Skip to main content

Advertisement

Log in

Cadmium-Induced Ototoxicity in Rat Cochlear Organotypic Cultures

  • Original Article
  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

Cadmium (Cd), a widely used industrial metal, is extremely nephrotoxic and neurotoxic; however, its effects on the peripheral auditory system are poorly understood. To evaluate the ototoxicity of Cd, we treated cochlear organotypic cultures from postnatal day 3 rats with Cd concentrations from 10 to 500 μM for 24 or 48 h. Afterward, we evaluated the degree of damage to hair cells, auditory nerve fibers, and spiral ganglion neurons. Damage to the hair cells, auditory nerve fibers, and spiral ganglion neurons systematically increased in a dose and time-dependent manner. Exposure to Cd concentrations of 10 μM for 24 and 48 h resulted in minor inner and outer hair cell loss in the basal third of the cochlea. As Cd concentrations increased, toxicity spread toward the apex, also in a time-dependent manner. Treatment with 100 μM Cd for 48 h resulted in substantial (>30 %) hair cell loss over the entire cochlea. Cd was also toxic to auditory nerve fibers and spiral ganglion neurons; 100 μM of Cd for 24 h or 10 μM of Cd for 48 h resulted in considerable damage to auditory nerve fibers and spiral ganglion neurons. These findings are the first to demonstrate that Cd can cause significant lesions to peripheral auditory nerve fibers, spiral ganglion neurons, and sensory hair cells in organotypic cultures from postnatal cochleae.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • 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

    CAS  PubMed  Google Scholar 

  • Alagramam KN, Goodyear RJ, Geng R, Furness DN, van Aken AF, Marcotti W et al (2011) Mutations in protocadherin 15 and cadherin 23 affect tip links and mechanotransduction in Mammalian sensory hair cells. PLoS ONE 6:e19183

    CAS  PubMed  PubMed Central  Google Scholar 

  • Almar MM, Diaz-Mayans J, Romero FJ (1987) Glutathione content and GSH S-transferase activity in midgut gland of Procambarus clarkii. Sex differences, the effect of fasting, and their implications in cadmium toxicity. Comp Biochem Physiol C 87:433–435

    CAS  PubMed  Google Scholar 

  • Antonio MT, Corredor L, Leret ML (2003) Study of the activity of several brain enzymes like markers of the neurotoxicity induced by perinatal exposure to lead and/or cadmium. Toxicol Lett 143:331–340

    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

    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

    CAS  PubMed  Google Scholar 

  • Bianucci E, Fabra A, Castro S (2011) Involvement of glutathione and enzymatic defense system against cadmium toxicity in Bradyrhizobium sp. strains (peanut symbionts). Biometals 25:23

    PubMed  Google Scholar 

  • Cartana J, Romeu A, Arola L (1992) Effects of copper, cadmium and nickel on liver and kidney glutathione redox cycle of rats (Rattus sp.). Comp Biochem Physiol C 101:209–213

    CAS  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

    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

    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

    CAS  PubMed  Google Scholar 

  • Chuang SM, Wang IC, Yang JL (2000) Roles of JNK, p38 and ERK mitogen-activated protein kinases in the growth inhibition and apoptosis induced by cadmium. Carcinogenesis 21:1423–1432

    CAS  PubMed  Google Scholar 

  • Cookson MR, Pentreath VW (1996) Protective roles of glutathione in the toxicity of mercury and cadmium compounds to C6 glioma cells. Toxicol In Vitro 10:257–264

    CAS  PubMed  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

    CAS  PubMed  Google Scholar 

  • Dickel H, Kuss O, Schmidt A, Diepgen TL (2002) Occupational relevance of positive standard patch-test results in employed persons with an initial report of an occupational skin disease. Int Arch Occup Environ Health 75:423–434

    CAS  PubMed  Google Scholar 

  • Ding D, Salvi R (2004) Review of cellular changes in the cochlea due to aminoglycoside antibiotics. Volta Rev 105:407–438

    Google Scholar 

  • Ding D, Salvi R (2007) Experiences in ototoxic investigations in aminoglycoside antibiotics. Chin J Otol 5:125–131

    Google Scholar 

  • Ding D, Stracher A, Salvi RJ (2002) Leupeptin protects cochlear and vestibular hair cells from gentamicin ototoxicity. Hear Res 164:115–126

    CAS  PubMed  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

    CAS  PubMed  Google Scholar 

  • Ding D, Qi W, Yu D, Jiang H, Salvi R (2009a) Ototoxic effects of mefloquine in cochlear organotypic cultures. J Otol 4:29–38

    Google Scholar 

  • Ding D, Wang P, Jiang H, Coling D, Salvi R (2009b) Gene expression in cisplatin ototoxicity and protection with p53 inhibitor. J Otol 4:15–24

    Google Scholar 

  • Ding D, Jiang H, Salvi RJ (2010) Mechanisms of rapid sensory hair-cell death following co-administration of gentamicin and ethacrynic acid. Hear Res 259:16–23

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ding D, He J, Allman BL, Yu D, Jiang H, Seigel GM et al (2011a) Cisplatin ototoxicity in rat cochlear organotypic cultures. Hear Res 282:196–203

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dong S, Shen HM, Ong CN (2001) Cadmium-induced apoptosis and phenotypic changes in mouse thymocytes. Mol Cell Biochem 222:11–20

    CAS  PubMed  Google Scholar 

  • El-Naggar AH, El-Sheekh MM (1998) Abolishing cadmium toxicity in Chlorella vulgaris by ascorbic acid, calcium, glucose and reduced glutathione. Environ Pollut 101:169–174

    CAS  PubMed  Google Scholar 

  • Fern R, Black JA, Ransom BR, Waxman SG (1996) Cd(2+)-induced injury in CNS white matter. J Neurophysiol 76:3264–3273

    CAS  PubMed  Google Scholar 

  • Fernandez EL, Gustafson AL, Andersson M, Hellman B, Dencker L (2003) Cadmium-induced changes in apoptotic gene expression levels and DNA damage in mouse embryos are blocked by zinc. Toxicol Sci 76:162–170

    CAS  PubMed  Google Scholar 

  • Friberg L (1983) Cadmium. Annu Rev Public Health 4:367–373

    CAS  PubMed  Google Scholar 

  • Galan A, Garcia-Bermejo ML, Troyano A, Vilaboa NE, de Blas E, Kazanietz MG et al (2000) Stimulation of p38 mitogen-activated protein kinase is an early regulatory event for the cadmium-induced apoptosis in human promonocytic cells. J Biol Chem 275:11418–11424

    CAS  PubMed  Google Scholar 

  • Godt J, Scheidig F, Grosse-Siestrup C, Esche V, Brandenburg P, Reich A et al (2006) The toxicity of cadmium and resulting hazards for human health. J Occup Med Toxicol 1:22

    PubMed  PubMed Central  Google Scholar 

  • Goering PL, Klaassen CD (1983) Altered subcellular distribution of cadmium following cadmium pretreatment: possible mechanism of tolerance to cadmium-induced lethality. Toxicol Appl Pharmacol 70:195–203

    CAS  PubMed  Google Scholar 

  • Hamada T, Nakano S, Iwai S, Tanimoto A, Ariyoshi K, Koide O (1991) Pathological study on beagles after long-term oral administration of cadmium. Toxicol Pathol 19:138–47.

    Google Scholar 

  • Hart RP, Rose CS, Hamer RM (1989) Neuropsychological effects of occupational exposure to cadmium. J Clin Exp Neuropsychol 11:933–943

    CAS  PubMed  Google Scholar 

  • Helbig K, Grosse C, Nies DH (2008) Cadmium toxicity in glutathione mutants of Escherichia coli. J Bacteriol 190:5439–5454

    CAS  PubMed  PubMed Central  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 

  • 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

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hughes J, Gobe G (2007) Identification and quantification of apoptosis in the kidney using morphology, biochemical and molecular markers. Nephrology (Carlton) 12:452–458

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Inaba T, Kobayashi E, Suwazono Y, Uetani M, Oishi M, Nakagawa H et al (2005) Estimation of cumulative cadmium intake causing Itai–itai disease. Toxicol Lett 159:192–201

    CAS  PubMed  Google Scholar 

  • Joseph P (2009) Mechanisms of cadmium carcinogenesis. Toxicol Appl Pharmacol 238:272–279

    CAS  PubMed  Google Scholar 

  • Jung YS, Jeong EM, Park EK, Kim YM, Sohn S, Lee SH et al (2008) Cadmium induces apoptotic cell death through p38 MAPK in brain microvessel endothelial cells. Eur J Pharmacol 578:11–18

    CAS  PubMed  Google Scholar 

  • Kane KL, Longo-Guess CM, Gagnon LH, Ding D, Salvi RJ, Johnson KR (2012) Genetic background effects on age-related hearing loss associated with Cdh23 variants in mice. Hear Res 283:80–88

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kang YJ (1992) Exogenous glutathione decreases cellular cadmium uptake and toxicity. Drug Metab Dispos 20:714–718

    CAS  PubMed  Google Scholar 

  • Kazmierczak P, Sakaguchi H, Tokita J, Wilson-Kubalek EM, Milligan RA, Muller U et al (2007) Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells. Nature 449:87–91

    CAS  PubMed  Google Scholar 

  • Kim MS, Kim BJ, Woo HN, Kim KW, Kim KB, Kim IK et al (2000) Cadmium induces caspase-mediated cell death: suppression by Bcl-2. Toxicology 145:27–37

    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

    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

    CAS  PubMed  Google Scholar 

  • Kim K, Fujimoto VY, Parsons PJ, Steuerwald AJ, Browne RW, Bloom MS (2010) Recent cadmium exposure among male partners may affect oocyte fertilization during in vitro fertilization (IVF). J Assist Reprod Genet 27:463–468

    PubMed  PubMed Central  Google Scholar 

  • Klaassen CD, Wong KL (1982) Cadmium toxicity in the newborn rat. Can J Physiol Pharmacol 60:1027–1036

    CAS  PubMed  Google Scholar 

  • Kobayashi E, Suwazono Y, Dochi M, Honda R, Kido T, Nakagawa H (2009) Influence of drinking and/or cooking with Jinzu River water on the development of Itai–itai disease. Biol Trace Elem Res 129:46–57

    CAS  PubMed  Google Scholar 

  • Kondoh M, Araragi S, Sato K, Higashimoto M, Takiguchi M, Sato M (2002) Cadmium induces apoptosis partly via caspase-9 activation in HL-60 cells. Toxicology 170:111–117

    CAS  PubMed  Google Scholar 

  • Kumar R, Agarwal AK, Seth PK (1996) Oxidative stress-mediated neurotoxicity of cadmium. Toxicol Lett 89:65–69

    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

    CAS  PubMed  Google Scholar 

  • Leoni G, Bogliolo L, Deiana G, Berlinguer F, Rosati I, Pintus PP et al (2002) Influence of cadmium exposure on in vitro ovine gamete dysfunction. Reprod Toxicol 16:371–377

    CAS  PubMed  Google Scholar 

  • Li M, Xia T, Jiang CS, Li LJ, Fu JL, Zhou ZC (2003) Cadmium directly induced the opening of membrane permeability pore of mitochondria which possibly involved in cadmium-triggered apoptosis. Toxicology 194:19–33

    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

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu S, Li S, Zhu H, Cheng S, Zheng QY (2012) A mutation in the cdh23 gene causes age-related hearing loss in Cdh23(nmf308/nmf308) mice. Gene 499:309–317

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lopez E, Figueroa S, Oset-Gasque MJ, Gonzalez MP (2003) Apoptosis and necrosis: two distinct events induced by cadmium in cortical neurons in culture. Br J Pharmacol 138:901–911

    CAS  PubMed  PubMed Central  Google Scholar 

  • Loza-Coll MA, Perera S, Shi W, Filmus J (2005) A transient increase in the activity of Src-family kinases induced by cell detachment delays anoikis of intestinal epithelial cells. Oncogene 24:1727–1737

    CAS  PubMed  Google Scholar 

  • MacKinnon Y, Kapron CM (2010) Reduction in cadmium-induced toxicity and c-Jun N-terminal kinase activation by glutathione in cultured mouse embryonic cells. Birth Defects Res A Clin Mol Teratol 88:707–714

    CAS  PubMed  Google Scholar 

  • Mao WP, Ye JL, Guan ZB, Zhao JM, Zhang C, Zhang NN et al (2007) Cadmium induces apoptosis in human embryonic kidney (HEK) 293 cells by caspase-dependent and -independent pathways acting on mitochondria. Toxicol In Vitro 21:343–354

    CAS  PubMed  Google Scholar 

  • Massadeh AM, Alali FQ, Jaradat QM (2005) Determination of cadmium and lead in different cigarette brands in Jordan. Environ Monit Assess 104:163–170

    CAS  PubMed  Google Scholar 

  • Muller L (1986) Consequences of cadmium toxicity in rat hepatocytes: effects of cadmium on the glutathione-peroxidase system. Toxicol Lett 30:259–265

    CAS  PubMed  Google Scholar 

  • National Center for Health Statistics (1988). Data from the National Health Interview Survey

  • Nemery B (1990) Metal toxicity and the respiratory tract. Eur Respir J 3:202–219

    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

    CAS  PubMed  Google Scholar 

  • Nordberg G, Jin T, Wu X, Lu J, Chen L, Liang Y et al (2012) Kidney dysfunction and cadmium exposure-factors influencing dose-response relationships. J Trace Elem Med Biol 26:197–200

    CAS  PubMed  Google Scholar 

  • O'Callaghan JP, Miller DB (1986) Diethyldithiocarbamate increases distribution of cadmium to brain but prevents cadmium-induced neurotoxicity. Brain Res 370:354–358

    PubMed  Google Scholar 

  • Ochi T, Otsuka F, Takahashi K, Ohsawa M (1988) Glutathione and metallothioneins as cellular defense against cadmium toxicity in cultured Chinese hamster cells. Chem Biol Interact 65:1–14

    CAS  PubMed  Google Scholar 

  • Okuda B, Iwamoto Y, Tachibana H, Sugita M (1997) Parkinsonism after acute cadmium poisoning. Clin Neurol Neurosurg 99:263–265

    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

    CAS  PubMed  Google Scholar 

  • Pathak N, Khandelwal S (2006) Modulation of cadmium induced alterations in murine thymocytes by piperine: oxidative stress, apoptosis, phenotyping and blastogenesis. Biochem Pharmacol 72:486–497

    CAS  PubMed  Google Scholar 

  • Poliandri AH, Cabilla JP, Velardez MO, Bodo CC, Duvilanski BH (2003) Cadmium induces apoptosis in anterior pituitary cells that can be reversed by treatment with antioxidants. Toxicol Appl Pharmacol 190:17–24

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Prins JM, Brooks DM, Thompson CM, Lurie DI (2010) Chronic low-level Pb exposure during development decreases the expression of the voltage-dependent anion channel in auditory neurons of the brainstem. Neurotoxicology 31:662–673

    CAS  PubMed  PubMed Central  Google Scholar 

  • Prozialeck WC (2000) Evidence that E-cadherin may be a target for cadmium toxicity in epithelial cells. Toxicol Appl Pharmacol 164:231–249

    CAS  PubMed  Google Scholar 

  • Prozialeck WC, Lamar PC (1997) Cadmium (Cd2+) disrupts E-cadherin-dependent cell–cell junctions in MDCK cells. In Vitro Cell Dev Biol Anim 33:516–526

    CAS  PubMed  Google Scholar 

  • Prozialeck WC, Niewenhuis RJ (1991) Cadmium (Cd2+) disrupts intercellular junctions and actin filaments in LLC-PK1 cells. Toxicol Appl Pharmacol 107:81–97

    CAS  PubMed  Google Scholar 

  • Prozialeck WC, Lamar PC, Lynch SM (2003) Cadmium alters the localization of N-cadherin, E-cadherin, and beta-catenin in the proximal tubule epithelium. Toxicol Appl Pharmacol 189:180–195

    CAS  PubMed  Google Scholar 

  • Prozialeck WC, Vaidya VS, Liu J, Waalkes MP, Edwards JR, Lamar PC et al (2007) Kidney injury molecule-1 is an early biomarker of cadmium nephrotoxicity. Kidney Int 72:985–993

    CAS  PubMed  PubMed Central  Google Scholar 

  • Prozialeck WC, Edwards JR, Lamar PC, Liu J, Vaidya VS, Bonventre JV (2009) Expression of kidney injury molecule-1 (Kim-1) in relation to necrosis and apoptosis during the early stages of Cd-induced proximal tubule injury. Toxicol Appl Pharmacol 238:306–314

    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

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rai LC, Jensen TE, Rachlin JW (1990) A morphometric and X-ray energy dispersive approach to monitoring pH-altered cadmium toxicity in Anabaena flos-aquae. Arch Environ Contam Toxicol 19:479–487

    CAS  PubMed  Google Scholar 

  • Reeves PG, Rossow KL (1996) Zinc-and/or cadmium-induced intestinal metallothionein and copper metabolism in adult rats. NutrBiochem 7:128–134

    CAS  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

    CAS  PubMed  Google Scholar 

  • Sansanwal P, Yen B, Gahl WA, Ma Y, Ying L, Wong LJ et al (2010) Mitochondrial autophagy promotes cellular injury in nephropathic cystinosis. J Am Soc Nephrol 21:272–283

    CAS  PubMed  PubMed Central  Google Scholar 

  • Schmid BP, Hall JL, Goulding E, Fabro S, Dixon R (1983) In vitro exposure of male and female mice gametes to cadmium chloride during the fertilization process, and its effects on pregnancy outcome. Toxicol Appl Pharmacol 69:326–332

    CAS  PubMed  Google Scholar 

  • Shih CM, Ko WC, Wu JS, Wei YH, Wang LF, Chang EE et al (2004) Mediating of caspase-independent apoptosis by cadmium through the mitochondria-ROS pathway in MRC-5 fibroblasts. J Cell Biochem 91:384–397

    CAS  PubMed  Google Scholar 

  • Shimizu M, Morita S (1990) Effects of fasting on cadmium toxicity, glutathione metabolism, and metallothionein synthesis in rats. Toxicol Appl Pharmacol 103:28–39

    CAS  PubMed  Google Scholar 

  • Singhal RK, Anderson ME, Meister A (1987) Glutathione, a first line of defense against cadmium toxicity. FASEB J 1:220–223

    CAS  PubMed  Google Scholar 

  • Sullivan MF, Miller BM, Goebel JC (1984) Gastrointestinal absorption of metals (51Cr, 65Zn, 95mTc, 109Cd, 113Sn, 147Pm, and 238Pu) by rats and swine. Environ Res 35:439–453

    CAS  PubMed  Google Scholar 

  • Sura P, Ristic N, Bronowicka P, Wrobel M (2006) Cadmium toxicity related to cysteine metabolism and glutathione levels in frog Rana ridibunda tissues. Comp Biochem Physiol C 142:128–135

    Google Scholar 

  • Swiergosz-Kowalewska R (2001) Cadmium distribution and toxicity in tissues of small rodents. Microsc Res Tech 55:208–222

    CAS  PubMed  Google Scholar 

  • Tsuchiya K (1976) Epidemiological studies on cadmium in the environment in Japan: etiology of itai–itai disease. Fed Proc 35:2412–2418

    CAS  PubMed  Google Scholar 

  • Tynecka Z, Malm A, Kosikowska U, Kot A (1998) Substrate-dependent cadmium toxicity affecting energy-linked K+/86Rb transport in Staphylococcus aureus. Folia Microbiol (Praha) 43:617–622

    CAS  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

    CAS  PubMed  PubMed Central  Google Scholar 

  • Walker EM Jr, Fazekas-May MA, Bowen WR (1990) Nephrotoxic and ototoxic agents. Clin Lab Med 10:323–354

    CAS  PubMed  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

    CAS  PubMed  Google Scholar 

  • Waters MD, Gardner DE, Aranyi C, Coffin DL (1975) Metal toxicity for rabbit alveolar macrophages in vitro. Environ Res 9:32–47

    CAS  PubMed  Google Scholar 

  • Webster WS, Valois AA (1981) The toxic effects of cadmium on the neonatal mouse CNS. J Neuropathol Exp Neurol 40:247–257

    CAS  PubMed  Google Scholar 

  • Wei L, Ding D, Salvi R (2010) Salicylate-induced degeneration of cochlea spiral ganglion neurons-apoptosis signaling. Neuroscience 168:288–299

    CAS  PubMed  PubMed Central  Google Scholar 

  • Weng Z, Xin M, Pablo L, Grueneberg D, Hagel M, Bain G et al (2002) Protection against anoikis and down-regulation of cadherin expression by a regulatable beta-catenin protein. J Biol Chem 277:18677–18686

    CAS  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

    CAS  PubMed  Google Scholar 

  • Wong KL, Klaassen CD (1982) Neurotoxic effects of cadmium in young rats. Toxicol Appl Pharmacol 63:330–337

    CAS  PubMed  Google Scholar 

  • Wu X, Ding D, Sun H, Liu H, Jiang H, Salvi R (2011a) Lead neurotoxicity in rat cochlear organotypic cultures. J Otology 6:45–52

    Google Scholar 

  • Wu X, Ding D, Sun H, Liu H, Jiang H, Salvi R (2011b) Lead neurotoxicity in rat cochlear organotypic cultures. Chin J Otol 6:44–49

    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

    CAS  PubMed  Google Scholar 

  • Yang MS, Yu LC, Pat SW (2007) Manipulation of energy and redox states in the C6 glioma cells by buthionine sulfoxamine and N-acetylcysteine and the effect on cell survival to cadmium toxicity. Cell Mol Biol (Noisy-le-grand) 53:56–61

    CAS  Google Scholar 

  • Yu D, Ding D, Jiang H, Stolzberg D, Salvi R (2011) Mefloquine damage vestibular hair cells in organotypic cultures. Neurotox Res 20:51–58

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

Research supported in part by grants from NIH (R01DC009091 and R01DC009219) and NIOSH (R01 OH010235).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Richard Salvi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, H., Ding, D., Sun, H. et al. Cadmium-Induced Ototoxicity in Rat Cochlear Organotypic Cultures. Neurotox Res 26, 179–189 (2014). https://doi.org/10.1007/s12640-014-9461-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12640-014-9461-4

Keywords

Navigation