Abstract
Due to numerous industrial applications, lead has caused widespread pollution in the environment; it seems that the central nervous system (CNS) is the main target for lead in the human body. Oxidative stress and programmed cell death in the CNS have been assumed as two mechanisms related to neurotoxicity of lead. Cerium oxide (CeO2) and yttrium oxide (Y2O3) nanoparticles have recently shown antioxidant effects, particularly when used together, through scavenging the amount of reactive oxygen species (ROS) required for cell apoptosis. We looked into the neuroprotective effects of the combinations of these nanoparticles against acute lead-induced neurotoxicity in rat hippocampus. We used five groups in this study: control, lead, CeO2 nanoparticles + lead, Y2O3 nanoparticles + lead, and CeO2 and Y2O3 nanoparticles + lead. Nanoparticles of CeO2 (1000 mg/kg) and Y2O3 (230 mg/kg) were administered intraperitoneally during 2 days prior to intraperitoneal injection of the lead (25 mg/kg for 3 days). At the end of the treatments, oxidative stress markers, antioxidant enzymes activity, and apoptosis indexes were investigated. The results demonstrated that pretreatments with CeO2 and/or Y2O3 nanoparticles recovered lead-caused oxidative stress markers (ROS, lipid peroxidation, and total thiol molecules) and apoptosis indexes (Bax/Bcl-2 and caspase-3 protein expression). Besides, these nanoparticles reduced the activities of lead-induced superoxide dismutase and catalase as well as the ADP/ATP ratio. Interestingly, the best recovery resulted from the compound of these nanoparticles. Based on these outcomes, it appears that this combination may potentially be beneficial for protection against lead-caused acute toxicity in the brain through improving the oxidative stress-mediated programmed cell death pathway.
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References
Wang J, Wu J, Zhang Z (2006) Oxidative stress in mouse brain exposed to lead. Ann Occup Hyg 50:405–409
Kermanian F, Mehdizadeh M, Nourmohammadi I (2010) Effects of vitamin C supplementation on lead-induced apoptosis in adult rat hippocampus. Neural Regener Res 5:364–367
Eren I, Naziroğlu M, Demirdaş A (2007) Protective effects of lamotrigine, aripiprazole and escitalopram on depression-induced oxidative stress in rat brain. Neurochem Res 32:1188–1195
Nazıroğlu M, Senol N, Ghazizadeh V, Yürüker V (2014) Neuroprotection induced by N-acetylcysteine and selenium against traumatic brain injury-induced apoptosis and calcium entry in hippocampus of rat. Cell Mol Neurobiol 34:895–903
Dilek M, Naziroğlu M, Baha Oral H et al (2010) Melatonin modulates hippocampus NMDA receptors, blood and brain oxidative stress levels in ovariectomized rats. J Membr Biol 233:135–142
Nazıroğlu M (2011) TRPM2 cation channels, oxidative stress and neurological diseases: where are we now? Neurochem Res 36:355–366
Cory S, Adams JM (2002) The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2:647–656
Lu X, Jin C, Yang J et al (2013) Prenatal and lactational lead exposure enhanced oxidative stress and altered apoptosis status in offspring rats’ hippocampus. Biol Trace Elem Res 151:75–84
Bokara KK, Brown E, McCormick R, Yallapragada PR, Rajanna S, Bettaiya R (2008) Lead-induced increase in antioxidant enzymes and lipid peroxidation products in developing rat brain. Biometals 21:9–16
Sharifi AM, Baniasadi S, Jorjani M, Rahimi F, Bakhshayesh M (2002) Investigation of acute lead poisoning on apoptosis in rat hippocampus in vivo. Neurosci Lett 329:45–48
Sharifi AM, Mousavi SH, Jorjani M (2010) Effect of chronic lead exposure on pro-apoptotic Bax and anti-apoptotic Bcl-2 protein expression in rat hippocampus in vivo. Cell Mol Neurobiol 30:769–774
Chung D (2003) Nanoparticles have health benefits too. New Scientist 179:2410–2416
Schubert D, Dargusch R, Raitano J, Chan SW (2006) Cerium and yttrium oxide nanoparticles are neuroprotective. Biochem Biophys Res Commun 342:86–91
Hosseini A, Baeeri M, Rahimifar M et al (2013) Antiapoptotic effects of cerium oxide and yttrium oxide nanoparticles in isolated rat pancreatic islets. Hum ExpToxicol 32:544–553
Hosseini A, Abdollahi M (2012) Through a mechanism-based approach, nanoparticles of cerium and yttrium may improve the outcome of pancreatic islet isolation. J Med Hypotheses Ideas 6:4–6
Struzyñska L, Bubko I, Walski M, Rafałowska U (2001) Astroglial reaction during the early phase of acute lead toxicity in the adult rat brain. Toxicology 165:121–131
Abdel Moneim AE (2012) Flaxseed oil as a neuroprotective agent on lead acetate-induced monoamineric alterations and neurotoxicity in rats. Biol Trace Elem Res 148:363–370
Bernardi C, Tramontina AC, Nardin P et al. (2013) Treadmill exercise induces hippocampal astroglial alterations in rats. Neural Plast 2013:709732.Epub 2013 Jan 17
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358
Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77
Flora SJ, Gautam P, Kushwaha P (2012) Lead and ethanol co-exposure lead to blood oxidative stress and subsequent neuronal apoptosis in rats. Alcohol Alcohol 47:92–101
Hosseini A, Sharifzadeh M, Rezayat SM et al (2010) Benefit of magnesium-25 carrying porphyrinfullerene nanoparticles in experimental diabetic neuropathy. Int J Nanomedicine 5:517–523
Struzyńska L (2000) The protective role of astroglia in the early period of experimental lead toxicity in the rat. Acta Neurobiol Exp (Wars) 60:167–173
Han JM, Chang BJ, Li TZ et al (2007) Protective effects of ascorbic acid against lead-induced apoptotic neurodegeneration in the developing rat hippocampus in vivo. Brain Res 1185:68–74
Korsvik C, Patil S, Seal S, Self WT (2007) Superoxide dismutase mimetic properties exhibited by vacancy engineered ceria nanoparticles. Chem Commun 10:1056–1058
Rzigalinski BA, Meehan K, Davis RM, Xu Y, Miles WC, Cohen CA (2006) Radical nanomedicine. Nanomedicine (Lond) 1:399–412
Pourkhalili N, Hosseini A, Nili-Ahmadabadi A et al (2011) Biochemical and cellular evidence of the benefit of a combination of cerium oxide nanoparticles and selenium to diabetic rats. World J Diabetes 2:204–210
Das M, Patil S, Bhargava N et al (2007) Auto-catalytic ceria nanoparticles offer neuroprotection to adult rat spinal cord neurons. Biomaterials 28:1918–1925
Niu J, Azfer A, Rogers LM, Wang X, Kolattukudy PE (2007) Cardioprotective effects of cerium oxide nanoparticles in a transgenic murine model of cardiomyopathy. Cardiovasc Res 73:549–559
Colon J, Hsieh N, Ferguson A et al (2010) Cerium oxide nanoparticles protect gastrointestinal epithelium from radiation-induced damage by reduction of reactive oxygen species and upregulation of superoxide dismutase 2. Nanomedicine 6:698–705
Colon J, Herrera L, Smith J et al (2009) Protection from radiation-induced pneumonitis using cerium oxide nanoparticles. Nanomedicine 5:225–231
Tarnuzzer RW, Colon J, Patil S, Seal S (2005) Vacancy engineered ceria nanostructures for protection from radiation-induced cellular damage. Nano Lett 5:2573–2577
Chen J, Patil S, Seal S, McGinnis JF (2006) Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides. Nat Nanotechnol 1:142–150
Celardo I, De Nicola M, Mandoli C, Pedersen JZ, Traversa E, Ghibelli L (2011) Ce3+ ions determine redox-dependent anti-apoptotic effect of cerium oxide nanoparticles. ACS Nano 5:4537–4549
She JQ, Wang M, Zhu DM et al (2009) Monosialoanglioside (GM1) prevents lead-induced neurotoxicity on long-term potentiation, SOD activity, MDA levels, and intracellular calcium levels of hippocampus in rats. Naunyn Schmiedebergs Arch Pharmacol 379:517–524
Nazıroğlu M (2012) Molecular role of catalase on oxidative stress-induced Ca(2+) signaling and TRP cation channel activation in nervous system. J Recept Signal Transduct Res 32:134–141
Becker S, Soukup JM, Gallagher JE (2002) Differential particulate air pollution induced oxidant stress in human granulocytes, monocytes and alveolar macrophages. Toxicol In Vitro 16:209–218
Soltaninejad K, Kebriaeezadeh A, Minaiee B et al (2003) Biochemical and ultrastructural evidences for toxicity of lead through free radicals in rat brain. Hum ExpToxicol 22:417–423
Dribben WH, Creeley CE, Farber N (2011) Low-level lead exposure triggers neuronal apoptosis in the developing mouse brain. Neurotoxicol Teratol 33:473–480
Kiran Kumar B, PrabhakaraRao Y, Noble T et al (2009) Lead-induced alteration of apoptotic proteins in different regions of adult rat brain. Toxicol Lett 184:56–60
Flora SJ, Saxena G, Mehta A (2007) Reversal of lead-induced neuronal apoptosis by chelation treatment in rats: role of reactive oxygen species and intracellular Ca(2+). J Pharmacol Exp Ther 322:108–116
Al-Majed AA (2011) Probucol attenuates oxidative stress, energy starvation, and nitric acid production following transient forebrain ischemia in the rat hippocampus. Oxid Med Cell Longev 2011:471590
Ghazizadeh V, Nazıroğlu M (2014) Electromagnetic radiation (Wi-Fi) and epilepsy induce calcium entry and apoptosis through activation of TRPV1 channel in hippocampus and dorsal root ganglion of rats. Metab Brain Dis 29:787–799
Bennet C, Bettaiya R, Rajanna S et al (2007) Region specific increase in the antioxidant enzymes and lipid peroxidation products in the brain of rats exposed to lead. Free Radic Res 41:267–273
Adewole SO, Ayoka AO (2009) Beneficial role of Quercetin on developmental brain of rats against oxidative stress-induced poisoning. Pharmacol Online 2:1171–1184
Bagchi D, Vuchetich PJ, Bagchi M et al (1997) Induction of oxidative stress by chronic administration of sodium dichromate [chromium VI] and cadmium chloride [cadmium II] to rats. Fre Radic Biol Med 22:471–478
Xu J, Ji LD, Xu LH (2006) Lead-induced apoptosis in PC 12 cells: involvement of p53, Bcl-2 family and caspase-3. Toxicol Lett 166:160–167
Clark A, Zhu A, Sun K, Petty HR (2011) Cerium oxide and platinum nanoparticles protect cells from oxidant-mediated apoptosis. J Nanopart Res 13:5547–5555
Rafałowska U, Struzyńska L, Dabrowska-Bouta B, Lenkiewicz A (1996) Is lead toxicosis a reflection of altered energy metabolism in brain synaptosomes? Acta Neurobiol Exp (Wars) 56:611–617
Prins JM, Park S, Lurie DI (2010) Decreased expression of the voltage-dependent anion channel in differentiated PC-12 and SH-SY5Y cells following low-level Pb exposure. Toxicol Sci 113:169–176
Pourkhalili N, Hosseini A, Nili-Ahmadabadi A (2012) Improvement of isolated rat pancreatic islets function by combination of cerium oxide nanoparticles/sodium selenite through reduction of oxidative stress. Toxicol Mech Methods 22:476–482
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This study was supported by a grant from IUMS.
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Hosseini, A., Sharifi, A., Abdollahi, M. et al. Cerium and Yttrium Oxide Nanoparticles Against Lead-Induced Oxidative Stress and Apoptosis in Rat Hippocampus. Biol Trace Elem Res 164, 80–89 (2015). https://doi.org/10.1007/s12011-014-0197-z
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DOI: https://doi.org/10.1007/s12011-014-0197-z