cadmium toxicity

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#Crimean Federal University# Cadmium Toxicity in Kidney Presented by :Pavan Barot Group:218 Subject:Ecological Physiol

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#Crimean Federal University#

Cadmium Toxicity inKidney

Presented by :Pavan Barot Group:218 Subject:Ecological Physiology

INTRODUCTIONEncountered 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

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

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

Toxicity Primary effects on kidneys Emphysema, Kidney, Calcium metabolism, Possible kidney

carcinogen. Secondary effects on urinary 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

Effectskidney toxicity:

Edema and Emphysema by killing macrophages

Skeletal effects: Osteoporosis and osteomalacia (pseudofractures)

Cancer: Carcinogenic in animal studies Approx.8% of lung cancers may be attributable to Cd

Inhibition of DNA repair

Cell damage

Oxidative stress

Enhancement of DNA damage

Decrease of Antioxidants

Activation of cellular signals

Inhibition of DNA Methylation

E-cadherin dysfunction

DNA damage

Induction of Proto-Oncogenes

Disruption Cell Adhesion

Induction of Apoptosis

Gene Mutation

Promotion of proliferation

Malignant Cancer

Preneoplastic lesion

Cd+2

A Model: Major mechanism involved in Cd+2 Carcinogenesis

Cadmium epidemics

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)

Metabolism, storage and excretion of cadmium in human body

Journal of Occupational Medicine and Toxicology 2006

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

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

Mechanism responsible for the selective accumulation of cadmium in proximal tubular cells

Mechanism

Proposed pathways for ROS in Cd toxicology and carcinogenesis following acute and chronic exposures

EFFECTS OF POISONING:

SYMPTOMS Food poisoning (ingestion) Bronchitis (inhalation) Interstitial pneumonitis (inhalation) Pulmonary edema (inhalation) MEDICAL CONDITIONS Osteoporosis Osteomalacia Hyperuricemia Hypophosphatemia Itai-itai disease Renal failure

DIAGNOSISDIRECT EVALUATION 24 hour urine cadmium – reflects exposure over time Blood

cadmium-estimated INDIRECT EVALUATION Urinary ß 2 -microglobulin – evaluate urine levels > 300 g/g

creatinine Urinary retinol-binding protein(RBP)Urinary Metallothionein (MT)

Critical levels: blood cadmium: 10 micrograms/l Urinary cadmium: 10 micrograms/g creatinine Urinary beta 2-microglobulin: 2000 micrograms/g creatinine Urinary retinol-binding protein: 200 micrograms/g creatinine

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.

TREATMENT

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

Reference

• Wikipedia (heavy metal toxicity)• Google(toxicity of cadmium)• @Web search :effects of cadmium on kidney

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