2. INTRODUCTION
Encountered in earth’s crust combined with chlorine (CdCl2),
oxygen (CdO),sulphur (CdS)
Exists as small particles in air, result of smelting, soldering
or other high temp. industrial processes
By-product of smelting of zinc, lead, copper ores
Used mainly in metal plating, producing pigments,
batteries, plastics and as a neutron absorbent in nuclear
reactors
3. CADMIUM POISONING
Caused by excessive exposure to cadmium
No constructive purpose in the human body.
Extremely toxic even in low concentrations, and
will bioaccumulation in organisms and ecosystems
The McDonalds Shrek Glasses are contaminated
with Cadmium
4. EXPOSURE SOURCES
Tobacco smoke (a one pack a day smoker
absorbs roughly 5 to 10 times the amount
absorbed from the average daily diet)
Tobacco smoke is an important source of
cadmium exposure
Cadmium a component of chuifong tokwan ,
sold illegally as a miracle herb in china.
Low levels are found in grains, cereals, leafy
vegetables, and other basic foodstuffs
5. Toxicity
Primary effects on lungs & kidneys
Lung, Emphysema, Kidney, Calcium metabolism, Possible lung
carcinogen.
Secondary effects on skeletal system
Mechanisms
Binds to sulfhydryl groups, displacing other metals from
metalloenzymes, disrupting those enzymes
competing with calcium for binding sites (calmodulin)
Kidney toxicity
Free Cd binds to kidney glomerulus
Proximal tubule dysfunction
6. Contd…
Lung toxicity:
Edema and Emphysema by killing lung macrophages
Skeletal effects:
Osteoporosis and osteomalacia (pseudofractures)
Cancer:
Carcinogenic in animal studies
Approx.8% of lung cancers may be attributable to Cd
7. A Model: Major mechanism involved in Cd+2 Carcinogenesis
Enhancement of DNA
Inhibition of DNA repair damage
DNA Gene
damage Mutation
Preneoplastic
Decrease of Antioxidants Oxidative stress
lesion
Cd+2 Activation of cellular Induction of Proto- Promotion of
signals Oncogenes proliferation
Inhibition of DNA
Methylation
Malignant
E-cadherin dysfunction Disruption Cell Adhesion Cancer
Cell damage Induction of Apoptosis
8. Cadmium epidemics/case studies
Japan (1950s) “Itai-Itai” is Japanese for “ouch-ouch”-refers to
bone pain related to calcium loss
Renal failure,Anemia, severe muscle pain
River polluted with waste from factory, water used on rice fields
for many years
Rice accumulated high level of Cd Community was poor (and
therefore malnourished with respect to calcium)
9. Metabolism, storage and excretion of cadmium in
human body
Journal of Occupational Medicine and Toxicology 2006
10. Mechanism
Two mechanisms are involved in cadmium mutagenicity,
Induction of reactive oxygen species and
Inhibition of DNA repair
Cystein is a precursor to the anti-oxidant protein glutathione and
is also required for metallothionein which is a protein that binds
to cadmium specifically
Intracellular, cadmium binds to metallothionein
Cadmium is released into the plasma after haemolysis or when
the erythrocytes lifetime has expired
Cadmium is transported in blood plasma initially bound to
albumin
Cadmium bound to albumin is preferentially taken up by the liver
11. Contd..
In the liver, cadmium induces the synthesis of
metallothionein
After a few days exposure metallothionein-bound
cadmium appears in the blood plasma
Plasma metallothionein play an important role in
transport of cadmium
Bound to sulfhydryl groups of cystein residues
After chronic exposure, cadmium accumulates in the
liver then redistributed slowly to the kidney
13. Cadmium-induced apoptosis involves two main
pathways
• Extrinsic pathway Fas- FADD caspase-8 pathway initiated by ligand-induced activation
of the death receptors (such as Fas) at the plasma membrane resulting in the
activation of caspase-8 or caspase-10
• Intrinsic pathway triggered by cellular stress signals (such as DNA damage) activating
caspase-9. Caspase-8 and caspase-9 cleave and activate the effector caspases
caspase-3 and caspase-7, which kill the cells by cleaving a wide range of protein
substrates
• cadmium induced cell death seems to be associated with caspase-8 activation (via
FAS receptor) followed by BID cleavage and induction of mitochondria caspase
cascade after release of cytochrome C .
• Apoptosis may also be induced by caspase-independent events after intoxication,
maybe by Ca2+-calpain coupled processes or by translocation to the nucleus of
apoptosis-inducing factor (AIF)
15. Cadmium induces ROS production
Cadmium exposure causes oxidative stress, which is not due to
direct involvement of cadmium in the production of ROS but
through indirect processes like decrease of cellular anti-oxidants
and exhalation of ROS from mitochondria
Surprisingly, the activities of superoxide dismutase (SOD) and
glutathione peroxidase (GPx) are reduced after 4 h but increased
again after 8 h of intoxication
The reduction of glutathione levels after cadmium administration is
also shown to occur in mice.
The reduction of the activities of antioxidants may lead to the
production of ROS species like H202, OH and O2–. This
overproduction of ROS is partly responsible for the DNA damage.
16. Proposed pathways for ROS in Cd toxicology and carcinogenesis
following acute and chronic exposures
20. TREATMENT
Elements like calcium and selenium are shown to
have protective effect against cadmium-induced
toxicity
Adequate levels of zinc in the body helps to
displace cadmium from the tissues
Potent antioxidants like Vitamin C, E,glutathione,
methionine, glycine, cysteine has great protective
efficiency.
21. TREATMENT:
Smoking should be avoided and do check
your house products for compounds which
contain cadmium
Render gastric lavage or make the infected
person vomit within an hour if the person has
consumed cadmium salts
Chelation therapy