Mycotoxins

Question 1

Aflatoxin

Metabolism and mechanism of action:

Answer 1

• In an organism, they are metabolised by cytochrome P450 into unstable epoxide
derivates. Part of them bind covalently to DNA (forming adducts) and lead to genotoxic and carcinogenic effects. Then changed by hydroxylation to less toxic aflatoxins M1, M2, GM1, GM2, which are excreted not only in urine and faeces, but can be found also in milk, meat and eggs
• All aflatoxins are hepatotoxic and immunosuppresive, and sometimes also damage GIT or kidneys

Question 2

Ochratoxin

Mechanism of action:

Answer 2

• Ochratoxins block proteosyntesis due to exchange with phenylalanine during
formation of respective tRNA and during protein chain formation. Also probably
increase oxidative stress
• Ochratoxins are primarily nephrotoxic, but can affect also GIT and liver
• During chronic exposition act as immunosuppressive, teratogenic and potentially
carcinogenic agents
• They undergo enterohepatic cycle and persist in the body for approximately 1 month

Question 3

Patulin

Mechanism of action:

Answer 3


• Patulin binds to –SH groups of proteins and changes functions of enzymes and proteins, increases permeability of cell membranes
• Acute poisoning is seen in farm animals fed with waste from cider houses etc. and include GIT and neurological signs.
• In humans and some herbivorous pet animals chronic poisoning is more possible and involves teratogenic and immunosuppresive effects

Question 4

Tremorgenic mycotoxins

Answer 4

Mechanism of action:
 Inhibition of inhibitory neurotransmitters GABA and glycine, or stimulation of
receptors for excitatory neurotransmitter glutamate. All mechanisms lead to
hyperexcitation
 Clinical signs may involve GIT signs like vomiting and diarrhoea, but are typical with
long lasting (hours to days) and hard to treat tremors and convulsions

Question 5

Trichotecens

Mechanism of action:

Answer 5

• They all inhibit proteosynthesis, usually by inhibiting the enzyme peptidyltransferase,
  which is important for the elongation of protein chain. Some also induce apoptosis, damage DNA and RNA and mitochondrial function (celullar breathing and energy production).
• They affect mainly quickly growing and reproducing cells
• The effects are: Gastrotoxicity - vomiting, diarrhoea, inappetence, malnutrition;
  haematotoxicity – damage of haematopoetic and lymphatic tissues; immunosuppression, dermatotoxicity – damage of hair folicules and skin cells

Question 6

Zearalenone

Answer 6

Mechanism of action:
- Significant estrogenic effect
- Causes vulvovaginitis, swelling of nipples, disturbs sexual hormones cycle, problems
with conception, abortions etc.

Question 7

Fumonisines

Answer 7

Mechanism of action:
- Interference with sphingolipid metabolism. Lacking sphingolipids are problem for
membrane function of all cells
- In all species liver damage, where sphingolipids are synthesized, appears
- Horses are sensitive to lack of sphingolipids in myelin sheaths in neurons and suffer
from a disease called ELEM (Equine leucoencephalomalacia) which results in
paralysis of muscles and failure of vital centres in brain
- Pigs suffer from lack of sphingolipids in myocardial cells and develop cardiac failure
with lung oedema (PPE – porcine pulmonary oedema) and die from suffocation
- Fumonisines are also promoters of carcinogenesis and tumours of oesophagus and
liver were observed after chronic intake of minimal doses