Toxicology of Cadmium and Its Damage to Mammalian Organs

  • Frank ThévenodEmail author
  • Wing-Kee Lee
Part of the Metal Ions in Life Sciences book series (MILS, volume 11)


The detrimental health effects of cadmium (Cd) were first described in the mid 19th century. As part of industrial developments, increasing usage of Cd has led to widespread contamination of the environment that threatens human health, particularly today. Rather than acute, lethal exposures, the real challenge in the 21st century in a global setting seems to be chronic low Cd exposure (CLCE), mainly from dietary sources. Ubiquity of Cd makes it a serious environmental health problem that needs to be thoroughly assessed because it already affects or will affect large proportions of the world’s population. CLCE is a health problem that affects increasingly organ toxicity, especially nephrotoxicity, without a known threshold, implying that there is currently no safe limit for CLCE. In this chapter, we summarize current knowledge on the sources of Cd in the environment, describe the entry pathways for Cd into mammalian organisms, sum up the major organs targeted by acute or chronic Cd exposure and review the impact of Cd on organ function and human health. We also aim to put early pioneering studies on Cd poisoning into perspective in the context of recent ground-breaking prospective long-term population studies, which link CLCE to leading causes of diseases in modern societies – cancer, diabetes, and cardiovascular diseases, and of state-of-the-art studies detailing cellular and molecular mechanisms of acute and chronic Cd toxicity.


biomarkers cancer signaling toxicity transition metal transport 

Abbreviations and Definitions


multidrug resistance protein 1


multidrug resistance-associated protein 2


cystic fibrosis transmembrane conductance regulator


ATP-binding cassette sub-family G member 2; breast cancer resistance protein


apoptosis-inducing factor


protein kinase B


AMP-activated protein kinase


adenine nucleotide translocase


Atherosclerosis Risk Factors in Female Youngsters


activating transcription factor 6


adenosine 5'-triphosphate


Agency for Toxic Substance and Disease Registry


body weight


Bcl-2 homologous antagonist/killer


1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid


BAPTA acetoxymethyl ester


Bcl-2–associated X protein


blood-brain barrier


B-cell lymphoma 2


breast cancer resistance protein


Ca2+/calmodulin-dependent protein kinase II


cyclic 3'-5'-adenosine monophosphate




Clara-cell protein


cystic fibrosis transmembrane conductance regulator


cyclic 3'-5'-guanosine monophosphate


Chinese hamster ovary


CCAAT/-enhancer-binding protein homologous protein


chronic low cadmium exposure


canalicular multispecific organic anion transporter; multidrug resistance-associated protein 2




cAMP response element-binding


cyclosporin A


adrenocorticotropic hormone


copper-zinc superoxide dismutase




divalent cation transporter 1


dimercaptosuccinic acid


divalent metal transporter 1


DNA methyltransferase






helix-loop-helix structural domain in calcium-binding proteins


epidermal growth factor receptor


ethyleneglycoltetraacetic acid


eukaryotic translation initiation factor 2A


epithelial-to-mesenchymal transition




endoplasmic reticulum


ER-associated degradation


extracellular signal-regulated kinases


electron spin resonance


end-stage renal disease


European Union


Food and Agriculture Organization


pro-apoptotic type-II transmembrane protein; CD95L


ferroportin 1


post-mitotic Gap 1 cell cycle phase


post-mitotic Gap 2 / mitosis cell cycle phases


glutamate cysteine ligase catalytic subunit


glomerular filtration rate


growth hormone




guanosine 5'-triphosphate-binding protein


glutathione peroxidase


glucose-regulated protein, 78kDa


glucose-regulated protein, 94kDa




glycogen synthase kinase 3 beta






high molecular weight




International Agency for Research on Cancer


half maximal inhibitory concentration


intercellular adhesion molecule 1


International Cadmium Association


IκB kinase




inner mitochondrial membrane


inositol 1,4,5-trisphosphate


inositol-requiring enzyme 1


iron-regulated transporter 1; ferroportin 1


inhibitor of NF-κB


c-Jun N-terminal kinases


Kelch-like ECH-associated protein 1


kidney injury molecule-1


Michaelis constant


microtubule-associated protein 1 light chain 3


median (50%) lethal dose


lactate dehydrogenase


lymphoid enhancer factor-1 transcription factor


low molecular weight


low-density-lipoprotein-related protein


mitogen activated protein kinase


mitochondrial calcium uniporter




Madin-Darby canine kidney (cells)


murine double minute 2


multidrug resistance protein 1


mitochondrial membrane potential


manganese superoxide dismutase


minimal risk level


multidrug resistance-associated protein 2




mammalian target of rapamycin


metal-transporter protein 1; ferroportin 1


molecular weight


nicotinamide adenine dinucleotide phosphate (reduced)




nuclear factor-κB


neutrophil gelatinase-associated lipocalin


Third National Health and Nutrition Examination Survey


nitric oxide


nitric oxide synthase


natural resistance-associated macrophage protein-2


NF-E2-related factor 2

O\( _2^{\bullet - } \)

superoxide anion


outer mitochondrial membrane


peroxinitrite anion


Occupational Safety & Health Administration from the US Dept. of Labor


p38 mitogen activated protein kinase


tumor suppressor protein 53


poly (ADP-ribose) polymerase




protein kinase RNA-like endoplasmic reticulum kinase


placental growth factor


phosphoinositide 3 kinase


phosphatidylinositol 4,5-bisphosphate


phosphatidylinositol (3,4,5)-triphosphate


protein kinase A


protein kinase C


proximal tubule


permeability transition pore




rat sarcoma proto-oncogene


receptor-mediated endocytosis


reactive oxygen species


sarco/endoplasmic reticulum Ca2+-ATPase




sonic Hedgehog


superoxide dismutase


specificity protein 1 transcription factor


signal transducer and activator of transcription 3 transcription factor


T-cell specific transcription factor 1


tumor necrosis factor α


transient receptor potential (channel)


transient receptor potential malastatin 7 (channel)


transient receptor potential vanilloid 5,6 (channel)


thyroid-stimulating hormone


urinary NGAL


unfolded protein response


voltage-dependent anion channel


vascular endothelial


World Health Organization


wingless/Int-1 signaling protein


X-box binding protein 1


Zrt-/Irt-like protein


mitochondrial membrane potential



The authors acknowledge the scientific contributions of past and present coworkers, in particular Drs. M. Abouhamed, P. K. Chakraborty, J. M. Friedmann, C. Langelüddecke, and N. A. Wolff. Research in the laboratory is funded by The German Research Foundation (DFG) (grants FT345/8-1 to FT345/11-1) and the Centre for Biomedical Research and Training (ZBAF) at the University of Witten/Herdecke.


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© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Centre for Biomedical Training and Research (ZBAF), Institute of Physiology & Pathophysiology, Faculty of HealthPrivate University of Witten/HerdeckeWittenGermany

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