBI
7	Shirazi A, Ghobadi G and Ghazi-Khansari M: A radiobiological review on melatonin: A novel radioprotector. J Radiat Res (Tokyo). 48:263–272. 2007. View Article : Google Scholar
8	Vijayalaxmi Reiter RJ, Tan DX, Herman TS and Thomas CR Jr: Melatonin as a radioprotective agent: A review. Int J Radiat Oncol Biol Phys. 59:639–653. 2004. View Article : Google Scholar : PubMed/NCBI
9	Reiter RJ, Tan DX, Cabrera J, D'Arpa D, Sainz RM, Mayo JC and Ramos S: The oxidant/antioxidant network: Role of melatonin. Biol Signals Recept. 8:56–63. 1999. View Article : Google Scholar : PubMed/NCBI
10	Othman AI, El-Missiry MA and Amer MA: The protective action of melatonin on indomethacin-induced gastric and testicular oxidative stress in rats. Redox Rep. 6:173–177. 2001. View Article : Google Scholar : PubMed/NCBI
11	Othman AI, al Sharawy S and el-Missiry MA: Role of melatonin in ameliorating lead induced haematotoxicity. Pharmacol Res. 50:301–307. 2004. View Article : Google Scholar : PubMed/NCBI
12	Reiter RJ, Tan DX, Manchester LC and Qi W: Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: A review of the evidence. Cell Biochem Biophys. 34:237–256. 2001. View Article : Google Scholar : PubMed/NCBI
13	Reiter RJ, Tan DX, Gitto E, Sainz RM, Mayo JC, Leon J, Manchester LC, Vijayalaxmi Kilic E and Kilic U: Pharmacological utility of melatonin in reducing oxidative cellular and molecular damage. Pol J Pharmacol. 56:159–170. 2004.PubMed/NCBI
14	Kaya H, Delibas N, Serteser M, Ulukaya E and Ozkaya O: The effect of melatonin on lipid peroxidation during radiotherapy in female rats. Strahlenther Onkol. 175:285–288. 1999. View Article : Google Scholar : PubMed/NCBI
15	Reiter RJ, Tan DX, Osuna C and Gitto E: Actions of melatonin in the reduction of oxidative stress. A review. J Biomed Sci. 7:444–458. 2000. View Article : Google Scholar : PubMed/NCBI
16	Kruk I, Aboul-Enein HY, Michalska T, Lichszteld K and Kladna A: Scavenging of reactive oxygen species by the plant phenols genistein and oleuropein. Luminescence. 20:81–89. 2005. View Article : Google Scholar : PubMed/NCBI
17	Weiss JF and Landauer MR: Radioprotection by antioxidants. Ann N Y Acad Sci. 899:44–60. 2000. View Article : Google Scholar : PubMed/NCBI
18	Liang HW, Qiu SF, Shen J, Sun LN, Wang JY, Bruce IC and Xia Q: Genistein attenuates oxidative stress and neuronal damage following transient global cerebral ischemia in rat hippocampus. Neurosci Lett. 438:116–120. 2008. View Article : Google Scholar : PubMed/NCBI
19	Kang JL, Lee HW, Lee HS, Pack IS, Castranova V and Koh Y: Time course for inhibition of lipopolysaccharide-induced lung injury by genistein: Relationship to alteration in nuclear factor-kappaB activity and inflammatory agents. Crit Care Med. 31:517–524. 2003. View Article : Google Scholar : PubMed/NCBI
20	Landauer MR, Srinivasan V and Seed TM: Genistein treatment protects mice from ionizing radiation injury. J Appl Toxicol. 23:379–385. 2003. View Article : Google Scholar : PubMed/NCBI
21	Davis TA, Mungunsukh O, Zins S, Day RM and Landauer MR: Genistein induces radioprotection by hematopoietic stem cell quiescence. Int J Radiat Biol. 84:713–726. 2008. View Article : Google Scholar : PubMed/NCBI
22	Hillman GG, Wang Y, Kucuk O, Che M, Doerge DR, Yudelev M, Joiner MC, Marples B, Forman JD and Sarkar FH: Genistein potentiates inhibition of tumor growth by radiation in a prostate cancer orthotopic model. Mol Cancer Ther. 3:1271–1279. 2004.PubMed/NCBI
23	Raffoul JJ, Wang Y, Kucuk O, Forman JD, Sarkar FH and Hillman GG: Genistein inhibits radiation-induced activation of NF-kappaB in prostate cancer cells promoting apoptosis and G2/M cell cycle arrest. BMC Cancer. 6:1072006. View Article : Google Scholar : PubMed/NCBI
24	Valko M, Rhodes CJ, Moncol J, Izakovic M and Mazur M: Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact. 160:1–40. 2006. View Article : Google Scholar : PubMed/NCBI
25	Riley PA: Free radicals in biology: Oxidative stress and the effects of ionizing radiation. Int J Radiat Biol. 65:27–33. 1994. View Article : Google Scholar : PubMed/NCBI
26	Kleinman WA and Richie JP Jr: Status of glutathione and other thiols and disulfides in human plasma. Biochem Pharmacol. 60:19–29. 2000. View Article : Google Scholar : PubMed/NCBI
27	Karbownik M and Reiter RJ: Antioxidative effects of melatonin in protection against cellular damage caused by ionizing radiation. Proc Soc Exp Biol Med. 225:9–22. 2000. View Article : Google Scholar : PubMed/NCBI
28	Undeger U, Giray B, Zorlu AF, Oge K and Bacaran N: Protective effects of melatonin on the ionizing radiation induced DNA damage in the rat brain. Exp Toxicol Pathol. 55:379–384. 2004. View Article : Google Scholar : PubMed/NCBI
29	Taysi S, Koc M, Buyukokuroglu ME, Altinkaynak K and Sahin YN: Melatonin reduces lipid peroxidation and nitric oxide during irradiation-induced oxidative injury in the rat liver. J Pineal Res. 34:173–177. 2003. View Article : Google Scholar : PubMed/NCBI
30	Tahamtan R, Shabestani Monfared A, Tahamtani Y, Tavassoli A, Akmali M, Mosleh-Shirazi MA, Naghizadeh MM, Ghasemi D, Keshavarz M and Haddadi GH: Radioprotective effect of melatonin on radiation-induced lung injury and lipid peroxidation in rats. Cell J. 17:111–120. 2015.PubMed/NCBI
31	Kaldir M, Cosar-Alas R, Cermik TF, Yurut-Caloglu V, Saynak M, Altaner S, Caloglu M, Kocak Z, Tokatli F, Ture M, et al: Amifostine use in radiation-induced kidney damage. Preclinical evaluation with scintigraphic and histopathologic parameters. Strahlenther Onkol. 184:370–375. 2008. View Article : Google Scholar : PubMed/NCBI
32	Cosar R, Yurut-Caloglu V, Eskiocak S, Ozen A, Altaner S, Ibis K, Turan N, Denizli B, Uzal C, Saynak M, et al: Radiation-induced chronic oxidative renal damage can be reduced by amifostine. Med Oncol. 29:768–775. 2012. View Article : Google Scholar : PubMed/NCBI
33	Anwar MM and Moustafa MA: The effect of melatonin on eye lens of rats exposed to ultraviolet radiation. Comp Biochem Physiol C Toxicol Pharmacol. 129:57–63. 2001. View Article : Google Scholar : PubMed/NCBI
34	Gibbs FP and Vriend J: The half-life of melatonin elimination from rat plasma. Endocrinology. 109:1796–1798. 1981. View Article : Google Scholar : PubMed/NCBI
35	Wetterberg L, Eriksson O, Friberg Y and Vangbo B: A simplified radioimmunoassay for melatonin and its application to biological fluids. Preliminary observations on the half-life of plasma melatonin in man. Clin Chim Acta. 86:169–177. 1978. View Article : Google Scholar : PubMed/NCBI
36	Mihara M and Uchiyama M: Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem. 86:271–278. 1978. View Article : Google Scholar : PubMed/NCBI
37	Kucuktulu E, Yavuz AA, Cobanoglu U, Yenilmez E, Eminagaoglu S, Karahan C, Topbas M and Kucuktulu U: Protective effect of melatonin against radiation induced nephrotoxicity in rats. Asian Pac J Cancer Prev. 13:4101–4105. 2012. View Article : Google Scholar : PubMed/NCBI
38	Cassady JR: Clinical radiation nephropathy. Int J Radiat Oncol Biol Phys. 31:1249–1256. 1995. View Article : Google Scholar : PubMed/NCBI
39	Kim TH, Freeman CR and Webster JH: The significance of unilateral radiation nephropathy. Int J Radiat Oncol Biol Phys. 6:1567–1571. 1980. View Article : Google Scholar : PubMed/NCBI
40	Prager W and Merkelbach K: Long-term sequelae in the kidneys following abdominal irradiation of advanced malignant ovarian tumors. Radiobiol Radiother (Berl). 27:341–345. 1986.(In German). PubMed/NCBI
41	Kim BC, Shon BS, Ryoo YW, Kim SP and Lee KS: Melatonin reduces X-ray irradiation-induced oxidative damages in cultured human skin fibroblasts. J Dermatol Sci. 26:194–200. 2001. View Article : Google Scholar : PubMed/NCBI
42	Vijayalaxmi Reiter RJ, Herman TS and Meltz ML: Melatonin and radioprotection from genetic damage: In vivo/in vitro studies with human volunteers. Mutat Res. 371:221–228. 1996. View Article : Google Scholar : PubMed/NCBI
43	Vijayalaxmi Reiter RJ, Herman TS and Meltz ML: Melatonin reduces gamma radiation-induced primary DNA damage in human blood lymphocytes. Mutat Res. 397:203–208. 1998. View Article : Google Scholar : PubMed/NCBI
44	Sharma S, Haldar C, Chaube SK, Laxmi T and Singh SS: Long-term melatonin administration attenuates low-LET gamma-radiation-induced lymphatic tissue injury during the reproductively active and inactive phases of Indian palm squirrels (Funambulus pennanti). Br J Radiol. 83:137–151. 2010. View Article : Google Scholar : PubMed/NCBI
45	Sharma S, Haldar C and Chaube SK: Effect of exogenous melatonin on X-ray induced cellular toxicity in lymphatic tissue of Indian tropical male squirrel, Funambulus pennanti. Int J Radiat Biol. 84:363–374. 2008. View Article : Google Scholar : PubMed/NCBI
46	Sener G, Jahovic N, Tosun O, Atasoy BM and Yeğen BC: Melatonin ameliorates ionizing radiation-induced oxidative organ damage in rats. Life Sci. 74:563–572. 2003. View Article : Google Scholar : PubMed/NCBI
47	Karslioglu I, Ertekin MV, Taysi S, Koçer I, Sezen O, Gepdiremen A, Koç M and Bakan N: Radioprotective effects of melatonin on radiation-induced cataract. J Radiat Res (Tokyo). 46:277–282. 2005. View Article : Google Scholar
48	Haddadi G, Shirazi A, Sepehrizadeh Z, Mahdavi SR and Haddadi M: Radioprotective effect of melatonin on the cervical spinal cord in irradiated rats. Cell J. 14:246–253. 2013.PubMed/NCBI
49	Erol FS, Topsakal C, Ozveren MF, Kaplan M, Ilhan N, Ozercan IH and Yildiz OG: Protective effects of melatonin and vitamin E in brain damage due to gamma radiation: An experimental study. Neurosurg Rev. 27:65–69. 2004. View Article : Google Scholar : PubMed/NCBI
50	Weiss JF and Landauer MR: Protection against ionizing radiation by antioxidant nutrients and phytochemicals. Toxicology. 189:1–20. 2003. View Article : Google Scholar : PubMed/NCBI
51	Wei H, Zhang X, Wang Y and Lebwohl M: Inhibition of ultraviolet light-induced oxidative events in the skin and internal organs of hairless mice by isoflavone genistein. Cancer Lett. 185:21–29. 2002. View Article : Google Scholar : PubMed/NCBI
52	Shimoi K, Masuda S, Furugori M, Esaki S and Kinae N: Radioprotective effect of antioxidative flavonoids in gamma-ray irradiated mice. Carcinogenesis. 15:2669–2672. 1994. View Article : Google Scholar : PubMed/NCBI
53	Anné PR and Curran WJ Jr: A phase II trial of subcutaneous amifostine and radiation therapy in patients with head and neck cancer. Semin Radiat Oncol. 12(Suppl 1): 18–19. 2002. View Article : Google Scholar : PubMed/NCBI
54	White DC: The histopathologic basis for functional decrements in late radiation injury in diverse organs. Cancer. 37(Suppl 2): 1126–1143. 1976. View Article : Google Scholar : PubMed/NCBI
55	Williams MV and Denekamp J: Sequential functional testing of radiation-induced renal damage in the mouse. Radiat Res. 94:305–317. 1983. View Article : Google Scholar : PubMed/NCBI
56	Kim JS, Heo K, Yi JM, Gong EJ, Yang K, Moon C and Kim SH: Genistein mitigates radiation-induced testicular injury. Phytother Res. 26:1119–1125. 2012. View Article : Google Scholar : PubMed/NCBI