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Ototoxicity of Divalent Metals

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Abstract

Excess exposure to both essential and non-essential heavy metals can lead to a variety of adverse clinical conditions which selectively affect a variety of organs and cells in the body. The diverse, but highly specific nature of the symptoms produced by each metal indicates that they can interact with a restricted population of cellular targets ultimately resulting in unique clinical manifestations. The symptoms, which can be reversible or irreversible, often present with different patterns and outcomes depending on the net accumulated dose of any given metal. There are some common pathological conditions that result from excess exposure to heavy metals which unfortunately have not received widespread recognition and thus, have not been extensively investigated. For example, chronic exposure to several heavy metals such as Co, Mn, Cd, Pb, and Hg has the potential to affect hearing in humans and experimental animals based on previous studies including case reports and ex vivo studies. Understanding exactly how these metals induce hearing deficits is complicated by the fact that the inner ear is an extremely complex system that composed of a diverse collection of sensory, neural, and supporting cells which must act in synchrony to produce a neurophysiological signal terminating in the central auditory system. This review will focus on the anatomical, cellular, and functional changes that occur in the cochlea, the sensory organ for hearing, due to excessive exposure to manganese, cadmium, cobalt, lead, and mercury.

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References

  • Adachi T, Aida K, Nishihara H, Kamiya T, Hara H (2011) Effect of hypoxia mimetic cobalt chloride on the expression of extracellular-superoxide dismutase in retinal pericytes. Biol Pharm Bull 34:1297–1300

    Article  CAS  PubMed  Google Scholar 

  • Agirdir BV, Bilgen I, Dinc O, Ozcaglar HU, Fisenk F, Turhan M et al (2002) Effect of zinc ion on cadmium-induced auditory changes. Biol Trace Elem Res 88:153–163

    Article  CAS  PubMed  Google Scholar 

  • Agrawal S, Flora G, Bhatnagar P, Flora SJ (2014) Comparative oxidative stress, metallothionein induction and organ toxicity following chronic exposure to arsenic, lead and mercury in rats. Cell Mol Biol (Noisy-le-grand) 60:13–21

    CAS  Google Scholar 

  • Ahamed M, Siddiqui MK (2007) Low level lead exposure and oxidative stress: current opinions. Clin Chim Acta 383:57–64

    Article  CAS  PubMed  Google Scholar 

  • Aimola P, Carmignani M, Volpe AR, Di Benedetto A, Claudio L, Waalkes MP et al (2012) Cadmium induces p53-dependent apoptosis in human prostate epithelial cells. PLoS ONE 7:e33647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anderson M (1983) Mn ions pass through calcium channels. A possible explanation. J Gen Physiol 81:805–827

    Article  CAS  PubMed  Google Scholar 

  • Anniko M, Sarkady L (1978) Cochlear pathology following exposure to mercury. Acta Otolaryngol 85:213–224

    Article  CAS  PubMed  Google Scholar 

  • Antonini JM (2003) Health effects of welding. Crit Rev Toxicol 33:61–103

    Article  CAS  PubMed  Google Scholar 

  • Antonini JM, Sriram K, Benkovic SA, Roberts JR, Stone S, Chen BT et al (2009) Mild steel welding fume causes manganese accumulation and subtle neuroinflammatory changes but not overt neuronal damage in discrete brain regions of rats after short-term inhalation exposure. Neurotoxicology 30:915–925

    Article  CAS  PubMed  Google Scholar 

  • Antonini JM, Zeidler-Erdely PC, Young SH, Roberts JR, Erdely A (2012) Systemic immune cell response in rats after pulmonary exposure to manganese-containing particles collected from welding aerosols. J Immunotoxicol 9:184–192

    Article  CAS  PubMed  Google Scholar 

  • Apostoli P, Catalani S, Zaghini A, Mariotti A, Poliani PL, Vielmi V et al (2013) High doses of cobalt induce optic and auditory neuropathy. Exp Toxicol Pathol 65:719–727

    Article  CAS  PubMed  Google Scholar 

  • Banci L, Bertini I, Ciofi-Baffoni S, Su XC, Miras R, Bal N et al (2006) Structural basis for metal binding specificity: the N-terminal cadmium binding domain of the P1-type ATPase CadA. J Mol Biol 356:638–650

    Article  CAS  PubMed  Google Scholar 

  • Basinger MA, Jones MM, Craft WD, Walker EM Jr, Sanders MM (1987) Chelating-agent suppression of cadmium-induced hepatotoxicity. J Toxicol Environ Health 22:261–271

    Article  CAS  PubMed  Google Scholar 

  • Battaglia V, Compagnone A, Bandino A, Bragadin M, Rossi CA, Zanetti F et al (2009) Cobalt induces oxidative stress in isolated liver mitochondria responsible for permeability transition and intrinsic apoptosis in hepatocyte primary cultures. Int J Biochem Cell Biol 41:586–594

    Article  CAS  PubMed  Google Scholar 

  • Bencko V, Cikrt M (1984) Manganese: a review of occupational and environmental toxicology. J Hyg Epidemiol Microbiol Immunol 28:139–148

    CAS  PubMed  Google Scholar 

  • Bertin G, Averbeck D (2006) Cadmium: cellular effects, modifications of biomolecules, modulation of DNA repair and genotoxic consequences (a review). Biochimie 88:1549–1559

    Article  CAS  PubMed  Google Scholar 

  • Bouchard M, Mergler D, Baldwin ME, Panisset M (2008) Manganese cumulative exposure and symptoms: a follow-up study of alloy workers. Neurotoxicology 29:577–583

    Article  CAS  PubMed  Google Scholar 

  • Bourre JM (2006) Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 1: micronutrients. J Nutr Health Aging 10:377–385

    CAS  PubMed  Google Scholar 

  • Bowler RM, Roels HA, Nakagawa S, Drezgic M, Diamond E, Park R et al (2007) Dose-effect relationships between manganese exposure and neurological, neuropsychological and pulmonary function in confined space bridge welders. Occup Environ Med 64:167–177

    Article  CAS  PubMed  Google Scholar 

  • Bradberry SM, Wilkinson JM, Ferner RE (2014) Systemic toxicity related to metal hip prostheses. Clin Toxicol (Phila) 52:837–847

    Article  CAS  Google Scholar 

  • Branco V, Canario J, Lu J, Holmgren A, Carvalho C (2012) Mercury and selenium interaction in vivo: effects on thioredoxin reductase and glutathione peroxidase. Free Radic Biol Med 52:781–793

    Article  CAS  PubMed  Google Scholar 

  • Bressler JP, Olivi L, Cheong JH, Kim Y, Bannona D (2004) Divalent metal transporter 1 in lead and cadmium transport. Ann N Y Acad Sci 1012:142–152

    Article  CAS  PubMed  Google Scholar 

  • Burkhard PR, Delavelle J, Du Pasquier R, Spahr L (2003) Chronic Parkinsonism associated with cirrhosis: a distinct subset of acquired hepatocerebral degeneration. Arch Neurol 60:521–528

    Article  PubMed  Google Scholar 

  • Chabicovsky M, Klepal W, Dallinger R (2004) Mechanisms of cadmium toxicity in terrestrial pulmonates: programmed cell death and metallothionein overload. Environ Toxicol Chem 23:648–655

    Article  CAS  PubMed  Google Scholar 

  • Chao JI, Yang JL (2001) Opposite roles of ERK and p38 mitogen-activated protein kinases in cadmium-induced genotoxicity and mitotic arrest. Chem Res Toxicol 14:1193–1202

    Article  CAS  PubMed  Google Scholar 

  • Chatterjee S, Kundu S, Sengupta S, Bhattacharyya A (2009) Divergence to apoptosis from ROS induced cell cycle arrest: effect of cadmium. Mutat Res 663:22–31

    Article  CAS  PubMed  Google Scholar 

  • Chen CJ, Liao SL (2002) Oxidative stress involves in astrocytic alterations induced by manganese. Exp Neurol 175:216–225

    Article  CAS  PubMed  Google Scholar 

  • Choong G, Liu Y, Templeton DM (2014) Interplay of calcium and cadmium in mediating cadmium toxicity. Chem Biol Interact 211:54–65

    Article  CAS  PubMed  Google Scholar 

  • Chu CC, Huang CC, Ryu SJ, Wu TN (1998) Chronic inorganic mercury induced peripheral neuropathy. Acta Neurol Scand 98:461–465

    Article  CAS  PubMed  Google Scholar 

  • Chun HS, Lee H, Son JH (2001) Manganese induces endoplasmic reticulum (ER) stress and activates multiple caspases in nigral dopaminergic neuronal cells, SN4741. Neurosci Lett 316:5–8

    Article  CAS  PubMed  Google Scholar 

  • Clarkson TW (1993) Mercury: major issues in environmental health. Environ Health Perspect 100:31–38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Counter SA, Buchanan LH (2002) Neuro-ototoxicity in Andean adults with chronic lead and noise exposure. J Occup Environ Med 44:30–38

    Article  CAS  PubMed  Google Scholar 

  • Counter SA, Buchanan LH, Ortega F (2009a) Neurocognitive screening of lead-exposed andean adolescents and young adults. J Toxicol Environ Health A 72:625–632

    Article  CAS  PubMed  Google Scholar 

  • Counter SA, Buchanan LH, Ortega F (2009b) Neurophysiologic and neurocognitive case profiles of Andean patients with chronic environmental lead poisoning. J Toxicol Environ Health A 72:1150–1159

    Article  CAS  PubMed  Google Scholar 

  • Couper J (1837) On the effects of black oxide of manganese when inhaled into the lungs. Br Ann Med Pharm Vital Stat Gen Sci 1:41–42

    Google Scholar 

  • Coutant A, Lebeau J, Bidon-Wagner N, Levalois C, Lectard B, Chevillard S (2006) Cadmium-induced apoptosis in lymphoblastoid cell line: involvement of caspase-dependent and -independent pathways. Biochimie 88:1815–1822

    Article  CAS  PubMed  Google Scholar 

  • Da Silva CJDRAJ, Jeronymo S, Mendes MF, Milani FT, Maia AC, Jr Braga FT, Sens YA, Miorin LA (2007) A preliminary study revealing a new association in patients undergoing maintenance hemodialysis: manganism symptoms and T1 hyperintense changes in the basal ganglia. Am J Neuroradiol 28:1474–1479

    Article  PubMed  Google Scholar 

  • Desole MS, Esposito G, Migheli R, Sircana S, Delogu MR, Fresu L et al (1997) Glutathione deficiency potentiates manganese toxicity in rat striatum and brainstem and in PC12 cells. Pharmacol Res 36:285–292

    Article  CAS  PubMed  Google Scholar 

  • Dietrich KN, Succop PA, Berger OG, Keith RW (1992) Lead exposure and the central auditory processing abilities and cognitive development of urban children: the Cincinnati Lead Study cohort at age 5 years. Neurotoxicol Teratol 14:51–56

    Article  CAS  PubMed  Google Scholar 

  • Ding J, Gong S (2004) The expression and significance of VIP and SP in the cochlea of rats. Lin Chuang Er Bi Yan Hou Ke Za Zhi 18(681–2):4

    Google Scholar 

  • Ding D, Jiang H, Wang P, Salvi R (2007) Cell death after co-administration of cisplatin and ethacrynic acid. Hear Res 226:129–139

    Article  CAS  PubMed  Google Scholar 

  • Ding D, Roth J, Salvi R (2011) Manganese is toxic to spiral ganglion neurons and hair cells in vitro. Neurotoxicology 32:233–241

    Article  CAS  PubMed  Google Scholar 

  • Ding D, Salvi R, Roth JA (2014a) Cellular localization and developmental changes of the different isoforms of divalent metal transporter 1 (DMT1) in the inner ear of rats. Biometals 27:125–134

    Article  CAS  PubMed  Google Scholar 

  • Ding D, Salvi R, Roth JA (2014b) Cellular localization and developmental changes of Zip8, Zip14 and transferrin receptor 1 in the inner ear of rats. Biometals 27:731–744

    Article  CAS  PubMed  Google Scholar 

  • Donaldson JD, Beyersmann D (2005) Cobalt and cobalt compounds. Ulmann’s encyclopedia of industrial chemistry. Wiley-VCH, Weinheim

    Google Scholar 

  • Flora SJ (2002) Lead exposure: health effects, prevention and treatment. J Environ Biol 23:25–41

    CAS  PubMed  Google Scholar 

  • Fujishiro H, Yano Y, Takada Y, Tanihara M, Himeno S (2012) Roles of ZIP8, ZIP14, and DMT1 in transport of cadmium and manganese in mouse kidney proximal tubule cells. Metallomics 4:700–708

    Article  CAS  PubMed  Google Scholar 

  • Garrick MD, Singleton ST, Vargas F, Kuo HC, Zhao L, Knopfel M et al (2006) DMT1: which metals does it transport? Biol Res 39:79–85

    Article  CAS  PubMed  Google Scholar 

  • Garrick MD, Zhao L, Roth JA, Jiang H, Feng J, Foot NJ et al (2012) Isoform specific regulation of divalent metal (ion) transporter (DMT1) by proteasomal degradation. Biometals 25:787–793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garza A, Vega R, Soto E (2006) Cellular mechanisms of lead neurotoxicity. Med Sci Monit 12:RA57–RA65

    PubMed  Google Scholar 

  • Gavin CE, Gunter KK, Gunter TE (1990) Manganese and calcium efflux kinetics in brain mitochondria. Relevance to manganese toxicity. Biochem J 266:329–334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gavin CE, Gunter KK, Gunter TE (1999) Manganese and calcium transport in mitochondria: implications for manganese toxicity. Neurotoxicology 20:445–453

    CAS  PubMed  Google Scholar 

  • Hamada T, Tanimoto A, Sasaguri Y (1997) Apoptosis induced by cadmium. Apoptosis 2:359–367

    Article  CAS  PubMed  Google Scholar 

  • Hauser RA, Zesiewicz TA (1996) Manganese and chronic liver disease. Mov Disord 11:589

    Article  CAS  PubMed  Google Scholar 

  • Hauser RA, Zesiewicz TA, Rosemurgy AS, Martinez C, Olanow CW (1994) Manganese intoxication and chronic liver failure. Ann Neurol 36:871–875

    Article  CAS  PubMed  Google Scholar 

  • Herber RF (1992) The World Health Organization study on health effects of exposure to cadmium: morbidity studies. IARC Sci Publ 118:347–358

    CAS  PubMed  Google Scholar 

  • Hirata Y, Adachi K, Kiuchi K (1998) Activation of JNK pathway and induction of apoptosis by manganese in PC12 cells. J Neurochem 71:1607–1615

    Article  CAS  PubMed  Google Scholar 

  • Hoshino AC, Ferreira HP, Malm O, Carvallo RM, Camara VM (2012) A systematic review of mercury ototoxicity. Cad Saude Publica 28:1239–1248

    Article  PubMed  Google Scholar 

  • Hsu PC, Liu MY, Hsu CC, Chen LY, Guo YL (1997) Lead exposure causes generation of reactive oxygen species and functional impairment in rat sperm. Toxicology 122:133–143

    Article  CAS  PubMed  Google Scholar 

  • Huang CC, Lu CS, Chu NS, Hochberg F, Lilienfeld D, Olanow W et al (1993) Progression after chronic manganese exposure. Neurology 43:1479–1483

    Article  CAS  PubMed  Google Scholar 

  • Huang PC, Su PH, Chen HY, Huang HB, Tsai JL, Huang HI et al (2012) Childhood blood lead levels and intellectual development after ban of leaded gasoline in Taiwan: a 9-year prospective study. Environ Int 40:88–96

    Article  CAS  PubMed  Google Scholar 

  • Huff J, Lunn RM, Waalkes MP, Tomatis L, Infante PF (2007) Cadmium-induced cancers in animals and in humans. Int J Occup Environ Health 13:202–212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Humes HD (1999) Insights into ototoxicity. Analogies to nephrotoxicity. Ann N Y Acad Sci 884:15–18

    CAS  PubMed  Google Scholar 

  • Hurley LS (1981) The roles of trace elements in foetal and neonatal development. Philos Trans R Soc Lond B Biol Sci 294:145–152

    Article  CAS  PubMed  Google Scholar 

  • Igarashi S, Koide C, Sasaki H, Nakano Y (1992) Mercury deposition and its relationship to inner ear function in methylmercury-poisoned rats. A histological and immunohistochemical study. Acta Otolaryngol 112:773–778

    Article  CAS  PubMed  Google Scholar 

  • Ikeda T, Takahashi K, Kabata T, Sakagoshi D, Tomita K, Yamada M (2010) Polyneuropathy caused by cobalt-chromium metallosis after total hip replacement. Muscle Nerve 42:140–143

    Article  PubMed  Google Scholar 

  • Illing AC, Shawki A, Cunningham CL, Mackenzie B (2012) Substrate profile and metal-ion selectivity of human divalent metal-ion transporter-1. J Biol Chem 287:30485–30496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jenkitkasemwong S, Wang CY, Mackenzie B, Knutson MD (2012) Physiologic implications of metal-ion transport by ZIP14 and ZIP8. Biometals 25:643–655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones LG, Prins J, Park S, Walton JP, Luebke AE, Lurie DI (2008) Lead exposure during development results in increased neurofilament phosphorylation, neuritic beading, and temporal processing deficits within the murine auditory brainstem. J Comp Neurol 506:1003–1017

    Article  CAS  PubMed  Google Scholar 

  • Josephs KA, Ahlskog JE, Klos KJ, Kumar N, Fealey RD, Trenerry MR et al (2005) Neurologic manifestations in welders with pallidal MRI T1 hyperintensity. Neurology 64:2033–2039

    Article  CAS  PubMed  Google Scholar 

  • Kannurpatti SS, Joshi PG, Joshi NB (2000) Calcium sequestering ability of mitochondria modulates influx of calcium through glutamate receptor channel. Neurochem Res 25:1527–1536

    Article  CAS  PubMed  Google Scholar 

  • Karovic O, Tonazzini I, Rebola N, Edstrom E, Lovdahl C, Fredholm BB et al (2007) Toxic effects of cobalt in primary cultures of mouse astrocytes. Similarities with hypoxia and role of HIF-1alpha. Biochem Pharmacol 73:694–708

    Article  CAS  PubMed  Google Scholar 

  • Keen CL, Ensunsa JL, Watson MH, Baly DL, Donovan SM, Monaco MH et al (1999) Nutritional aspects of manganese from experimental studies. Neurotoxicology 20:213–223

    CAS  PubMed  Google Scholar 

  • Kemmerer AR, Elvehjem CA, Hart EB (1931) Studies on the relation of manganese to the nutrition of the mouse. J Biol Chem 92:623–630

    CAS  Google Scholar 

  • Khalkova Z, Kostadinova G (1986) Auditory-vestibular changes in workers in ferrous metallurgy manufacture. Probl Khig 11:134–138

    PubMed  Google Scholar 

  • Kim HJ, Yang SJ, Kim YS, Kim TU (2003) Cobalt chloride-induced apoptosis and extracellular signal-regulated protein kinase activation in human cervical cancer HeLa cells. J Biochem Mol Biol 36:468–474

    Article  CAS  PubMed  Google Scholar 

  • Kim SJ, Jeong HJ, Myung NY, Kim MC, Lee JH, So HS et al (2008) The protective mechanism of antioxidants in cadmium-induced ototoxicity in vitro and in vivo. Environ Health Perspect 116:854–862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim SJ, Shin BG, Choi IY, Kim DH, Kim MC, Myung NY et al (2009) Hwanggunchungyitang prevents cadmium-induced ototoxicity through suppression of the activation of caspase-9 and extracellular signal-related kinase in auditory HEI-OC1 cells. Biol Pharm Bull 32:213–219

    Article  CAS  PubMed  Google Scholar 

  • Kitazawa M, Anantharam V, Yang Y, Hirata Y, Kanthasamy A, Kanthasamy AG (2005) Activation of protein kinase C delta by proteolytic cleavage contributes to manganese-induced apoptosis in dopaminergic cells: protective role of Bcl-2. Biochem Pharmacol 69:133–146

    Article  CAS  PubMed  Google Scholar 

  • Koizumi T, Shirakura H, Kumagai H, Tatsumoto H, Suzuki KT (1996) Mechanism of cadmium-induced cytotoxicity in rat hepatocytes: cadmium-induced active oxygen-related permeability changes of the plasma membrane. Toxicology 114:125–134

    Article  CAS  PubMed  Google Scholar 

  • Korczynski RE (2000) Occupational health concerns in the welding industry. Appl Occup Environ Hyg 15:936–945

    Article  CAS  PubMed  Google Scholar 

  • Krieger D, Krieger S, Jansen O, Gass P, Theilmann L, Lichtnecker H (1995) Manganese and chronic hepatic encephalopathy. Lancet 346:270–274

    Article  CAS  PubMed  Google Scholar 

  • Kuriyama H, Jenkins O, Altschuler RA (1994) Immunocytochemical localization of AMPA selective glutamate receptor subunits in the rat cochlea. Hear Res 80:233–240

    Article  CAS  PubMed  Google Scholar 

  • Lasfer M, Vadrot N, Aoudjehane L, Conti F, Bringuier AF, Feldmann G et al (2008) Cadmium induces mitochondria-dependent apoptosis of normal human hepatocytes. Cell Biol Toxicol 24:55–62

    Article  CAS  PubMed  Google Scholar 

  • Leonard S, Gannett PM, Rojanasakul Y, Schwegler-Berry D, Castranova V, Vallyathan V et al (1998) Cobalt-mediated generation of reactive oxygen species and its possible mechanism. J Inorg Biochem 70:239–244

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Ding D, Jiang H, Fu Y, Salvi R (2011) Co-administration of cisplatin and furosemide causes rapid and massive loss of cochlear hair cells in mice. Neurotox Res 20:307–319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li P, Ding D, Salvi R, Roth JA (2015) Cobalt-induced ototoxicity in rat postnatal cochlear organotypic cultures. Neurotox Res 28:209–221

    Article  CAS  PubMed  Google Scholar 

  • Liang GH, Jarlebark L, Ulfendahl M, Moore EJ (2003) Mercury (Hg2+) suppression of potassium currents of outer hair cells. Neurotoxicol Teratol 25:349–359

    Article  CAS  PubMed  Google Scholar 

  • Lidsky TI, Schneider JS (2003) Lead neurotoxicity in children: basic mechanisms and clinical correlates. Brain 126:5–19

    Article  PubMed  Google Scholar 

  • Liu S, Zhang K, Wu S, Ji X, Li N, Liu R et al (2011) Lead-induced hearing loss in rats and the protective effect of copper. Biol Trace Elem Res 144:1112–1119

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Zheng G, Wu Y, Shen X, Jing J, Yu T et al (2013) Lead exposure results in hearing loss and disruption of the cochlear blood–labyrinth barrier and the protective role of iron supplement. Neurotoxicology 39:173–181

    Article  CAS  PubMed  Google Scholar 

  • Liu H, Ding D, Sun H, Jiang H, Wu X, Roth JA et al (2014) Cadmium-induced ototoxicity in rat cochlear organotypic cultures. Neurotox Res 26:179–189

    Article  CAS  PubMed  Google Scholar 

  • Lobarinas E, Salvi R, Ding D (2013) Insensitivity of the audiogram to carboplatin induced inner hair cell loss in chinchillas. Hear Res 302:113–120

    Article  CAS  PubMed  Google Scholar 

  • Lopes AC, Peixe TS, Mesas AE, Paoliello MM (2016) Lead exposure and oxidative stress: a systematic review. Rev Environ Contam Toxicol 236:193–238

    PubMed  Google Scholar 

  • Lucchini RG, Martin CJ, Doney BC (2009) From manganism to manganese-induced parkinsonism: a conceptual model based on the evolution of exposure. Neuromol Med 11:311–321

    Article  CAS  Google Scholar 

  • Ma C, Schneider SN, Miller M, Nebert DW, Lind C, Roda SM et al (2008) Manganese accumulation in the mouse ear following systemic exposure. J Biochem Mol Toxicol 22:305–310

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Malva JO, Vieira AP, Ambrosio AF, Oliveira CR (2003) Cobalt staining of hippocampal neurons mediated by non-desensitizing activation of AMPA but not kainate receptors. NeuroReport 14:847–850

    Article  CAS  PubMed  Google Scholar 

  • Martinez-Finley EJ, Gavin CE, Aschner M, Gunter TE (2013) Manganese neurotoxicity and the role of reactive oxygen species. Free Radic Biol Med 62:65–75

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mason LH, Harp JP, Han DY (2014) Pb neurotoxicity: neuropsychological effects of lead toxicity. Biomed Res Int 2014:840547

    PubMed  PubMed Central  Google Scholar 

  • Messner B, Turkcan A, Ploner C, Laufer G, Bernhard D (2015) Cadmium overkill: autophagy, apoptosis and necrosis signalling in endothelial cells exposed to cadmium. Cell Mol Life Sci 73(8):1699–1713

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Needleman HL (2000) The removal of lead from gasoline: historical and personal reflections. Environ Res 84:20–35

    Article  CAS  PubMed  Google Scholar 

  • Nikolov Z (1974) Hearing reduction caused by manganese and noise. JFORL J Fr Otorhinolaryngol Audiophonol Chir Maxillofac 23:231–234

    CAS  PubMed  Google Scholar 

  • Nogawa K, Yamada Y, Honda R, Ishizaki M, Tsuritani I, Kawano S et al (1983) The relationship between itai-itai disease among inhabitants of the Jinzu River basin and cadmium in rice. Toxicol Lett 17:263–266

    Article  CAS  PubMed  Google Scholar 

  • Olanow CW, Good PF, Shinotoh H, Hewitt KA, Vingerhoets F, Snow BJ et al (1996) Manganese intoxication in the rhesus monkey: a clinical, imaging, pathologic, and biochemical study. Neurology 46:492–498

    Article  CAS  PubMed  Google Scholar 

  • Oldenburg M, Wegner R, Baur X (2009) Severe cobalt intoxication due to prosthesis wear in repeated total hip arthroplasty. J Arthroplasty 24(825):e15–e20

    PubMed  Google Scholar 

  • Orent ER, McCollum EV (1931) Effects of deprivation of manganese in the rat. J Biol Chem 92:661–678

    Google Scholar 

  • Osman K, Pawlas K, Schutz A, Gazdzik M, Sokal JA, Vahter M (1999) Lead exposure and hearing effects in children in Katowice, Poland. Environ Res 80:1–8

    Article  CAS  PubMed  Google Scholar 

  • Otto DA, Fox DA (1993) Auditory and visual dysfunction following lead exposure. Neurotoxicology 14:191–207

    CAS  PubMed  Google Scholar 

  • Ozcaglar HU, Agirdir B, Dinc O, Turhan M, Kilincarslan S, Oner G (2001) Effects of cadmium on the hearing system. Acta Otolaryngol 121:393–397

    Article  CAS  PubMed  Google Scholar 

  • Pal PK, Samii A, Calne DB (1999) Manganese neurotoxicity: a review of clinical features, imaging and pathology. Neurotoxicology 20:227–238

    CAS  PubMed  Google Scholar 

  • Pande M, Flora SJ (2002) Lead induced oxidative damage and its response to combined administration of alpha-lipoic acid and succimers in rats. Toxicology 177:187–196

    Article  CAS  PubMed  Google Scholar 

  • Park RM, Bowler RM, Eggerth DE, Diamond E, Spencer KJ, Smith D et al (2006) Issues in neurological risk assessment for occupational exposures: the Bay Bridge welders. Neurotoxicology 27:373–384

    Article  CAS  PubMed  Google Scholar 

  • Paustenbach DJ, Tvermoes BE, Unice KM, Finley BL, Kerger BD (2013) A review of the health hazards posed by cobalt. Crit Rev Toxicol 43:316–362

    Article  CAS  PubMed  Google Scholar 

  • Pelclova D, Sklensky M, Janicek P, Lach K (2012) Severe cobalt intoxication following hip replacement revision: clinical features and outcome. Clin Toxicol (Phila) 50:262–265

    Article  CAS  Google Scholar 

  • Permenter MG, Dennis WE, Sutto TE, Jackson DA, Lewis JA, Stallings JD (2013) Exposure to cobalt causes transcriptomic and proteomic changes in two rat liver derived cell lines. PLoS ONE 8:e83751

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Petit A, Mwale F, Zukor DJ, Catelas I, Antoniou J, Huk OL (2004) Effect of cobalt and chromium ions on bcl-2, bax, caspase-3, and caspase-8 expression in human U937 macrophages. Biomaterials 25:2013–2018

    Article  CAS  PubMed  Google Scholar 

  • Pinilla-Tenas JJ, Sparkman BK, Shawki A, Illing AC, Mitchell CJ, Zhao N et al (2011) Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. Am J Physiol Cell Physiol 301:C862–C871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pizon AF, Abesamis M, King AM, Menke N (2013) Prosthetic hip-associated cobalt toxicity. J Med Toxicol 9:416–417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pomier-Layrargues G, Spahr L, Butterworth RF (1995) Increased manganese concentrations in pallidum of cirrhotic patients. Lancet 345:735

    Article  CAS  PubMed  Google Scholar 

  • Prasher D (2009) Heavy metals and noise exposure: health effects. Noise Health 11:141–144

    Article  PubMed  Google Scholar 

  • Prozialeck WC, Edwards JR, Vaidya VS, Bonventre JV (2009) Preclinical evaluation of novel urinary biomarkers of cadmium nephrotoxicity. Toxicol Appl Pharmacol 238:301–305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qi W, Ding D, Salvi RJ (2008) Cytotoxic effects of dimethyl sulphoxide (DMSO) on cochlear organotypic cultures. Hear Res 236:52–60

    Article  CAS  PubMed  Google Scholar 

  • Qi W, Ding D, Zhu H, Lu D, Wang Y, Ding J et al (2014) Efficient siRNA transfection to the inner ear through the intact round window by a novel proteidic delivery technology in the chinchilla. Gene Ther 21:10–18

    Article  CAS  PubMed  Google Scholar 

  • Quadri M, Federico A, Zhao T, Breedveld GJ, Battisti C, Delnooz C et al (2012) Mutations in SLC30A10 cause Parkinsonism and dystonia with hypermanganesemia, polycythemia, and chronic liver disease. Am J Hum Genet 90:467–477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rabenstein DL, Isab AA (1982) A proton nuclear magnetic resonance study of the interaction of mercury with intact human erythrocytes. Biochim Biophys Acta 721:374–384

    Article  CAS  PubMed  Google Scholar 

  • Rafati-Rahimzadeh M, Rafati-Rahimzadeh M, Kazemi S, Moghadamnia AA (2014) Current approaches of the management of mercury poisoning: need of the hour. Daru 22:46

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rehfisch P, Anderson M, Berg P, Lampa E, Nordling Y, Svartengren M et al (2012) Lung function and respiratory symptoms in hard metal workers exposed to cobalt. J Occup Environ Med 54:409–413

    Article  CAS  PubMed  Google Scholar 

  • Rice KM, Walker EM Jr, Wu M, Gillette C, Blough ER (2014) Environmental mercury and its toxic effects. J Prev Med Public Health 47:74–83

    Article  PubMed  PubMed Central  Google Scholar 

  • Rigon AP, Cordova FM, Oliveira CS, Posser T, Costa AP, Silva IG et al (2008) Neurotoxicity of cadmium on immature hippocampus and a neuroprotective role for p38 MAPK. Neurotoxicology 29:727–734

    Article  CAS  PubMed  Google Scholar 

  • Roth JA (2006) Homeostatic and toxic mechanisms regulating manganese uptake, retention, and elimination. Biol Res 39:45–57

    Article  CAS  PubMed  Google Scholar 

  • Roth JA, Feng L, Walowitz J, Browne RW (2000) Manganese-induced rat pheochromocytoma (PC12) cell death is independent of caspase activation. J Neurosci Res 61:162–171

    Article  CAS  PubMed  Google Scholar 

  • Roth JA, Horbinski C, Higgins D, Lein P, Garrick MD (2002) Mechanisms of manganese-induced rat pheochromocytoma (PC12) cell death and cell differentiation. Neurotoxicology 23:147–157

    Article  CAS  PubMed  Google Scholar 

  • Roth J, Ponzoni S, Aschner M (2013) Manganese homeostasis and transport. Met Ions Life Sci 12:169–201

    Article  PubMed  Google Scholar 

  • Rovetta F, Stacchiotti A, Faggi F, Catalani S, Apostoli P, Fanzani A et al (2013) Cobalt triggers necrotic cell death and atrophy in skeletal C2C12 myotubes. Toxicol Appl Pharmacol 271:196–205

    Article  CAS  PubMed  Google Scholar 

  • Ruel J, Chen C, Pujol R, Bobbin RP, Puel JL (1999) AMPA-preferring glutamate receptors in cochlear physiology of adult guinea-pig. J Physiol 518(Pt 3):667–680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sallmen M (2001) Exposure to lead and male fertility. Int J Occup Med Environ Health 14:219–222

    CAS  PubMed  Google Scholar 

  • Salvi R, Lobarinas E, Sun W (2009) Overview of anatomy and physiology of the peripheral auditory system. In: Chaisin M (ed) Hearing loss and musicians: prevention and management. Plural Publishers, San Diego, pp 11–29

    Google Scholar 

  • Sanders T, Liu Y, Buchner V, Tchounwou PB (2009) Neurotoxic effects and biomarkers of lead exposure: a review. Rev Environ Health 24:15–45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santamaria AB, Sulsky SI (2010) Risk assessment of an essential element: manganese. J Toxicol Environ Health A 73:128–155

    Article  CAS  PubMed  Google Scholar 

  • Saric M, Piasek M (2000) Environmental exposure to manganese and combined exposure to gaseous upper respiratory irritants: mechanism of action and adverse health effects. Rev Environ Health 15:413–419

    Article  CAS  PubMed  Google Scholar 

  • Sarkar A, Bhagat J, Ingole BS, Rao DP, Markad VL (2015) Genotoxicity of cadmium chloride in the marine gastropod Nerita chamaeleon using comet assay and alkaline unwinding assay. Environ Toxicol 30:177–187

    Article  CAS  PubMed  Google Scholar 

  • Scharf B, Clement CC, Zolla V, Perino G, Yan B, Elci SG et al (2014) Molecular analysis of chromium and cobalt-related toxicity. Sci Rep 4:5729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schaumberg DA, Mendes F, Balaram M, Dana MR, Sparrow D, Hu H (2004) Accumulated lead exposure and risk of age-related cataract in men. JAMA 292:2750–2754

    Article  CAS  PubMed  Google Scholar 

  • Schmutzhard J, Kositz CH, Glueckert R, Schmutzhard E, Schrott-Fischer A, Lackner P (2012) Apoptosis of the fibrocytes type 1 in the spiral ligament and blood labyrinth barrier disturbance cause hearing impairment in murine cerebral malaria. Malar J 11:30

    Article  PubMed  PubMed Central  Google Scholar 

  • Schrantz N, Blanchard DA, Mitenne F, Auffredou MT, Vazquez A, Leca G (1999) Manganese induces apoptosis of human B cells: caspase-dependent cell death blocked by bcl-2. Cell Death Differ 6:445–453

    Article  CAS  PubMed  Google Scholar 

  • Schwartz J, Otto D (1987) Blood lead, hearing thresholds, and neurobehavioral development in children and youth. Arch Environ Health 42:153–160

    Article  CAS  PubMed  Google Scholar 

  • Seghizzi P, D’Adda F, Borleri D, Barbic F, Mosconi G (1994) Cobalt myocardiopathy. A critical review of literature. Sci Total Environ 150:105–109

    Article  CAS  PubMed  Google Scholar 

  • Shi LZ, Zheng W (2007) Early lead exposure increases the leakage of the blood–cerebrospinal fluid barrier, in vitro. Hum Exp Toxicol 26:159–167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simonsen LO, Brown AM, Harbak H, Kristensen BI, Bennekou P (2011) Cobalt uptake and binding in human red blood cells. Blood Cells Mol Dis 46:266–276

    Article  CAS  PubMed  Google Scholar 

  • Simonsen LO, Harbak H, Bennekou P (2012) Cobalt metabolism and toxicology—a brief update. Sci Total Environ 432:210–215

    Article  CAS  PubMed  Google Scholar 

  • Sousa CA, Soares EV (2014) Mitochondria are the main source and one of the targets of Pb (lead)-induced oxidative stress in the yeast Saccharomyces cerevisiae. Appl Microbiol Biotechnol 98:5153–5160

    Article  CAS  PubMed  Google Scholar 

  • Staudinger KC, Roth VS (1998) Occupational lead poisoning. Am Fam Physician 57(719–26):31–32

    Google Scholar 

  • Strause LG, Hegenauer J, Saltman P, Cone R, Resnick D (1986) Effects of long-term dietary manganese and copper deficiency on rat skeleton. J Nutr 116:135–141

    CAS  PubMed  Google Scholar 

  • Sutto TE (2011) Prioritization of the oral (ingestive) hazard of industrial chemicals. Prioritization of the oral (ingestive) hazard of industrial chemicals. Naval Research Laboratory, Washington, DC

    Google Scholar 

  • Swennen B, Buchet JP, Stanescu D, Lison D, Lauwerys R (1993) Epidemiological survey of workers exposed to cobalt oxides, cobalt salts, and cobalt metal. Br J Ind Med 50:835–842

    CAS  PubMed  PubMed Central  Google Scholar 

  • Syversen T, Kaur P (2012) The toxicology of mercury and its compounds. J Trace Elem Med Biol 26:215–226

    Article  CAS  PubMed  Google Scholar 

  • Tuschl K, Clayton PT, Gospe SM Jr, Gulab S, Ibrahim S, Singhi P et al (2012) Syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by mutations in SLC30A10, a manganese transporter in man. Am J Hum Genet 90:457–466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vaziri ND, Gonick HC (2008) Cardiovascular effects of lead exposure. Indian J Med Res 128:426–435

    CAS  PubMed  Google Scholar 

  • Vazquez M, Velez D, Devesa V, Puig S (2015) Participation of divalent cation transporter DMT1 in the uptake of inorganic mercury. Toxicology 331:119–124

    Article  CAS  PubMed  Google Scholar 

  • Vergilio CS, Carvalho CE, Melo EJ (2015) Mercury-induced dysfunctions in multiple organelles leading to cell death. Toxicol In Vitro 29:63–71

    Article  CAS  PubMed  Google Scholar 

  • Viaene MK, Roels HA, Leenders J, De Groof M, Swerts LJ, Lison D et al (1999) Cadmium: a possible etiological factor in peripheral polyneuropathy. Neurotoxicology 20:7–16

    CAS  PubMed  Google Scholar 

  • Viaene MK, Masschelein R, Leenders J, De Groof M, Swerts LJ, Roels HA (2000) Neurobehavioural effects of occupational exposure to cadmium: a cross sectional epidemiological study. Occup Environ Med 57:19–27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang SH, Shih YL, Ko WC, Wei YH, Shih CM (2008) Cadmium-induced autophagy and apoptosis are mediated by a calcium signaling pathway. Cell Mol Life Sci 65:3640–3652

    Article  CAS  PubMed  Google Scholar 

  • Wang Q, Luo W, Zhang W, Liu M, Song H, Chen J (2011) Involvement of DMT1 + IRE in the transport of lead in an in vitro BBB model. Toxicol In Vitro 25:991–998

    Article  CAS  PubMed  Google Scholar 

  • Wang CY, Jenkitkasemwong S, Duarte S, Sparkman BK, Shawki A, Mackenzie B et al (2012) ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. J Biol Chem 287:34032–34043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watrach AM (1964) Degeneration of mitochondria in lead poisoning. J Ultrastruct Res 10:177–181

    Article  CAS  PubMed  Google Scholar 

  • Weisskopf MG, Proctor SP, Wright RO, Schwartz J, Spiro A 3rd, Sparrow D et al (2007) Cumulative lead exposure and cognitive performance among elderly men. Epidemiology 18:59–66

    Article  PubMed  Google Scholar 

  • Whitworth CA, Hudson TE, Rybak LP (1999) The effect of combined administration of cadmium and furosemide on auditory function in the rat. Hear Res 129:61–70

    Article  CAS  PubMed  Google Scholar 

  • Xu C, Johnson JE, Singh PK, Jones MM, Yan H, Carter CE (1996) In vivo studies of cadmium-induced apoptosis in testicular tissue of the rat and its modulation by a chelating agent. Toxicology 107:1–8

    Article  CAS  PubMed  Google Scholar 

  • Xue-wen W, Ding D, Hong S, Hong L, Hai-yan J, Salvi R (2011) Lead neurotoxicity in rat cochlear organotypic cultures. J Otol 6(2):45–50

    Google Scholar 

  • Yamada K (2013) Cobalt: its role in health and disease. Met Ions Life Sci 13:295–320

    Article  PubMed  Google Scholar 

  • Yamamura K, Terayama K, Yamamoto N, Kohyama A, Kishi R (1989) Effects of acute lead acetate exposure on adult guinea pigs: electrophysiological study of the inner ear. Fundam Appl Toxicol 13:509–515

    Article  CAS  PubMed  Google Scholar 

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Research supported in part by grants from NIOSH R01 OH010235.

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Roth, J.A., Salvi, R. Ototoxicity of Divalent Metals. Neurotox Res 30, 268–282 (2016). https://doi.org/10.1007/s12640-016-9627-3

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