Protective effects of genistein and melatonin on mouse liver injury induced by whole‑body ionising radiation

Hanedan Uslu,Gonca; Canyilmaz,Emine; Serdar,Lasif; Ersöz,Şafak

doi:10.3892/mco.2018.1790

Protective effects of genistein and melatonin on mouse liver injury induced by whole‑body ionising radiation

Authors:
- Gonca Hanedan Uslu
- Emine Canyilmaz
- Lasif Serdar
- Şafak Ersöz
View Affiliations

Affiliations: Department of Radiation Oncology, Health Sciences University Kanuni Training and Research Hospital, Trabzon 61250, Turkey, Department of Radiation Oncology, Faculty of Medicine, Karadeniz Technical University, Trabzon 61080, Turkey, Department of Medical Pathology, Faculty of Medicine, Karadeniz Technical University, Trabzon 61080, Turkey
Published online on: December 11, 2018 https://doi.org/10.3892/mco.2018.1790
Pages: 261-266

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 investigate the effectiveness of melatonin and genistein in preventing radiation therapy (RT)‑induced liver injury in mice. A total of 70 Swiss Albino male mice were divided into 7 equal groups (n=10/group) as follows: Melatonin (M group, G3), genistein (G group, G4), polyethylene glycol‑400 (P group, G5), RT only (RT group, G2) and sham irradiation (C group, G1). RT plus genistein (RT+G group, G7) and RT plus melatonin (RT+M group, G6) were the co‑treatment groups. Firstly, hepatic tissue damage was induced in mice via exposure to a single dose of 6‑Gy irradiation. RT was performed with a cobalt‑60 teletherapy machine (80 cm fixed source‑to‑surface distance, 2.5‑cm depth). Melatonin was processed (100 mg/kg, intraperitoneal) 30 min before and genistein was administered (200 mg/kg, SC) one day prior to the single dose of irradiation. Six months following irradiation, all mice were sacrificed. The degree of liver injury was measured using histological liver sections. Liver injury was significantly worse in the RT group than in the control group (C; RT vs. C; P<0.05); however, liver injury decreased following co‑treatment with melatonin or genistein vs. RT alone (RT+M and RT+G vs. RT; P<0.05). No difference was observed between the RT+M and RT+G groups (P>0.05). The present study revealed that melatonin and genistein administration prior to irradiation protects mice against liver injury, which may have therapeutic implications for RT‑induced injuries.

View Figures

View References

1	Rubin P, Johnston CJ, Williams JP, McDonald S and Finkelstein JN: A perpetual cascade of cytokines postirradiation leads to pulmonary fibrosis. Int J Radiat Oncol Biol Phys. 33:99–109. 1995. View Article : Google Scholar : PubMed/NCBI
2	Zheng H, Wang J, Koteliansky VE, Gotwals PJ and Hauer-Jensen M: Recombinant soluble transforming growth factor beta type II receptor ameliorates radiation enteropathy in mice. Gastroenterology. 119:1286–1296. 2000. View Article : Google Scholar : PubMed/NCBI
3	Fajardo LF: Pathology of radiation injury. New York: Masson Publishers; pp. 27–30. 1982
4	Reed GB Jr and CoxA J Jr: The human liver after radiation injury. A form of veno-occlusive disease. Am J Pathol. 48:597–611. 1966.PubMed/NCBI
5	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
6	Sies H: Oxidative stress: A concept in redox biology and medicine. Redox Biol. 4:180–183. 2015. View Article : Google Scholar : PubMed/NCBI
7	Varanda EA and Tavares DC: Radioprotection: Mechanisms and radioprotective agents including honeybee venom. J Venom Anim Toxins. 4:5–21. 1998. View Article : Google Scholar
8	Berbee M, Fu Q, Boerma M, Pathak R, Zhou D, Kumar KS and Hauer-Jensen M: Reduction of radiation-induced vascular nitrosative stress by the vitamin E analog gammatocotrienol: Evidence of a role for tetrahydrobiopterin. Int J Radiat Oncol Biol Phys. 79:884–891. 2011. View Article : Google Scholar : PubMed/NCBI
9	Knight DC and Eden JA: A review of the clinical effects of phytoestrogens. Obstet Gynecol. 87:897–904. 1996.PubMed/NCBI
10	Khan S, Adhikari JS, Rizvi MA and Chaudhury NK: Radioprotective potential of melatonin against ⁶⁰Co γ-ray-induced testicular injury in male C57BL/6 mice. J Biomed Sci. 22:612015. View Article : Google Scholar : PubMed/NCBI
11	Kaldir M, Cosar-Alas R, Cermik TF, Yurut-Caloglu V, Saynak M, Altaner S, Caloglu M, Kocak Z, Tokatli F, Türe 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
12	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
13	Anwar MM and Moustafa MA: The effect of melatonin on eye lens of mice exposed to ultraviolet radiation. Comp Biochem Physiol C Toxicol Pharmacol. 129:57–63. 2001. View Article : Google Scholar : PubMed/NCBI
14	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
15	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
16	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
17	Singh VK, Grace MB, Parekh VI, Whitnall MH and Landauer MR: Effects of genistein administration on cytokine induction in whole-body gamma irradiated mice. Int Immunopharmacol. 9:1401–1410. 2009. View Article : Google Scholar : PubMed/NCBI
18	Goodman ZD: Grading and staging systems for inflammation and fibrosis in chronic liver diseases. J Hepatol. 47:598–607. 2007. View Article : Google Scholar : PubMed/NCBI
19	Smith TA, Kirkpatrick DR, Smith S, Smith TK, Pearson T, Kailasam A, Herrmann KZ, Schubert J and Agrawal DK: Radioprotective agents to prevent cellular damage due to ionizing radiation. J Transl Med. 15:2322017. View Article : Google Scholar : PubMed/NCBI
20	Tan DX, Reiter RJ, Manchester LC, Yan MT, El-Sawi M, Sainz RM, Mayo JC, Kohen R, Allegra M and Hardeland R: Chemical and physical properties and potential mechanisms: Melatonin as a broad spectrum antioxidant and free radical scavenger. Curr Top Med Chem. 2:181–197. 2002. View Article : Google Scholar : PubMed/NCBI
21	Koc M, Taysi S, Buyukokuroglu ME and Bakan N: Melatonin protects rat liver against irradiation-induced oxidative injury. J Radiat Res. 44:211–215. 2003. View Article : Google Scholar : PubMed/NCBI
22	Taysi S, Koc M, Büyükokuroğlu ME, Altınkaynak K and Şahin 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
23	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
24	Vijayalaxmi, Reiter RJ and Meltz ML: Melatonin protects human blood lymphocytes from radiation-induced chromosome damage. Mutat Res. 346:23–31. 1995. View Article : Google Scholar : PubMed/NCBI
25	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
26	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
27	Sener G, Jahovic N, Tosun O, Atasoy BM and Yeğen BÇ: Melatonin ameliorates ionizing radiation-induced oxidative organ damage in rats. Life Sci. 74:563–572. 2003. View Article : Google Scholar : PubMed/NCBI
28	Kucuktulu E: 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
29	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. 46:277–282. 2005. View Article : Google Scholar : PubMed/NCBI
30	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
31	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
32	Vijayalaxmi, Meltz ML, Reiter RJ, Herman TS and Kumar S: Melatonin and protection from whole-body irradiation: Survival studies in mice. Mutat Res. 425:21–27. 1999. View Article : Google Scholar : PubMed/NCBI
33	Davis TA, Clarke TK, Mog SR and Landauer MR: Subcutaneous administration of genistein prior to lethal irradiation supports multilineage, hematopoietic progenitor cell recovery and survival. Int J Radiat Biol. 83:141–151. 2007. View Article : Google Scholar : PubMed/NCBI