Abstract
In the present world, X-rays have been regarded as one of the most efficient tools in medicine, industry and research. On the contrary, extensive human exposure to these rays is responsible for causing detrimental effects on physiological system. The aim of the present study was to investigate the role of zinc (Zn), if any, in mitigating the adverse effects induced by fractionated X-irradiation on rat brain. Female Sprague-Dawley rats weighing 170–200 g were divided into four different groups viz.: (a) normal control, (b) X-irradiated (21Gy), (c) zinc treated (227 mg/L in drinking water) and (d) X-irradiated + zinc treated. The skulls of animals belonging to groups (b) and (d) were exposed to X-rays in 30 fractions. Each fraction delivered a radiation dose of 70 rads, and rats were exposed to two fractions every day for 15 days, consecutively. X-ray treatment resulted in significant alterations in the neurobehavior, neurotransmitter levels and neuro-histoarchitecture of rats, whereas zinc co-treatment with X-rays resulted in significant improvement in these parameters. X-ray exposure also caused a significant increase in the levels of lipid peroxidation as well as activities of catalase and superoxide dismutase, which however were decreased upon simultaneous Zn treatment. On the contrary, X-ray treatment down-regulated the glutathione system, which were found to be up-regulated by zinc co-treatment. Further, protein expressions of p53 and NF-ҚB were found to be significantly elevated after X-irradiation, which were reversed following Zn supplementation. Hence, Zn seems to be an effective agent in mitigating the detrimental effects caused by exposure to X-rays.
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Canale S, Balleyguier C, Dromain C (2013) Breast cancer imaging. Rev Prat 63:1378–1383
Insull EA, Hart RH, Sloan BH, Ben-Simon GJ, McNab AA (2013) Use of x-ray film implant for the repair of orbital fractures. Ophthal Plast Reconstr Surg 29:393–405
Manda K, Ueno M, Anzai K (2007) AFMK, a melatonin metabolite, attenuates X-ray-induced oxidative damage to DNA, proteins and lipids in mice. J Pineal Res 42:386–393
Caceres LG, Aon Bertolino L, Saraceno GE, Zorrilla Zubilete MA, Uran SL, Capani F, Guelman LR (2010) Hippocampal-related memory deficits and histological damage induced by neonatal ionizing radiation exposure. Role of oxidative status. Brain Res 1312:67–78
Kang KA, Zhang R, Chae S, Lee SJ, Kim J, Kim J, Jeong J, Lee J, Shin T, Lee NH, Hyun JW (2010) Phloroglucinol (1,3,5-trihydroxybenzene) protects against ionizing radiation-induced cell damage through inhibition of oxidative stress in vitro and in vivo. Chem Biol Interact 185:215–226
Hasan SS, Kushawa AK (1991) The effect of low doses of x-rays on the biochemical processes in the brain and on urinary metabolites in fasted rats. Radiobiologiia 31:326–332
Di CX, Yang LN, Zhang H, An LZ, Zhang X, Ma XF, Sun C, Wang XH, Yang R, Wu ZH, Si J (2013) Effects of carbon-ion beam or X-ray irradiation on anti-apoptosis ΔNp73 expression in HeLa cells. Gene 515:208–213
Sun AM, Li CG, Han YQ, Liu QL, Xia Q, Yuan YW (2013) X-ray irradiation promotes apoptosis of hippocampal neurons through up-regulation of Cdk5 and p25. Cancer Cell Int 13:47
Nagler R, Marmary Y, Golan E, Chevion M (1998) Novel protection strategy against X-ray-induced damage to salivary glands. Radiat Res 149:271–276
Polytarchou C, Kardamakis D, Katsoris P, Papadimitriou E (2006) Antioxidants modify the effect of X rays on blood vessels. Anticancer Res 26:3043–3047
Claus EB, Calvocoressi L, Bondy ML, Schildkraut JM, Wiemels JL, Wrensch M (2012) Dental x-rays and risk of meningioma. Cancer 118:4530–4537
Akkus O, Belaney RM, Das P (2005) Free radical scavenging alleviates the biomechanical impairment of gamma radiation sterilized bone tissue. J Orthop Res 23:838–845
Shin HS, Yang WJ, Choi EM (2013) The preventive effect of Se-methylselenocysteine on γ-radiation-induced oxidative stress in rat lungs. J Trace Elem Med Biol 27:154–159
Shirazi A, Mihandoost E, Ghobadi G, Mohseni M, Ghazi-Khansari M (2013) Evaluation of radio-protective effect of melatonin on whole body irradiation induced liver tissue damage. Cell J 14:292–297
Balentova S, Hajtmanova E, Trylcova R, Adamkov M, Lehotsky J (2014) Ionizing radiation induced long-term alterations in the adult rat rostral migratory stream. Acta Histochem 116:265–271
Boström M, Kalm M, Karlsson N, Hellström Erkenstam N, Blomgren K (2013) Irradiation to the young mouse brain caused long-term, progressive depletion of neurogenesis but did not disrupt the neurovascular niche. J Cereb Blood Flow Metab 33:935–943
Roughton K, Boström M, Kalm M, Blomgren K (2013) Irradiation to the young mouse brain impaired white matter growth more in females than in males. Cell Death Dis 4:e897
Prasad AS (2009) Impact of the discovery of human zinc deficiency on health. J Am Coll Nutr 28:257–265
Maret W (2013) Zinc and human disease. Met Ions Life Sci 13:389–414
MacDonald RS (2000) The role of zinc in growth and cell proliferation. J Nutr 130:1500S–1508S
Stefanidou M, Maravelias C, Dona A, Spiliopoulou C (2006) Zinc: a multipurpose trace element. Arch Toxicol 80:1–9
Levenson CW, Morris D (2011) Zinc and neurogenesis: making new neurons from development to adulthood. Adv Nutr 2:96–100
Gower-Winter SD, Levenson CW (2012) Zinc in the central nervous system: from molecules to behavior. Biofactors 38:186–193
Takeda A, Nakamura M, Fujii H, Tamano H (2013) Synaptic Zn(2+) homeostasis and its significance. Metallomics 5:417–423
Song Y, Xue Y, Liu X, Wang P, Liu L (2008) Effects of acute exposure to aluminum on blood-brain barrier and the protection of zinc. Neurosci Lett 445:42–46
Pavlica S, Gebhardt R (2010) Comparison of uptake and neuroprotective potential of seven zinc-salts. Neurochem Int 56:84–93
Szewczyk B, Poleszak E, Sowa-Kućma M, Siwek M, Dudek D, Ryszewska-Pokraśniewicz B et al (2008) Antidepressant activity of zinc and magnesium in view of the current hypotheses of antidepressant action. Pharmacol Rep 60:588–589
Miao X, Sun W, Fu Y, Miao L, Cai L (2013) Zinc homeostasis in the metabolic syndrome and diabetes. Front Med 7:31–52
Singla N, Dhawan DK (2015) Modulation of (14) C-labeled glucose metabolism by zinc during aluminium induced neurodegeneration. J Neurosci Res 93:1434–1441
Singla N, Dhawan DK (2013) Zinc, a neuroprotective agent against aluminum-induced oxidative DNA injury. Mol Neurobiol 48:1–12
Cox RH Jr, Perhach JL Jr (1973) A sensitive, rapid and simple method for the stimultaneous spectrophotofluorometric determinations of norepinephrine, dopamine, 5-hydroxytryptamine and 5-hydroxy-indoleacetic acid in discrete areas of brain. J Neurochem 20:1777–1780
Ellman GL, Lourtney KD, Andres VJ (1961) A new and rapid colorimetric determination of acetylcholiesterase activity. Biochem Pharmacol 7:88–95
Wills ED (1966) Mechanism of lipid peroxide formation in animal tissues. Biochem J 99:667–676
Kono Y (1978) Generation of superoxide radical during auto oxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophy 186:189–195
Luck H (1971) Catalase. In: Bergmeyer HU (ed) Methods of enzymatic analysis. Academic, New York, pp 885–893
Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70
Zahler WL, Cleland WW (1968) A specific and sensitive assay for disulfides. J Biol Chem 243:716–719
Wendel A (1980) Glutathione peroxidases. In: Jakoby WB (ed) Enzymatic basis of detoxification. Academic, New York, pp 333–353
Carlberg I, Mannervik B (1985) Glutathione reductase. Methods Enzymol 113:484–490
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Follin-phenol reagent. J Biol Chem 193:265–275
Towbin H, Staehelin T, Gordon J (1992) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Biotechnology 24:145–149
Lanzenberger RR, Mitterhauser M, Spindelegger C et al (2007) Reduced serotonin-1A receptor binding in social anxiety disorder. Biol Psychiatry 61:1081–1089
Miyachi Y, Kasai H, Ohyama H, Yamada T (1994) Changes of aggressive behavior and brain serotonin turnover after very low-dose X-irradiation of mice. Neurosci Lett 175:92–94
Caceres LG, Cid MP, Uran SL, Zorrilla Zubilete MA, Salvatierra NA, Guelman LR (2013) Pharmacological alterations that could underlie radiation-induced changes in associative memory and anxiety. Pharmacol Biochem Behav 111:37–43
Soares FA, Dalla Corte CL, Andrade ER, Marina R, González P, Barrio JP (2014) Purple grape juice as a protector against acute x-irradiation induced alterations on mobility, anxiety, and feeding behaviour in mice. Nutr Hosp 29:812–821
Russo AJ (2011) Decreased zinc and increased copper in individuals with anxiety. Nutr Metab Insights 4:1–5
Matias CM, Matos NC, Arif M, Dionisio JC, Quinta-Ferreira ME (2006) Effect of the zinc chelator N,N,N',N'-tetrakis (2-pyridylmethyl)ethylenediamine (TPEN) on hippocampal mossy fiber calcium signals and on synaptic transmission. Biol Res 39:521–530
Takeda A, Ando M, Kanno S, Oku N (2009) Unique response of zinc in the hippocampus to behavioral stress and attenuation of subsequent mossy fiber long-term potentiation. Neurotoxicology 30:712–717
Takeda A, Tamano H, Kan F, Itoh H, Oku N (2007) Anxiety-like behavior of young rats after 2-week zinc deprivation. Behav Brain Res 177:1–6
Yi ZX, Zhang W (2014) Effect of cerebral X-ray irradiation on learning and memory function in young SD rats. Zhejiang Da Xue Xue Bao Yi Xue Ban 43:535–540
Özyurt H, Özden AS, Çevik Ö, Özgen Z, Cadirci S, Elmas MA, Ercan F, Şener G, Gören MZ (2014) Investigation into the role of the cholinergic system in radiation-induced damage in the rat liver and ileum. J Radiat Res 55:866–875
Momosaki S, Sun XZ, Takai N, Hosoi R, Inoue O, Takahashi S (2002) Changes in histological construction and decrease in 3H-QNB binding in the rat brain after prenatal X-irradiation. J Radiat Res 43:277–282
Corniola RS, Tassabehji NM, Hare J, Sharma G, Levenson CW (2008) Zinc deficiency impairs neuronal precursor cell proliferation and induces apoptosis via p53-mediated mechanisms. Brain Res 1237:52–61
Sindreu C, Palmiter RD, Storm DR (2011) Zinc transporter ZnT-3 regulates presynaptic Erk1/2 signaling and hippocampus-dependent memory. Proc Natl Acad Sci U S A 108:3366–3370
Pan E, Zhang XA, Huang Z, Krezel A, Zhao M, Tinberg CE, Lippard SJ, McNamara JO (2011) Vesicular zinc promotes presynaptic and inhibits postsynaptic long-term potentiation of mossy fiber-CA3 synapse. Neuron 71:1116–1126
Joshi D, Mittal DK, Shukla S, Srivastav AK (2012) Therapeutic potential of N acetyl cysteine with antioxidants (Zn and Se) supplementation againstdimethylmercury toxicity in male albino rats. Exp Toxicol Pathol 64:103–108
Cho CH, Luk CT, Ogle CW (1991) The membrane-stabilizing action of zinc carnosine (Z-103) in stress-induced gastric ulceration in rats. Life Sci 49:189–194
Dopico AM, Zieher LM, Mayo J, Altschüller N, López JJ, Jaim-Etcheverry G (1989) Long-term changes in noradrenaline (NA) and dopamine (DA) contents of rat cerebellum following neonatal X-irradiation. Neurochem Int 15:97–105
Megha K, Deshmukh PS, Ravi AK, Tripathi AK, Abegaonkar MP, Banerjee BD (2015) Effect of low-intensity microwave radiation on monoamine neurotransmitters and their key regulating enzymes in rat brain. Cell Biochem Biophys 73:93–100
Lepping P, Huber M (2010) Role of zinc in the pathogenesis of attention-deficit hyperactivity disorder: implications for research and treatment. CNS Drugs 24:721–728
Bicer M, Gunay M, Baltaci AK, Uney K, Mogulkoc R, Akil M (2012) Effect of zinc supplementation on lipid peroxidation and lactate levels in rats with diabetes induced by streptozotocin and subjected to acute swimming exercise. Bratisl Lek Listy 113:199–205
Yalinkilic O, Enginar H (2008) Effect of X-radiation on lipid peroxidation and antioxidant systems in rats treated with saponin-containing compounds. Photochem Photobiol 84:236–242
Kalpana KB, Devipriya N, Thayalan K, Menon VP (2010) Protection against X-ray radiation-induced cellular damage of human peripheral blood lymphocytes by an aminothiazole derivative of dendrodoine. Chem Biol Interact 186:267–274
Rogalska J, Brzóska MM, Roszczenko A, Moniuszko-Jakoniuk J (2009) Enhanced zinc consumption prevents cadmium-induced alterations in lipid metabolism in male rats. Chem Biol Interact 177:142–152
Kumar SD, Vijaya M, Samy RP, Dheen ST, Ren M, Watt F, Kang YJ, Bay BH, Tay SS (2012) Zinc supplementation prevents cardiomyocyte apoptosis and congenital heart defects in embryos of diabetic mice. Free Radic Biol Med 53:1595–1606
Sidhu P, Garg ML, Dhawan DK (2004) Protective effects of zinc on oxidative stress enzymes in liver of protein deficient rats. Nutr Hosp 19:341–347
Singla N, Dhawan DK (2014) Zinc modulates aluminium-induced oxidative stress and cellular injury in rat brain. Metallomics 6:1941–1950
Zhou R, Si J, Zhang H, Wang Z, Li J, Zhou X, Gan L, Liu Y (2014) The effects of x-ray radiation on the eye development of zebrafish. Hum Exp Toxicol 33:1040–1050
Zheng J, Zhang Y, Xu W, Luo Y, Hao J, Shen XL, Yang X, Li X, Huang K (2013) Zinc protects HepG2 cells against the oxidative damage and DNA damage induced by ochratoxin a. Toxicol Appl Pharmacol 268:123–131
Singh S, Das Roy L, Giri S (2013) Curcumin protects metronidazole and X-ray induced cytotoxicity and oxidative stress in male germ cells in mice. Prague Med Rep 114:92–102
Neculai AM, Neculai D, Griesinger C, Vorholt JA, Becker S (2005) A dynamic zinc redox switch. J Biol Chem 280:2826–2830
Piatek K, Hartwig A, Bal W (2009) Physiological levels of glutathione enhance Zn (II) binding by a Cys4 zinc finger. Biochem Biophys Res Commun 389:265–268
Pace NJ, Weerapana E (2014) Zinc-binding cysteines: diverse functions and structural motifs. Biomolecules 4:419–434
Van den Berg R, Haenen GR, van den Berg H, Bast A (2001) Transcription factor NF-kappa B as a potential biomarker for oxidative stress. Br J Nutr 86:S121–S127
Uzzo RG, Crispen PL, Golovine K, Makhov P, Horwitz EM, Kolenko VM (2006) Diverse effects of zinc on NF-kappaB and AP-1 transcription factors: implications for prostate cancer progression. Carcinogenesis 27:1980–1990
Caceres LG, Aon Bertolino L, Saraceno GE, Zorrilla Zubilete MA, Uran SL, Capani F, Guelman LR (2010) Hippocampal-related memory deficits and histological damage induced by neonatal ionizing radiation exposure. Role of oxidative status Brain Res 1312:67–78
Authors’ Contributions
PS, NS, and DKD have designed this study as well as drafted this manuscript. All the authors have critically reviewed the content of this manuscript. PS and NS have performed various experiments and did analysis of data.
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We are grateful to University Grants Commission (UGC) (UGC-34-294/2008 SR), New Delhi, India.
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Sharma, P., Singla, N. & Dhawan, D.K. Evidence of Zinc in Affording Protection Against X-Ray-Induced Brain Injury in Rats. Biol Trace Elem Res 179, 247–258 (2017). https://doi.org/10.1007/s12011-017-0976-4
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DOI: https://doi.org/10.1007/s12011-017-0976-4