Toxicants Affecting the Liver & GI Tract I (12)

Question 1

What lobule of the liver is more susceptible to injury?

Answer 1

centrilobular zone (the least oxygenated also)

Question 2

What are factors for hepatic toxicity?

Answer 2

first pass effect - close contact with circulation

iron and copper homeostasis

Question 3

Review types of liver injury

Answer 3

Question 4

What do pyrrolizidine alkaloids cause?

Answer 4

irreversible hepatic damage

toxicity signs are a consequence of impaired liver function

crotalaria intoxication: leads to pulmonary damage as a primary effect

Question 5

What are the toxicants in showy rattle box aka crotalaria?

Answer 5

monocrotaline
spectabiline

pulmonary damage as primary effects

Question 6

What is the toxicant in tansy ragwort (senecio)?

Answer 6

pyrrolizidine alkaloids

Question 7

What is the mechanism of toxicity of pyrrolizidine alkaloids like in tansy ragwort?

Answer 7

pyrrolizidine alkaloids are potent electrophiles (ROS species) so they react with nucleophilic substrates including DNA, amino acids, and proteins

attack soluble nucleophiles such as glutathione

Question 8

What are clinical signs of pyrrolizidine alkaloid toxicity?

Answer 8

Acute liver failure, anorexia, depression, icterus, edema

Chronic: photosensitivity, icterus, and increased susceptibility to other liver insults

Question 9

How do you diagnose pyrrolizidine alkaloids?

Answer 9

unusually high elevations of liver enzymes: increased bilirubin and
bile salts are seen in acutely intoxicated animals

Hepatic necrosis with fibrosis and biliary proliferation are seen histologically

Question 10

What is the most dangerous mushroom?

Answer 10

the “death cap” or “death angel”

Question 11

What are the toxicants in amanita mushroom?

Answer 11

amatoxins and phallotoxins

Question 12

What is the MOA for amanita toxins?

Answer 12

inhibits nuclear RNA polymerase = decreased protein synthesis and cell death

Question 13

What are the 4 phases of intoxication with amanita?

Answer 13

1) asymptomatic latency (0-6 hours)

2) GI symptoms including nausea, diarrhea

3) lag period, seems to recover

4) about 2 days later, liver and kidney organ failure

Question 14

What are the toxicants in sago palms (cycads)?

Answer 14

cycasin
beta-methylamino L-alanine (BMAA)

Question 15

What does cycasin cause?

Answer 15

hepatic necrosis and GI irritation

Question 16

What does Beta-methyl-amino L-alanine (BMAA) cause?

Answer 16

neurotoxic amino acid, causing muscle weakness, paralysis, and seizures

Question 17

What is the MOA of the toxicants in cycads?

Answer 17

not well understood - is mutagenic, carcinogenic, and teratogenic as well as hepatotoxic

Question 18

What is the toxicant in cocklebur?

Answer 18

Carboxyactractyl-oside (CAT)

Question 19

What is the MOA for cocklebur? Effects?

Answer 19

Inhibits ADP translocase on the cytosolic side of the mitochondrial membrane

Severe, diffuse, centrilobular hepatocellular necrosis

Question 20

What are aflatoxins?

Answer 20

mycotoxins of aspergillus and penicillium

Question 21

What has aflatoxins?

Answer 21

aspergillus
penicillium

Question 22

Which species is especially susceptible to aflatoxicosis?

Answer 22

turkeys

Question 23

What is the effect of aflatoxins?

Answer 23

Liver disease, carcinogenic, teratogenic effects

Microscopically, the liver is enlarged and shows marked fatty accumulations and massive centrilobular necrosis

Question 24

What are the effects of alsike and red clovers - hepatoxins?

Answer 24

lead to chronic liver failure primarily in horse - mechanism unknown

Question 25

What is the MOA for copper toxicosis in sheep?

Answer 25

Copper accumulates in liver → hepatocellular damage → stressful event → Cu released into blood, damage to red blood cells → Cu and Hb goes to kidneys and causes renal damage

sheep