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Article

Hepatic Nrf2 expression is altered by quercetin supplementation in X‑irradiated rats

  • Authors:
    • Raquel Marina
    • Paquita González
    • M. Carmen Ferreras
    • Serafín Costilla
    • Juan‑Pablo Barrio
  • View Affiliations / Copyright

    Affiliations: Universidad Autónoma de Chile, Santiago de Chile 7500566, Chile, Department of Biomedical Sciences, University of León, León 24071, Spain, Department of Animal Health, University of León, León 24071, Spain, Department of Medicine, University of Oviedo, Oviedo 33006, Spain
  • Pages: 539-546
    |
    Published online on: October 22, 2014
       https://doi.org/10.3892/mmr.2014.2741
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Abstract

Whole‑body irradiation has been associated with liver function alterations. Ionizing radiation exposure increases oxidative stress and antioxidants can activate transcription of antioxidant target genes. In the present study, modifications of the liver antioxidant system were evaluated at 7 and 30 days following sub‑lethal whole‑body X‑irradiation in male Wistar rats, which were intragastrically supplemented with quercetin or control solvent for 4 days prior to and 6 days following irradiation. Animal groups were as follows: CS, control, solvent‑supplemented; CQ, control, quercetin‑supplemented; RS, irradiated, solvent‑supplemented; and RQ, irradiated, quercetin‑supplemented. After 7 days, liver tissue from RS animals demonstrated marked hydropic panlobular degeneration with Mallory bodies in ballooning hepatocytes. These changes were mostly reversed in RQ rats. Lipid peroxidation in addition to copper/zinc superoxide dismutase (Cu/Zn‑SOD), nuclear factor (erythroid‑derived 2)‑like 2 (Nrf2) and Kelch‑like ECH‑associated protein 1 (Keap1) protein expression levels were all increased by X‑irradiation, but significantly decreased by quercetin supplementation. Catalase (CAT) and NAD(P)H: quinone oxidoreductase 1 (NQO1) expression levels remained high in irradiated rats regardless of quercetin supplementation. After 30 days, the liver from RS animals had small portal infiltrates and diffuse cytoplasmic vacuolization, with reduced lipid peroxidation and reduced expression levels of CAT, NQO1, Nrf2 and Keap1, but consistently elevated Cu/Zn‑SOD expression. RQ animals indicated reduced expression levels of Nrf2 and Keap1 30 days after irradiation. The present study demonstrated a quercetin‑induced reduction of the oxidative stress‑associated increase in Nrf2 expression that may be useful for preventing cancer cell survival in response to ionizing radiation exposure.
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1 

Tanigawa S, Fujii M and Hou D: Action of Nrf2 and Keap1 in ARE-mediated NQO1 expression by quercetin. Free Rad Biol Med. 42:1690–1703. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Aleksunes LM and Manautou JE: Emerging role of Nrf2 in protecting against hepatic and gastrointestinal disease. Toxicol Pathol. 35:459–473. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Middleton EJ, Kandaswami C and Theoharides T: The effects of plants flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev. 52:673–751. 2000.PubMed/NCBI

4 

González-Gallego J, García-Mediavilla MV, Sánchez-Campos S and Tuñón MJ: Fruit polyphenols, immunity and inflammation. Br J Nutr. 104:S15–S27. 2010.PubMed/NCBI

5 

Hosseinimehr SJ: Trends in the development of radioprotective agents. Drug Discov Today. 12:794–805. 2007. View Article : Google Scholar

6 

Otsuka K, Koana T, Tauchi H and Sakai K: Activation of antioxidative enzymes induced by low-dose-rate whole-body gamma irradiation: adaptive response in terms of initial DNA damage. Radiat Res. 166:474–478. 2006. View Article : Google Scholar : PubMed/NCBI

7 

Okunieff P, Swarts S, Keng P, et al: Antioxidants reduce consequences of radiation exposure. Adv Exp Med Biol. 614:165–178. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Marnett LJ: Oxy radicals, lipid peroxidation and DNA damage. Toxicology. 181–182:219–222. 2002.PubMed/NCBI

9 

Wallace DC: The mitochondrial genome in human adaptive radiation and disease: on the road to therapeutics and performance enhancement. Gene. 354:169–180. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Nwokocha CR, Nwokocha M, Mounmbegna P, et al: Proteins and liver function changes in rats following cumulative total body irradiations. West Indian Med J. 61:773–777. 2012.PubMed/NCBI

11 

Citrin D, Cotrim AP, Hyodo F, et al: Radioprotectors and mitigators of radiation-induced normal tissue injury. Oncologist. 15:360–371. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Kawai Y, Saito S, Nishikawa T, et al: Different profiles of quercetin metabolites in rat plasma: comparison of two administration methods. Biosci Biotechnol Biochem. 73:517–523. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Willis ED: Evaluation of lipid peroxidation in lipids and biological membranes. Biochemical Toxicology: A Practical Approach. Snell KB and Mullock B: IRL Press; Oxford: pp. 407–420. 1987

14 

Jung JH, Kang JI and Kim HS: Effect of quercetin on impaired immune function in mice exposed to irradiation. Nutr Res Pract. 6:301–307. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Kanter M, Aktas C and Erboga M: Protective effects of quercetin against apoptosis and oxidative stress in streptozotocin-induced diabetic rat testis. Food Chem Toxicol. 50:719–25. 2012. View Article : Google Scholar

16 

Benkovic V, Knezevic AH, Dikic D, et al: Radioprotective effects of quercetin and ethanolic extract of propolis in gamma-irradiated mice. Arh Hig Rada Toksikol. 60:129–138. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Sezer A, Usta U, Kozak Z and Yagci MA: The effect of a flavonoid fractions diosmin + hesperidin on radiation-induced acute proctitis in a rat model. J Cancer Res Ther. 7:152–156. 2011. View Article : Google Scholar : PubMed/NCBI

18 

An JH, Kim J and Seong J: Redox signaling by ionizing radiation in mouse liver. Ann NY Acad Sci. 1030:86–94. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Cromheecke M, Konings AW, Szabo BG and Hoekstra HJ: Liver tissue tolerance for irradiation: experimental and clinical investigations. Hepatogastroenterology. 47:1732–4170. 2000.PubMed/NCBI

20 

Alati T, Van Cleef M, Strom SC and Jirtle RL: Radiation sensitivity of adult human parenchymal hepatocytes. Radiat Res. 115:152–160. 1988. View Article : Google Scholar : PubMed/NCBI

21 

Pei RJ, Danbara N, Tsujita-Kyutoku M, et al: Immunohistochemical profiles of Mallory body by a panel of anti-cytokeratin antibodies. Med Electron Microsc. 37:114–118. 2004.PubMed/NCBI

22 

Bhosle SM, Huilgol NG and Mishra KP: Enhancement of radiation-induced oxidative stress and cytotoxicity in tumor cells by ellagic acid. Clin Chim Acta. 359:89–100. 2005. View Article : Google Scholar : PubMed/NCBI

23 

Karran P: DNA double strand break repair in mammalian cells. Curr Opin Genetics Dev. 10:144–150. 2000. View Article : Google Scholar : PubMed/NCBI

24 

Andrade ER, Cruz IB, Andrade VV, et al: Evaluation of the potential protective effects of ad libitum black grape juice against liver oxidative damage in whole-body acute X-irradiated rats. Food Chem Toxicol. 49:1026–1032. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Meydan D, Gursel B, Bilgici B, Can B and Ozbek N: Protective effect of lycopene against radiation-induced hepatic toxicity in rats. J Int Med Res. 39:1239–1252. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Tsukimoto M, Tamaishi N, Homma T and Kojima S: Low-dose gamma-ray irradiation induced translocation of Nrf2 into nuclear in mouse macrophague RAW264.7. J Radiat Res. 51:349–353. 2010. View Article : Google Scholar : PubMed/NCBI

27 

McDonald JT, Kim K, Norris AJ, et al: Ionizing radiation activates the Nrf2 antioxidant response. Cancer Res. 70:8886–8895. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Liu Y, Zhang L, Zhang H, et al: Exogenous melatonin modulates apoptosis in the mouse brain induced by high-LET carbon ion irradiation. J Pineal Res. 52:47–56. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Jung KH, Hong SW, Zheng HM, Lee DH and Hong SS: Melatonin downregulates nuclear erythroid 2-related factor 2 and nuclear factor-kappaB during prevention of oxidative liver injury in a dimethylnitrosamine model. J Pineal Res. 47:173–183. 2009. View Article : Google Scholar

30 

Li W, Khor TO, Xu C, et al: Activation of Nrf2-antioxidant signaling attenuates NFkappaB-inflammatory response and elicits apoptosis. Biochem Pharmacol. 76:1485–1489. 2008. View Article : Google Scholar : PubMed/NCBI

31 

Lee OH, Jain AK, Papusha V and Jaiswal AK: An auto-regulatory loop between stress sensors INrf2 and Nrf2 controls their cellular abundance. J Biol Chem. 282:36412–36420. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Milani P, Gagliardi S, Cova E and Cereda C: SOD1 Transcriptional and Posttranscriptional Regulation and Its Potential Implications in ALS. Neurol Res Int. 2011:4584272011.PubMed/NCBI

33 

Park EY and Rho HM: The transcriptional activation of the human copper/zinc superoxide dismutase gene by 2,3,7,8-tetrachlorodibenzo-p-dioxin through two different regulator sites, the antioxidant responsive element and xenobiotic responsive element. Mol Cell Biochem. 240:47–55. 2002. View Article : Google Scholar

34 

Terakado N, Shintani S, Nakahara Y, et al: Expression of Cu/Zn-SOD, Mn-SOD and GST-pi in oral cancer treated with preoperative radiation therapy. Oncol Rep. 7:1113–1117. 2000.PubMed/NCBI

35 

Vucic V, Isenovic ER, Adzic M, Ruzdijic S and Radojcic MB: Effects of gamma-radiation on cell growth, cycle arrest, death, and superoxide dismutase expression by DU 145 human prostate cancer cells. Braz J Med Biol Res. 39:227–236. 2006. View Article : Google Scholar : PubMed/NCBI

36 

Boots AW, Bast A and Haenen GR: No role of DT-diaphorase (NQO1) in the protection against oxidized quercetin. FEBS Lett. 579:677–82. 2005. View Article : Google Scholar : PubMed/NCBI

37 

Orlowski RZ and Baldwin AS Jr: NF-kappaB as a therapeutic target in cancer. Trends Mol Med. 8:385–389. 2002. View Article : Google Scholar : PubMed/NCBI

38 

Bravard A, Luccioni C, Moustacchi E and Rigaud O: Contribution of antioxidant enzymes to the adaptative response to ionizing radiation of human lymphoblasts. Int J Radiat Biol. 75:639–645. 1999. View Article : Google Scholar : PubMed/NCBI

39 

Crespo I, Garcia-Mediavilla MV, Almar M, et al: Differential effects of dietary flavonoids on reactive oxygen and nitrogen species generation and changes in antioxidant enzyme expression induced by proinflammatory cytokines in Chang Liver cells. Food Chem Toxicol. 46:1555–1569. 2008. View Article : Google Scholar

40 

Kook D, Wolf AH, Yu AL, et al: The protective effect of quercetin against oxidative stress in the human RPE in vitro. Invest Ophthalmol Vis Sci. 49:1712–1720. 2008. View Article : Google Scholar : PubMed/NCBI

41 

Duthie G and Morrice P: Antioxidant capacity of flavonoids in hepatic microsomes is not reflected by antioxidant effects in vivo. Oxid Med Cell Longev. 2012:1651272012.PubMed/NCBI

42 

Nakamura Y, Ishimitsu S and Tonogai Y: Effects of quercetin and rutin on serum and hepatic lipid concentrations, fecal steroid excretion and serum antioxidant properties. J Health Sci. 46:229–240. 2000. View Article : Google Scholar

43 

Wang XJ, Sun Z, Villeneuve NF, et al: Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2. Carcinogenesis. 29:1235–1243. 2008. View Article : Google Scholar : PubMed/NCBI

44 

Lin C, Yu Y, Zhao HG, et al: Combination of quercetin with radiotherapy enhances tumor radiosensitivity in vitro and in vivo. Radiother Oncol. 104:395–400. 2012. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Marina R, González P, Ferreras MC, Costilla S and Barrio JP: Hepatic Nrf2 expression is altered by quercetin supplementation in X‑irradiated rats. Mol Med Rep 11: 539-546, 2015.
APA
Marina, R., González, P., Ferreras, M.C., Costilla, S., & Barrio, J. (2015). Hepatic Nrf2 expression is altered by quercetin supplementation in X‑irradiated rats. Molecular Medicine Reports, 11, 539-546. https://doi.org/10.3892/mmr.2014.2741
MLA
Marina, R., González, P., Ferreras, M. C., Costilla, S., Barrio, J."Hepatic Nrf2 expression is altered by quercetin supplementation in X‑irradiated rats". Molecular Medicine Reports 11.1 (2015): 539-546.
Chicago
Marina, R., González, P., Ferreras, M. C., Costilla, S., Barrio, J."Hepatic Nrf2 expression is altered by quercetin supplementation in X‑irradiated rats". Molecular Medicine Reports 11, no. 1 (2015): 539-546. https://doi.org/10.3892/mmr.2014.2741
Copy and paste a formatted citation
x
Spandidos Publications style
Marina R, González P, Ferreras MC, Costilla S and Barrio JP: Hepatic Nrf2 expression is altered by quercetin supplementation in X‑irradiated rats. Mol Med Rep 11: 539-546, 2015.
APA
Marina, R., González, P., Ferreras, M.C., Costilla, S., & Barrio, J. (2015). Hepatic Nrf2 expression is altered by quercetin supplementation in X‑irradiated rats. Molecular Medicine Reports, 11, 539-546. https://doi.org/10.3892/mmr.2014.2741
MLA
Marina, R., González, P., Ferreras, M. C., Costilla, S., Barrio, J."Hepatic Nrf2 expression is altered by quercetin supplementation in X‑irradiated rats". Molecular Medicine Reports 11.1 (2015): 539-546.
Chicago
Marina, R., González, P., Ferreras, M. C., Costilla, S., Barrio, J."Hepatic Nrf2 expression is altered by quercetin supplementation in X‑irradiated rats". Molecular Medicine Reports 11, no. 1 (2015): 539-546. https://doi.org/10.3892/mmr.2014.2741
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