The Role of Oxidative Stress in Metals Toxicity; Mitochondrial Dysfunction as a Key Player

Akram Ranjbar, Hassan Ghasemi, Farshad Rostampour‎
Metals can cause oxidative stress by increasing the formation of reactive oxygen species (ROS), which make antioxidants incapable of defiance against growing amounts of free radicals. Metal toxicity is related to their oxidative state and reactivity with other compounds. However, several reports about metals have been published in the recent years. Mitochondria, as a site of cellular oxygen consumption and energy production, can be a target for metals toxicity. Dysfunction of Mitochondrial oxidative phosphorylation led to the production of some metals toxicities metals through alteration in the activities of I, II, III, IV and V complexes and disruption of mitochondrial membrane. Reductions of adenosine triphosphate (ATP) synthesis or induction of its hydrolysis can impair the cellular energy production. In the present review study, the researchers have criticized reviews and some evidence about the oxidative stress as a mechanism of toxicity of metals. The metals disrupt cellular and antioxidant defense, reactive oxygen species (ROS) generation, and promote oxidative damage. The oxidative injuries induced by metals can be restored by use of antioxidants such as chelators, vitamin E and C, herbal medicine, and through increasing the antioxidants level. However, to elucidate many aspect of mechanism toxicity of metals, further studies are yet to be carried out.
Metals; Mitochondrial Dysfunction; Oxidative Stress; Reactive Oxygen Species

‎1.‎ Halliwell B. Biochemistry of oxidative stress. Biochemical Society Transactions. ‎‎2007;35(Pt 5):1147.‎

‎ Ranjbar A, Khorami S, Safarabadi M, Shahmoradi A, Malekirad AA, Vakilian K, ‎et al. Antioxidant activity of Iranian Echium amoenum Fisch & CA Mey flower ‎decoction in humans: a cross-sectional before/after clinical trial. Evidence-based ‎Complementary and Alternative Medicine. 2006;3(4):469-73.‎

‎ Guo T, Cui L, Shen J, Wang R, Zhu W, Xu Y, et al. A dual-emission and large ‎Stokes shift fluorescence probe for real-time discrimination of ROS/RNS and imaging in ‎live cells. Chemical Communications. 2013;49(18):1862-4.‎

‎ Dröge W. Free radicals in the physiological control of cell function. Physiological ‎reviews. 2002;82(1):47-95.‎

‎ Halliwell B, Gutteridge J, Cross C. Free radicals, antioxidants, and human ‎disease: where are we now? The Journal of laboratory and clinical medicine. ‎‎1992;119(6):598.‎

‎ Mittler R. Oxidative stress, antioxidants and stress tolerance. Trends in plant ‎science. 2002;7(9):405-10.‎

‎ Valko M, Rhodes C, Moncol J, Izakovic M, Mazur M. Free radicals, metals and ‎antioxidants in oxidative stress-induced cancer. Chemico-biological interactions. ‎‎2006;160(1):1-40.‎

‎ Ranjbar A, Khani-Jazani R, Sedighi A, Jalali-Mashayekhi F, Ghazi-Khansari M, ‎Abdollahi M. Alteration of body total antioxidant capacity and thiol molecules in human ‎chronic exposure to aluminum. Toxicological & Environmental Chemistry. ‎‎2008;90(4):707-13.‎

‎ Cadenas E, Davies KJ. Mitochondrial free radical generation, oxidative stress, and ‎aging. Free Radical Biology and Medicine. 2000;29(3):222-30.‎

‎ Ott M, Gogvadze V, Orrenius S, Zhivotovsky B. Mitochondria, oxidative stress ‎and cell death. Apoptosis. 2007;12(5):913-22.‎

‎ Orrenius S, Gogvadze V, Zhivotovsky B. Mitochondrial oxidative stress: ‎implications for cell death. Annu Rev Pharmacol Toxicol. 2007;47:143-83.‎

‎ Golden T-R, Melov S. Mitochondrial DNA mutations, oxidative stress, and aging. ‎Mechanisms of ageing and development. 2001;122(14):1577-89.‎

‎ Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in ‎neurodegenerative diseases. nature. 2006;443(7113):787-95.‎

‎ Krumschnabel G, Manzl C, Berger C, Hofer B. Oxidative stress, mitochondrial ‎permeability transition, and cell death in Cu-exposed trout hepatocytes. Toxicology and ‎applied pharmacology. 2005;209(1):62-73.‎

‎ Huang X, Moir RD, Tanzi RE, Bush AI, Rogers JT. Redox‐Active Metals, ‎Oxidative Stress, and Alzheimer's Disease Pathology. Annals of the New York Academy ‎of Sciences. 2004;1012(1):153-63.‎

‎ Valko M, Morris H, Cronin M. Metals, toxicity and oxidative stress. Current ‎medicinal chemistry. 2005;12(10):1161-208.‎

‎ Ercal N, Gurer-Orhan H, Aykin-Burns N. Toxic metals and oxidative stress part I: ‎mechanisms involved in metal-induced oxidative damage. Current topics in medicinal ‎chemistry. 2001;1(6):529-39.‎

‎ Jomova K, Valko M. Advances in metal-induced oxidative stress and human ‎disease. Toxicology. 2011;283(2):65-87.‎

‎ Hansford RG, Hogue BA, Mildaziene V. Dependence of H2O2 formation by rat ‎heart mitochondria on substrate availability and donor age. Journal of bioenergetics and ‎biomembranes. 1997;29(1):89-95.‎

‎ Requejo R, Chouchani ET, Hurd TR, Menger KE, Hampton MB, Murphy MP. ‎Measuring mitochondrial protein thiol redox state. Methods in enzymology. ‎‎2010;474:123-47.‎

‎ Brand MD. The sites and topology of mitochondrial superoxide production. ‎Experimental gerontology. 2010;45(7):466-72.‎

‎ Ranjbar A, Ghahremani MH, Sharifzadeh M, Golestani A, Ghazi-Khansari M, ‎Baeeri M, et al. Protection by pentoxifylline of malathion-induced toxic stress and ‎mitochondrial damage in rat brain. Human & experimental toxicology. 2010;29(10):851-‎‎64.‎

‎ Brand M. Uncoupling to survive? The role of mitochondrial inefficiency in ‎ageing. Experimental gerontology. 2000;35(6):811-20.‎

‎ Starkov AA, Fiskum G, Chinopoulos C, Lorenzo BJ, Browne SE, Patel MS, et al. ‎Mitochondrial α-ketoglutarate dehydrogenase complex generates reactive oxygen ‎species. The Journal of neuroscience. 2004;24(36):7779-88.‎

‎ Jang YC, Lustgarten MS, Liu Y, Muller FL, Bhattacharya A, Liang H, et al. ‎Increased superoxide in vivo accelerates age-associated muscle atrophy through ‎mitochondrial dysfunction and neuromuscular junction degeneration. The FASEB ‎Journal. 2010;24(5):1376-90.‎

‎ Weisiger RA, Fridovich I. Mitochondrial superoxide dismutase site of synthesis ‎and intramitochondrial localization. Journal of Biological Chemistry. 1973;248(13):4793-‎‎6.‎

‎ Liang L, Ho Y, Patel M. Mitochondrial superoxide production in kainate-induced ‎hippocampal damage. Neuroscience. 2000;101(3):563-70.‎

Sies H, Cadenas E. Oxidative stress: damage to intact cells and organs. Philos Trans R Soc Lond B Biol Sci. 1985;311(1152):617-31.

‎ Abdollahi M, Ranjbar A, Shadnia S, Nikfar S, Rezaie A. Pesticides and oxidative ‎stress: a review. Medical science monitor: international medical journal of experimental ‎and clinical research. 2004;10(6):RA141-7.‎

‎ Young I, Woodside J. Antioxidants in health and disease. Journal of clinical ‎pathology. 2001;54(3):176-86.‎

‎ Yon J-M, Baek I-J, Lee S-R, Jin Y, Kim M-R, Nahm S-S, et al. The spatio-‎temporal expression pattern of cytoplasmic Cu/Zn superoxide dismutase (SOD1) mRNA ‎during mouse embryogenesis. Journal of molecular histology. 2008;39(1):95-103.‎

‎ Fantel AG, Mackler B, Stamps LD, Tran TT, Person RE. Reactive oxygen species ‎and DNA oxidation in fetal rat tissues. Free Radical Biology and Medicine. ‎‎1998;25(1):95-103.‎

‎ Flohé L. Glutathione peroxidase. Oxygen Radicals in Biology and Medicine: ‎Springer; 1988. p. 663-8.‎

‎ Flohé L. Glutathione Peroxidases. Selenoproteins and Mimics: Springer; 2012. p. ‎‎1-25.‎

‎ Webb AJ, Patel N, Loukogeorgakis S, Okorie M, Aboud Z, Misra S, et al. Nitric ‎Oxide, Oxidative Stress. 2008.‎

‎ Stohs SJ, Bagchi D, Hassoun E, Bagchi M. Oxidative mechanisms in the toxicity ‎of chromium and cadmium ions. Journal of environmental pathology, toxicology and ‎oncology: official organ of the International Society for Environmental Toxicology and ‎Cancer. 1999;19(3):201-13.‎

‎ Barnhart J. Occurrences, uses, and properties of chromium. Regulatory toxicology ‎and pharmacology. 1997;26(1):S3-S7.‎

‎ Vincent J. The nutritional biochemistry of chromium (III): Access Online via ‎Elsevier; 2011.‎

‎ Bagchi D, Bagchi M, Stohs SJ. Chromium (VI)-induced oxidative stress, ‎apoptotic cell death and modulation of p53 tumor suppressor gene. Molecular ‎Mechanisms of Metal Toxicity and Carcinogenesis: Springer; 2001. p. 149-58.‎

‎ Mertz W. Chromium occurrence and function in biological systems. Physiol ‎Rev;(United States). 1969;49(2).‎

‎ Anderson RA. Chromium metabolism and its role in disease processes in man. ‎Clinical physiology and biochemistry. 1985;4(1):31-41.‎

‎ Wedeen RP, Qian L. Chromium-induced kidney disease. Environmental health ‎perspectives. 1991;92:71.‎

‎ Hummel M, Standl E, Schnell O. Chromium in metabolic and cardiovascular ‎disease. Hormone and metabolic research. 2007;39(10):743-51.‎

‎ Wang ZQ, Cefalu WT. Current concepts about chromium supplementation in type ‎‎2 diabetes and insulin resistance. Current diabetes reports. 2010;10(2):145-51.‎

‎ Gambelunghe A, Piccinini R, Ambrogi M, Villarini M, Moretti M, Marchetti C, et ‎al. Primary DNA damage in chrome-plating workers. Toxicology. 2003;188(2):187-95.‎

‎ Newbold R, Amos J, Connell J. The cytotoxic, mutagenic and clastogenic effects ‎of chromium-containing compounds on mammalian cells in culture. Mutation ‎Research/Genetic Toxicology. 1979;67(1):55-63.‎

‎ Levis A, Bianchi V, Tamino G, Pegoraro B. Cytotoxic effects of hexavalent and ‎trivalent chromium on mammalian cells in vitro. British journal of cancer. ‎‎1978;37(3):386.‎

‎ Vasylkiv OY, Kubrak OI, Storey KB, Lushchak VI. Cytotoxicity of chromium ‎ions may be connected with induction of oxidative stress. Chemosphere. ‎‎2010;80(9):1044-9.‎

‎ Rossi SC, Gorman N, Wetterhahn KE. Mitochondrial reduction of the carcinogen ‎chromate: formation of chromium (V). Chemical Research in Toxicology. 1988;1(2):101-‎‎7.‎

‎ Khan FH, Ambreen K, Fatima G, Kumar S. Assessment of health risks with ‎reference to oxidative stress and DNA damage in chromium exposed population. Science ‎of the Total Environment. 2012;430:68-74.‎

‎ Bagchi D, Stohs SJ, Downs BW, Bagchi M, Preuss HG. Cytotoxicity and ‎oxidative mechanisms of different forms of chromium. Toxicology. 2002;180(1):5-22.‎

‎ Peterson-Roth E, Reynolds M, Quievryn G, Zhitkovich A. Mismatch repair ‎proteins are activators of toxic responses to chromium-DNA damage. Molecular and ‎cellular biology. 2005;25(9):3596-607.‎

‎ Sugden KD, Stearns DM. The role of chromium (V) in the mechanism of ‎chromate-induced oxidative DNA damage and cancer. Journal of environmental ‎pathology, toxicology and oncology: official organ of the International Society for ‎Environmental Toxicology and Cancer. 2000;19(3):215.‎

‎ Arakawa H, Weng M-w, Chen W-c, Tang M-s. Chromium (VI) induces both ‎bulky DNA adducts and oxidative DNA damage at adenines and guanines in the p53 ‎gene of human lung cells. Carcinogenesis. 2012;33(10):1993-2000.‎

‎ Chiu A, Shi X, Lee W, Hill R, Wakeman T, Katz A, et al. Review of chromium ‎‎(VI) apoptosis, cell-cycle-arrest, and carcinogenesis. Journal of Environmental Science ‎and Health, Part C. 2010;28(3):188-230.‎

‎ Aiyar J, Borges KM, Floyd RA, Wetterhahn KE. Role of chromium (V), ‎glutathione thiyl radical and hydroxyl radical intermediates in Chromium (VI)‐induced ‎DNA Damage. Toxicological & Environmental Chemistry. 1989;22(1-4):135-48.‎

‎ Sahin K, Sahin N, Kucuk O. Effects of chromium, and ascorbic acid ‎supplementation on growth, carcass traits, serum metabolites, and antioxidant status of ‎broiler chickens reared at a high ambient temperature (32 C). Nutrition Research. ‎‎2003;23(2):225-38.‎

‎ Guha G, Rajkumar V, Kumar RA, Mathew L. Antioxidant activity of Lawsonia ‎inermis extracts inhibits chromium (VI)-induced cellular and DNA toxicity. Evidence-‎based Complementary and Alternative Medicine. 2011;2011.‎

‎ Friberg L, Piscator M, Nordberg GF, Kjellström T. Cadmium in the ‎environment1974.‎

‎ Kasuya M. Recent epidemiological studies on itai-itai disease as a chronic ‎cadmiumpoisoning in Japan. Water Science & Technology. 2000;42(7-8):147-54.‎

‎ Murata I, Hirono T, Saeki Y, Nakagawa S. Cadmium enteropathy, renal ‎osteomalacia (" Itai Itai" disease in Japan). Bulletin de la Société internationale de ‎chirurgie. 1970;29(1):34.‎

‎ Oskarsson A, Widell A, Olsson M, Grawé KP. Cadmium in food chain and health ‎effects in sensitive population groups. Biometals. 2004;17(5):531-4.‎

‎ Satarug S, Garrett SH, Sens MA, Sens DA. Cadmium, environmental exposure, ‎and health outcomes. Ciência & Saúde Coletiva. 2011;16(5):2587-602.‎

‎ Shim J, Son Y, Park JM, Kim MK. Effect of Chlorella intake on Cadmium ‎metabolism in rats. Nutrition research and practice. 2009;3(1):15-22.‎

‎ Shaikh ZA, Vu TT, Zaman K. Oxidative stress as a mechanism of chronic ‎cadmium-induced hepatotoxicity and renal toxicity and protection by antioxidants. ‎Toxicology and applied pharmacology. 1999;154(3):256-63.‎

‎ Prozialeck WC, Edwards JR, Vaidya VS, Bonventre JV. Preclinical evaluation of ‎novel urinary biomarkers of cadmium nephrotoxicity. Toxicology and applied ‎pharmacology. 2009;238(3):301-5.‎

‎ A Shaikh Z, Tang W. Protection against chronic cadmium toxicity by glycine. ‎Toxicology. 1999;132(2):139-46.‎

‎ Zhang X, Li D, Dong S, Zhang J. Study on the relationship between cadmium ‎immunotoxicity and corticotropin-releasing factor]. Wei sheng yan jiu= Journal of ‎hygiene research. 2000;29(4):193.‎

‎ Waalkes MP. Cadmium carcinogenesis. Mutation Research/Fundamental and ‎Molecular Mechanisms of Mutagenesis. 2003;533(1):107-20.‎

‎ Cuypers A, Plusquin M, Remans T, Jozefczak M, Keunen E, Gielen H, et al. ‎Cadmium stress: an oxidative challenge. Biometals. 2010;23(5):927-40.‎

‎ Liu J, Qu W, Kadiiska MB. Role of oxidative stress in cadmium toxicity and ‎carcinogenesis. Toxicology and applied pharmacology. 2009;238(3):209-14.‎

‎ Rikans LE, Yamano T. Mechanisms of cadmium‐mediated acute hepatotoxicity. ‎Journal of biochemical and molecular toxicology. 2000;14(2):110-7.‎

‎ Al-Nasser IA, Al-Nasser I. Cadmium hepatotoxicity and alterations of the ‎mitochondrial function. Clinical Toxicology. 2000;38(4):407-13.‎

‎ Li M, Xia T, Jiang C-S, Li L-J, Fu J-L, Zhou Z-C. Cadmium directly induced the ‎opening of membrane permeability pore of mitochondria which possibly involved in ‎cadmium-triggered apoptosis. Toxicology. 2003;194(1):19-33.‎

‎ Wang Y, Fang J, Leonard SS, Krishna Rao KM. Cadmium inhibits the electron ‎transfer chain and induces reactive oxygen species. Free Radical Biology and Medicine. ‎‎2004;36(11):1434-43.‎

‎ Heyno E, Klose C, Krieger‐Liszkay A. Origin of cadmium‐induced reactive ‎oxygen species production: mitochondrial electron transfer versus plasma membrane ‎NADPH oxidase. New Phytologist. 2008;179(3):687-99.‎

‎ Azzouzi BE, Tsangaris GT, Pellegrini O, Manuel Y, Benveniste J, Thomas Y. ‎Cadmium induced apoptosis in a human T cell line. Toxicology. 1994;88(1):127-39.‎

‎ Kondoh M, Araragi S, Sato K, Higashimoto M, Takiguchi M, Sato M. Cadmium ‎induces apoptosis partly via caspase-9 activation in HL-60 cells. Toxicology. ‎‎2002;170(1):111-7.‎

‎ Wang C, Ma W, Su Y. NF-κB Pathway Contributes to Cadmium-Induced ‎Apoptosis of Porcine Granulosa Cells. Biological trace element research. 2013:1-8.‎

‎ Zhang C, Mao W, Kong X, Yue L, Gao Y, Yin Z. Inhibition of cadmium-induced ‎apoptosis by Glutathione S-transferase P1 via mitogen-activated protein kinases ‎‎(MAPKs) and mitochondria. 2010.‎

‎ Fujiki K, Inamura H, Matsuoka M. Phosphorylation of FOXO3a by PI3K/Akt ‎pathway in HK-2 renal proximal tubular epithelial cells exposed to cadmium. Archives of ‎toxicology. 2013:1-9.‎

‎ Nguyen KC, Willmore WG, Tayabali AF. Cadmium telluride quantum dots cause ‎oxidative stress leading to extrinsic and intrinsic apoptosis in hepatocellular carcinoma ‎HepG2 cells. Toxicology. 2013.‎

‎ Yang Z, Yang S, Qian SY, Hong J-S, Kadiiska MB, Tennant RW, et al. ‎Cadmium-induced toxicity in rat primary mid-brain neuroglia cultures: role of oxidative ‎stress from microglia. Toxicological sciences. 2007;98(2):488-94.‎

‎ Brama M, Politi L, Santini P, Migliaccio S, Scandurra R. Cadmium-induced ‎apoptosis and necrosis in human osteoblasts: role of caspases and mitogen-activated ‎protein kinases pathways. Journal of endocrinological investigation. 2012;35(2):198.‎

‎ Patrick L. Lead toxicity, a review of the literature. Part I: exposure, evaluation, ‎and treatment. Alternative Medicine Review. 2006;11(1):2-22.‎

‎ Gidlow D. Lead toxicity. Occupational Medicine. 2004;54(2):76-81.‎

‎ Humphreys D. Effects of exposure to excessive quantities of lead on animals. ‎British Veterinary Journal. 1991;147(1):18-30.‎

‎ Sanders T, Liu Y, Buchner V, Tchounwou PB. Neurotoxic effects and biomarkers ‎of lead exposure: a review. Reviews on environmental health. 2009;24(1):15-46.‎

‎ Patra R, Swarup D, Dwivedi S. Antioxidant effects of α tocopherol, ascorbic acid ‎and L-methionine on lead induced oxidative stress to the liver, kidney and brain in rats. ‎Toxicology. 2001;162(2):81-8.‎

‎ Sandhir R, Gill K. Effect of lead on lipid peroxidation in liver of rats. Biological ‎trace element research. 1995;48(1):91-7.‎

‎ Wang L, Li J, Li J, Liu Z. Effects of lead and/or cadmium on the oxidative ‎damage of rat kidney cortex mitochondria. Biological trace element research. ‎‎2010;137(1):69-78.‎

‎ Prasanthi R, Devi CB, Basha DC, Reddy NS, Reddy GR. Calcium and zinc ‎supplementation protects lead (Pb)-induced perturbations in antioxidant enzymes and ‎lipid peroxidation in developing mouse brain. International Journal of Developmental ‎Neuroscience. 2010;28(2):161-7.‎

‎ Villeda-Hernandez J, Barroso-Moguel R, Mendez-Armenta M, Nava-Ruız C, ‎Huerta-Romero R, Rıos C. Enhanced brain regional lipid peroxidation in developing rats ‎exposed to low level lead acetate. Brain research bulletin. 2001;55(2):247-51.‎

‎ Buettner GR. The pecking order of free radicals and antioxidants: lipid ‎peroxidation, α-tocopherol, and ascorbate. Archives of Biochemistry and Biophysics. ‎‎1993;300(2):535-43.‎

‎ Daniel EE. Ameliorative Effect of Vitamin C on Serum Liver Enzymes in Lead-‎Induced Toxicity in Wistar Rats. Journal of Science. 2013;3(1):188-912.‎

‎ Bokara KK, Brown E, McCormick R, Yallapragada PR, Rajanna S, Bettaiya R. ‎Lead-induced increase in antioxidant enzymes and lipid peroxidation products in ‎developing rat brain. Biometals. 2008;21(1):9-16.‎

‎ Sugawara E, Nakamura K, Miyake T, Fukumura A, Seki Y. Lipid peroxidation ‎and concentration of glutathione in erythrocytes from workers exposed to lead. British ‎journal of industrial medicine. 1991;48(4):239-42.‎

‎ Goyer RA, Clarkson TW. Toxic effects of metals. Casarett & Doull’s Toxicology ‎The Basic Science of Poisons, Fifth Edition, Klaassen, CD [Ed] McGraw-Hill Health ‎Professions Division, ISBN. 1996;71054766.‎

‎ Ullah N, Khan MF, Mukhtiar M, Khan H, Rehman AU. Metabolic modulation of ‎glutathione in whole blood components against lead-induced toxicity. African Journal of ‎Biotechnology. 2011;10(77):17853-8.‎

‎ Campana O, Sarasquete C, Blasco J. Effect of lead on ALA-D activity, ‎metallothionein levels, and lipid peroxidation in blood, kidney, and liver of the toadfish< ‎i> Halobatrachus didactylus. Ecotoxicology and Environmental Safety. ‎‎2003;55(1):116-25.‎

‎ Jiun YS, Hsien LT. Lipid peroxidation in workers exposed to lead. Archives of ‎Environmental Health: An International Journal. 1994;49(4):256-9.‎

‎ Gurer-Orhan H, Sabır HU, Özgüneş H. Correlation between clinical indicators of ‎lead poisoning and oxidative stress parameters in controls and lead-exposed workers. ‎Toxicology. 2004;195(2):147-54.‎

‎ Rocha JB, Pereira ME, Emanuelli T, Christofari RS, Souz DO. Effect of treatment ‎with mercury chloride and lead acetate during the second stage of rapid postnatal brain ‎growth on δ-aminolevulinic acid dehydratase (ALA-D) activity in brain, liver, kidney and ‎blood of suckling rats. Toxicology. 1995;100(1):27-37.‎

‎ Rodriguez BL, Curb JD, Davis J, Shintani T, Perez MH, Apau‐Ludlum N, et al. ‎Use of the Dietary Supplement 5‐Aminiolevulinic Acid (5‐ALA) and Its Relationship ‎with Glucose Levels and Hemoglobin A1C among Individuals with Prediabetes. Clinical ‎and Translational Science. 2012;5(4):314-20.‎

‎ Ahamed M, Siddiqui M. Low level lead exposure and oxidative stress: current ‎opinions. Clinica Chimica Acta. 2007;383(1):57-64.‎

‎ Young KW, Piñon LG, Bampton ET, Nicotera P. Different pathways lead to ‎mitochondrial fragmentation during apoptotic and excitotoxic cell death in primary ‎neurons. Journal of biochemical and molecular toxicology. 2010;24(5):335-41.‎

‎ He L, Poblenz AT, Medrano CJ, Fox DA. Lead and calcium produce rod ‎photoreceptor cell apoptosis by opening the mitochondrial permeability transition pore. ‎Journal of Biological Chemistry. 2000;275(16):12175-84.‎

‎ Liu Z, Li D, Zhao W, Zheng X, Wang J, Wang E. A potent lead induces apoptosis ‎in pancreatic cancer cells. PloS one. 2012;7(6):e37841.‎

‎ Hsu P-C, Guo YL. Antioxidant nutrients and lead toxicity. Toxicology. ‎‎2002;180(1):33-44.‎

‎ Gargouri M, Magné C, Dauvergne X, Ksouri R, El Feki A, Metges M-AG, et al. ‎Cytoprotective and antioxidant effects of the edible halophyte< i> Sarcocornia ‎perennis L.(swampfire) against lead-induced toxicity in renal cells. Ecotoxicology ‎and Environmental Safety. 2013.‎

‎ Berlyne G, Ben Ari J, Knopf E, Yagil R, Weinberger G, Danovitch G. Aluminium ‎toxicity in rats. The Lancet. 1972;299(7750):564-8.‎

‎ Boscolo PR, Menossi M, Jorge RA. Aluminum-induced oxidative stress in maize. ‎Phytochemistry. 2003;62(2):181-9.‎

‎ Xie CX, Mattson MP, Lovell MA, Yokel RA. Intraneuronal aluminum potentiates ‎iron-induced oxidative stress in cultured rat hippocampal neurons. Brain research. ‎‎1996;743(1):271-7.‎

‎ Sood PK, Nahar U, Nehru B. Curcumin attenuates aluminum-induced oxidative ‎stress and mitochondrial dysfunction in rat brain. Neurotoxicity research. ‎‎2011;20(4):351-61.‎

‎ Flora SJ, Mehta A, Satsangi K, Kannan GM, Gupta M. Aluminum-induced ‎oxidative stress in rat brain: Response to combined administration of citric acid and ‎HEDTA. Comparative Biochemistry and Physiology Part C: Toxicology & ‎Pharmacology. 2003;134(3):319-28.‎

‎ Mahieu ST, Gionotti M, Millen N, Elías MM. Effect of chronic accumulation of ‎aluminum on renal function, cortical renal oxidative stress and cortical renal organic ‎anion transport in rats. Archives of toxicology. 2003;77(11):605-12.‎

‎ Wang H, Liang W, Huang J. Putrescine Mediates Aluminum Tolerance in Red ‎Kidney Bean by Modulating Aluminum-Induced Oxidative Stress. Crop Science. 2013.‎

‎ Federico A, Cardaioli E, Da Pozzo P, Formichi P, Gallus GN, Radi E. ‎Mitochondria, oxidative stress and neurodegeneration. Journal of the neurological ‎sciences. 2012;322(1):254-62.‎

‎ Niemi NM, MacKeigan JP. Mitochondrial Phosphorylation in Apoptosis: Flipping ‎the Death Switch. Antioxidants & redox signaling. 2012.‎

‎ Li Z, Xing D. Mechanistic study of mitochondria-dependent programmed cell ‎death induced by aluminium phytotoxicity using fluorescence techniques. Journal of ‎experimental botany. 2011;62(1):331-43.‎

‎ Kumar V, Bal A, Gill KD. Impairment of mitochondrial energy metabolism in ‎different regions of rat brain following chronic exposure to aluminium. Brain research. ‎‎2008;1232:94-103.‎

‎ Bharathi VP, Govindaraju M, Palanisamy A, Sambamurti K, Rao K. Molecular ‎toxicity of aluminium in relation to neurodegeneration. Indian J Med Res. ‎‎2008;128(4):545-56.‎

‎ Schildknecht PH, Vidal BC. Aluminium triggers necrosis and apoptosis in V79 ‎cells. Toxicological & Environmental Chemistry. 2004;86(1):63-72.‎

‎ Gupta VB, Anitha S, Hegde M, Zecca L, Garruto R, Ravid R, et al. Aluminium in ‎Alzheimer’s disease: are we still at a crossroad? Cellular and Molecular Life Sciences ‎CMLS. 2005;62(2):143-58.‎

‎ El-Demerdash FM. Antioxidant effect of vitamin E and selenium on lipid ‎peroxidation, enzyme activities and biochemical parameters in rats exposed to ‎aluminium. Journal of Trace Elements in Medicine and Biology. 2004;18(1):113-21.‎

‎ Silva S, Pinto G, Correia B, Pinto-Carnide O, Santos C. Rye oxidative stress ‎under long term Al exposure. Journal of plant physiology. 2013.‎

‎ Rottkamp CA, Nunomura A, Raina AK, Sayre LM, Perry G, Smith MA. ‎Oxidative stress, antioxidants, and Alzheimer disease. Alzheimer Disease & Associated ‎Disorders. 2000;14(1):S62-S6.‎

‎ Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial ROS-induced ROS release: an ‎update and review. Biochimica et Biophysica Acta (BBA)-Bioenergetics. ‎‎2006;1757(5):509-17.‎

‎ Blokhina O, Virolainen E, Fagerstedt KV. Antioxidants, oxidative damage and ‎oxygen deprivation stress: a review. Annals of botany. 2003;91(2):179-94.‎

‎ Klaunig JE, Kamendulis LM, Hocevar BA. Oxidative stress and oxidative ‎damage in carcinogenesis. Toxicologic pathology. 2010;38(1):96-109.‎

‎ Halliwell B, Gutteridge J. Free radicals in biology and medicine. Pergamon; 1985.‎

‎ Costa M. Dioxygenases as Targets of Metals, Hypoxia and Oxidative Stress ‎during Carcinogenesis. Journal of Molecular and Genetic Medicine. 2013.‎

‎ Bahavar M, Tarbali N, Einolahi N, Dashti N. Evaluation of trace metal (cd, cr, ‎cu)–induced oxidative stress in presence of H2O2 on purified DNA strands break from ‎nonpathogenic Escherichia coli. KAUMS Journal (FEYZ). 2013;16(7):633-4.‎

‎ Belyaeva EA, Sokolova TV, Emelyanova LV, Zakharova

IO. Mitochondrial ‎electron transport chain in heavy metal-induced neurotoxicity: effects of cadmium, ‎mercury, and copper. The Scientific World Journal. 2012;2012.‎

‎ Pulido MD, Parrish AR. Metal-induced apoptosis: mechanisms. Mutation ‎Research/Fundamental and Molecular Mechanisms of Mutagenesis. 2003;533(1):227-41.‎

‎ Granchi D, Cenni E, Ciapetti G, Savarino L, Stea S, Gamberini S, et al. Cell death ‎induced by metal ions: necrosis or apoptosis? Journal of materials science: materials in ‎medicine. 1998;9(1):31-7.‎

‎ Shi H, Hudson LG, Liu KJ. Oxidative stress and apoptosis in metal ion-induced ‎carcinogenesis. Free Radical Biology and Medicine. 2004;37(5):582-93.‎

‎ Kasprzak KS. Possible role of oxidative damage in metal-induced carcinogenesis. ‎Cancer investigation. 1995;13(4):411-30.‎

‎ Martinez-Zamudio R, Ha HC. Environmental epigenetics in metal exposure. ‎Epigenetics. 2011;6(7):820-7.‎

‎ Patrick L. Toxic metals and antioxidants: Part II. The role of antioxidants in ‎arsenic and cadmium toxicity. Alternative Medicine Review. 2003;8(2):106-28.‎

‎ Kostova I, Balkansky S. Metal Complexes of Biologically Active Ligands as ‎Potential Antioxidants. Current medicinal chemistry. 2013.‎

‎ Gaurav D, Preet S, Dua K. Chronic cadmium toxicity in rats: Treatment with ‎combined administration of vitamins, amino acids, antioxidants and essential metals. ‎Journal of Food and Drug Analysis. 2010;18(6):464-70.‎

‎ Pham-Huy LA, He H, Pham-Huy C. Free radicals, antioxidants in disease and ‎health. International journal of biomedical science: IJBS. 2008;4(2):89.‎

‎ Tavakol HS, Akram R, Azam S, Nahid Z. Protective effects of green tea on ‎antioxidative biomarkers in chemical laboratory workers. Toxicology and Industrial ‎Health. 2013.‎

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