Neuroprotective Actions of Clinoptilolite and Ethylenediaminetetraacetic Acid Against Lead"‘induced Toxicity in Mice Mus musculus
Keywords:Clinoptilolite, EDTA, lead neurotoxicity, oxidative stress
AbstractObjectives: Oxidative stress is considered as a possible molecular mechanism involved in lead (Pb2+) neurotoxicity. Very few studies have been investigated on the occurrence of oxidative stress in developing animals due to Pb2+ exposure. Considering the vulnerability of the developing brain to Pb2+, this study was carried out to investigate the effects of Pb2+ exposure in brain regions especially on antioxidant enzyme activities along with ameliorative effects of ethylenediaminetetraacetic acid (EDTA) and clinoptilolite. Methods: Three-week old developing Swiss mice Mus musculus were intraperitoneally administered with Pb2+ acetate in water (w/v) (100 mg/kg body weight/day) for 21 days and control group was given distilled water. Further Pb2+-toxicated mice were made into two subgroups and separately supplemented with EDTA and clinoptilolite (100 mg/kg body weight) for 2 weeks. Results: In Pb2+- exposed mice, in addition to increased lipid peroxidation, the activity levels of catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione (GSH) found to decrease in all regions of brain indicating, existence of severe oxidative stress due to decreased antioxidant function. Treatment of Pb2+-exposed mice with EDTA and clinoptilolite lowered the lipid peroxidation (LPO) levels revealing their antioxidant potential to prevent oxidative stress. Similarly their administration led to recover the level of catalase, SOD, and GPx enzymes affected during Pb2+ toxicity in different regions of brain. Conclusions: The protection of brain tissue against Pb2+-induced toxicity by clinoptilolite and EDTA in the present experiment might be due to their ability to react faster with peroxyl radicals there by reducing the severity of biochemical variable indicative of oxidative damage. Thus, the results of present study indicate the neuroprotective potential of clinoptilolite and EDTA against Pb2+ toxicity.
Wang XM, Liu WJ, Zhang R, Zhou YK. Effects of exposure to low"‘level lead on spatial learning and memory and the expression of mGluR1, NMDA receptor in different developmental stages of rats. Toxicol Ind Health 2012;29:686"‘96.
Rahman A, Khan KM, Al"‘Khaledi G, Khan I, Al"‘Shemary T.Over activation of hippocampal serine/threonine protein phosphatases PP1 and PP2A is involved in lead"‘induced deficits in learning and memory in young rats. Neurotoxicol 2012;33:370"‘83.
Basha R, Reddy GR. Developmental exposure to lead and late life abnormalities of nervous system. Indian J Exp Biol 2010;48:636"‘41.
Khan DA, Qayyum S, Saleem S, Khan FA. Lead"‘induced oxidative stress adversely affects health of the occupational workers.Toxicol Ind Health 2008;24:611"‘8.
Thanaa AE, Ashraf ME, Nagla AE. Possible protective effect of propolis against lead"‘induced neurotoxicity in animal model.J Evol Biol Res 2011;3:4"‘11.
Fan G, Feng C, Li Y, Wang C, Yan J, Li W, et al. Selection of nutrients for prevention or amelioration of lead"‘induced learning and memory impairment in rats. Ann Occup Hyg 2009;53:341"‘51.
Ahmad N, Hossein K, Ali Safari"‘V, Marjan R, Majid SS. Protective effect of microporous natural clinoptilolite on lead"‘induced learning and memory impairment in rats. Health Scope 2013;2:52"‘7.
Mikirova M, Casciari JJ, Hunninghake R, Riordan N. EDTA chelation therapy in treatment of toxic metal exposure.J Complement Med Drug Discov 2011;1:81"‘9.
Fatma MF. Teratogenecity and placental transfer study of lead in relation to LD50 in albino rats. N Egypt J Med 1992;3:1220"‘9.
Khalil"‘Manesh F, Gonick HC, Cohen AH. Experimental model of lead nephropathy, Continuous low"‘level lead administration.Arch Environ Health 1993;48:271"‘8.
Flora SJ, Pande M, Kanan GM, Mehta A. Lead induced oxidative stress and its recovery following co"‘administration of melatonin or N"‘acetylcystine during chelation with succimer in male rats.
Cell Mol Biol (Noisy"‘le"‘grand) 2004;50:OL543"‘51.
Balali"‘Mood M, Shademanfar S, Rastegar Moghadam J, Afshari R, Namaei Ghassemi M, Allah Nemati H, et al. Occupational lead poisoning in workers of traditional tile factories in Mashhad, Northeast of Iran. Int J Occup Environ Med 2010;1:29"‘38.
Muck"‘Seler D, Pivac N. The effect of natural clinoptilolite on the serotonergic receptors in the brain of mice with mammary carcinoma. Life Sci 2003;73:2059"‘69.
Berlin A, Schaller KH. European standardized method for the determination of delta aminolevulinic dehydratase in blood.Z Klin Chem Klin Biochem 1974;12:389"‘90.
Niehaus WG Jr, Samuelsson B. Formation of malonaldehyde from phospholipid arachidonate during microsomal lipid peroxidation. Eur J Biochem 1968;6:126"‘30.
Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972;247:3170"‘5.
Aebi H. Catalase in vitro. Methods Enzymol 1984;105:121"‘6.
Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: Biochemical role as a component of glutathione peroxidase. Science 1973;179:588"‘90.
Ellman GL. Plasma antioxidants. Arch Biochem Biophys 1959;82:70"‘7.
Lowry OH, Rosebrough NJ, Farr AL, Randal RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951;193:265"‘75.
Sanders T, Liu Y, Buchner V, Tchounwou PB. Neurotoxic effects and biomarkers of lead exposure: A review. Rev Environ Health 2009;24:15"‘45.
Rodier PM. Developing brain as a target of toxicity. Environ Health Perspect 1995;103Suppl 6:73"‘6.
Mendola P, Selevan SG, Gutter S, Rice D. Environmental factors associated with a spectrum of neurodevelopmental deficits. Ment Retard Dev Disabil Res Rev 2002;8:188"‘97.
Costa LG, Aschner M, Vitalone A, Syversen T, Soldin OP.Developmental neuropathology of environmental agents. Annu Rev Pharmacol Toxicol 2004;44:87"‘110.
Gebhart AM, Goldstein GW. Use of an in vitro system to study the effects of lead on astrocyte"‘endothelial cell interactions: A model for studying toxic injury to the blood"‘brain barrier. Toxicol Appl Pharmacol 1988;94:191"‘206.
Murata K, Iwata T, Dakeishi M, Karita K. Lead toxicity: Does the critical level of lead resulting in adverse effects differ between adults and children? J Occup Health 2009;51:1"‘12.
Bidaran SN. The effect of low concentration of lead acetate on learning ability and memory of rats during infancy and adulthood. Armaghan Danesh 2010;15:47"‘55 (In Persian).
Hu H, Shih R, Rothenberg S, Schwartz BS. The epidemiology of lead toxicity in adults: Measuring dose and consideration of other methodologic issues. Environ Health Perspect 2007;115:455"‘62.
Cecil KM, Brubaker CJ, Adler CM, Dietrich KN, Altaye M, Egelhoff JC, et al. Decreased brain volume in adults with childhood lead exposure. PLoS Med 2008;5:e112.
Siesjo BK, Agardh CD, Bengtsson F. Free radicals and brain damage. Cerebrovasc Brain Metab Rev 1989;1:165"‘211.
Nemsadze K, Sanikidze T, Ratiani L, Gabunia L, Sharashenidze T.Mechanisms of lead"‘induced poisoning. Georgian Med News 2009;172-173:92"‘6.
Ragan P, Turner T. Working to prevent lead poisoning in children: Getting the lead out. JAAPA 2009;22:40"‘5.
Flora SJ, Mittal M, Mehta A. Heavy metal induced oxidative stress and its possible reversal by chelation therapy. Indian J Med Res 2008;128:501"‘23.
Mikirova N, Casciari J, Hunninghake R. Efficacy of oral DMSA and intravenous EDTA in chelation of toxic metals and improvement of the number of stem/progenitor cells in circulation. Transl Biomed 2011;2:1"‘8.
Madhusudhan N, Basha PM, Begum S, Ahmed F. Fluoride"‘induced neuronal oxidative stress and its amelioration by antioxidants in developing rats. Fluoride 2009;42:179"‘87.
Eleroglu H Yalcin H, Yıldırım A. Dietary effects of Ca"‘zeolite supplementation on some blood and tibial bone characteristics of broilers. South Africa J Anim Sci 2011;41:319"‘30.
Safaeikatouli M, Jafariahangari Y, Baharlouei A. An evaluation on the effects of dietary kaolin and zeolite on broilers blood parameters, T4, TSH and growth hormones. Pak J Nutr 2011;10:233"‘7.
Prvulović D, Jovanović"‘Galović A, Stanić B, Popović M.Grubor"‘Lajšić G Effects of a clinoptilolite supplement in pig diets on performance and serum parameters. Czech J Anim Sci 2007;52:159"‘64.