4.6 Metals and Environmental Toxicants Flashcards
Forms of Metals and their basic toxicological properties
- Metallic (elemental forms)
>As a general rule have low solubility and toxicity - Inorganic salts (chloride, acetate, sulfate, etc)
> More water soluble, reactive, bioavailable
> Some forms more toxic
» e.g. As3+ >As5+; Fe2+ >Fe3+ - Organic (carbon-bound)
> Lipid soluble, readily absorbed, neurotoxic
dose response to metals
problems if too little or too much > want to be in “sweet spot”
-response shifts due to variety of factors
Toxicology of Metals: Mechanisms (4)
- Association with polar groups
* Thiol residues, histidine, porphyrins, etc - Ionic interactions with charged residues
* Carboxylic acids
* Substitution for other ions, e.g. Ca++ - Generation of free radicals
* Fe++, Cu++, etc - Haptens and immunostimulants
* e.g. Ni binds to keratohyalin, filaggrin, etc.
* Aluminum and mercury used as adjuvants
most metals are toxic-actors in this way
direct-acting toxicants
mechanism of action of nephrotoxic metals
Nephrotoxic metals (Hg, Cd, Pb, U, etc)
1. Bind to metallothionein (MT)
2. Small protein not retained by glomerulus
3. Reabsorbed in proximal tubule (PT)
4. Accumulates to nephrotoxic levels
5. Mitochondrial damage - Tubular necrosis
can metals cause problems by binding proteins?
yeah
lead major target organs; acute and chronic
Acute: GI tract, brain, kidney
Chronic: Bone marrow, peripheral nerves
copper major target organs; acute and chronic
Acute: GI tract, liver
Chronic: Erythrocytes, liver, kidney
iron major target organs; acute and chronic
Acute: GI tract, liver
Chronic: Erythrocytes, liver, kidney
zinc major target organs; acute and chronic
Acute: GI tract
Chronic: GI tract, hemolysis
selenium major target organs; acute and chronic
Acute: CNS, muscle
Chronic: Integument (hoof and hair)
aresenic major target organs; inorganic, organic
Inorganic: GI, kidney; Organic: Neuropathy
mercury major target organs; inorganic, organic
Inorganic: GI, kidney; Organic: Neuropathy
absorption of copper in sheep - mechanism of toxicity
- Sheep are efficient at taking up Cu from the diet
- Tend to accumulate Cu (slow excretion)
- Accumulate more if molybdenum is low
- Store copper in macrophages and hepatocytes (cause some hepatopathy over time)
- Experience some acute period of hepatic necrosis or stress
> Release copper into blood > Free radical generation causes massive hemolysis and hepatic necrosis
treatment and prevention of copper toxicity in sheep
- Sodium molybdate and sodium thiosulfate
- Avoid Cu supplemented feeds intended for other species
where do sheep store excess copper? what problems can arise?
Excess copper stored in hepatic macrophages
– seepage/release leads to chronic injury to liver
what effect does copper released from liver in sheep have?
hemolytic > hemoglobin casts in kidneys, intravscular hemolysis, icterus, methemoglobin, hemoglobinuria
Copper and chronic liver disease - Dogs. what breed? how does it arise?
Inherited in Bedlington terriers (Cu homeostasis)
Deletion of COMMD1 (MURR1) gene
Non-familial and idiopathic in other
breeds
> Doberman, Westie, Dalmatian, Labrador, etc.
Very high levels of lysosomal Cu in hepatocytes - 500-2000 ppm
Lysosomes stain with rhodamine in histologic sections
what does chronic liver disease look like in PM and clinical signs in a dog?
Chronic necroinflammatory liver injury
> High liver [Cu] in 34% of dogs with chronic
hepatitis
> Cirrhosis in severe cases
Gastrointestinal signs, elevated liver values
Hemolytic crisis is unlikely
Reduce copper with chelation therapy
> D-penicillamine (long course)
> Triethylene tetramine dihydrochloride (trientine)
what problems can excess iron cause? what is an important nutrient to stop this?
-Iron causes free radical formation and lipid peroxidation, OH adducts and DNA breaks
-Vitamin E and Selenium have important antioxidant properties
when is iron toxicity most common in piglets? what do we see in PM?
– most common when piglets or sow are vitamin E or selenium deficient!
-acute liver necrosis, myocardial necrosis
effects of zinc toxicosis?
GI upset; renal failure Hemolysis; hemoglobinuria
spider bite signs
*Cats are the species that most often get
black widow spider bites
* Painful bites, muscle cramps, paralysis
blister beetle toxin and signs
- Blister beetles contain cantharidin
*Necrosis and vesicles – oral, alimentary tract
what can some caterpillars cause in mares?
- Placentitis and abortions in mares
what do rattlesnake bites contain and cause?
Phospholipases, Coagulation factors, Myotoxic peptides, Other toxins
-Painful wounds with local swelling
-Local necrosis and hemorrhages
-Coagulation problems
-Rhabdomyolysis (muscle necrosis) and myoglobinuria
-Hemolysis and hemoglobinuria sometimes
-Shock and circulatory collapse
Environmental Polychlorinated Compounds - whre do we fins them, what problems do they cause?
*Industrial applications (fire retardants, dielectrics, etc)
*Persist in the environment
*Bioaccumulate in animal tissues
*Endocrine disruptors
*Produce tumours in rats and mice
what lesions do we see connected with oil spills?
various driller chemicals can cause oxidant RBC injuries
