11. Toxicants: Circulatory & Hematopoietic Systems

mycotoxins produced by the fungus fusarium verticillioides

fumonisins

Fumonisin Induced Porcine Pulmonary Edema:

• ingestion → inhibits ________ ____ ________ → increase ________

• inhibition of ____ ________ ____ ________ → ________ myocardial contractility

• ________ side heart failure → ________ ________

• sphingosine N acetyletransferase; sphingosine

• L type Ca channel; decrease

• left; pulmonary edema

Fumonisins cause what organ damage in multiple species, including pigs, horses, cattle, rabbits, and primates?

liver

What specific organ is targeted by fumonisins in pigs?

lung

What specific organ is targeted by fumonisins in horses?

brain

What specific organ is targeted by fumonisins in rats, rabbits, and sheep?

kidney

What specific organ is targeted by fumonisins in rats and pigs?

esophagus

What is the agent in ergot toxicity?

claviceps purpurea

In ergot toxicity, what are the grains replaced by?

ergot sclerotia that contain the toxins

What are major factors in the content of ergot containing grain?

growing conditions and storage

Grains infected with claviceps purpurea can produce what toxic agents?

ergonovine, ergotamine, ergopeptines

Grain yields can be ________ by the content of ergot.

downgraded

True or false: Absorption of ergot has not been well studied but absorption occurs readily in both ruminants and non-ruminants.

true

When injected as a drug, what is the removal of ergot?

primarily by hepatic metabolism

How is most ergot toxicity effects produced?

by acting agonistically at biogenic amine receptors in the animal’s body

What are the mechanisms of toxicity in ergot toxicity?

A
S
D

• alpha adrenergic

• serotonergic

• dopaminergic

How is ergot toxicity diagnosed?

detection of ergot in grain

What are symptoms associated with ergot toxicity?

C
H
A
P
G
G
D

• convulsions

• hallucinations

• abortion

• paralysis

• GI disturbance

• gangrene of extremities and death

• dystocia and other complications with pregnant animals

In fescue toxicity, what is the infecting endophyte?

neotyphodium coenophialum

What is by far the most prevalent ergopeptine that accounts for approximately 90% of the ergopeptine alkaloid content of tall fescue? What else is also present?

ergovaline; lysergic acid amides (ergoline alkaloids), clavine alkaloids, and the peptide or peptine alkaloids

What are some symptoms of fescue toxicity?

P
D
H
N
N
N

• panting

• drooling

• heavy respiration

• not eating

• not moving

• not shedding

• long periods in water

What is the toxic component of black walnut?

juglone

How is juglone absorbed?

through the coronary band and skin

In black walnut toxicity, what may be a result of an off-target inhibition? What does it lead to?

blood and bone marrow toxicity; decreased bone marrow response or a result of peripheral effects leading to destruction of blood cells

What is another major mechanism of toxicity when it comes to black walnut toxicity?

formation of reactive oxygen species (ROS), including superoxide anion, hydrogen peroxide, and hydroxyl radical

What does warfarin affect?

vitamin K reductase

The molding of sweet clover promotes the likelihood of what toxin in the hay?

dicumarol

Concentrations of what amount of dicumarol are usually required to cause poisoning in cattle?

20-30 mg/kg of hay ingested throughout several weeks

All anticoagulants have the basic ________ or ________ nucleus.

coumarin; indanedione

What is an example of a first generation anticoagulant? What is needed as far as feedings go for it to be toxic?

warfarin; require multiple feedings

What is an example of an intermediate anticoagulant? What can be said about the feedings required for toxicity?

diphacinone; require fewer feedings than first generation and are more toxic to nontarget species

What is an example of a second generation anticoagulant? What feedings are required for toxicity?

brodifacoum; highly toxic to nontarget species after a single feeding

What do the allium species contain?

wide variety of organosulfoxides, particularly alk(en)ylcysteine sulfoxides

What is the toxic principle of the allium species? How are they formed?

sulfur-containing organic compounds; trauma to the plants, such as chewing, converts them to this

What amount of onions in cats has resulted in clinically important hematologic changes? What about dogs?

5 g/kg; 15-30 g/kg

Onion toxicosis is consistently noted in animals that ingest what?

more than 0.5% of their body weight in onions at one time

What is the toxicologic mechanism of the allium spp?

oxidative hemolysis

What does allium toxicity cause to form in the blood? Why?

heinz bodies; sulfhemoglobin is less soluble than hemoglobin, so it precipitates, aggregates, and binds to the cell membrane

Cat presents with puffy face, puffy paws, and pale MM with low PCV and methemoglobininemia. What is at the top of your DDX?

acetaminophen toxicity

What is the toxic compound in acetominophen toxciity?

para-aminophenol

What is the treatment for acetaminophen toxicity?

N-acetylcysteine