TRICHOTHECENES

DR.TRISHA
M-6177
M.VSc.Scholar, Division of medicine
INTRODUCTION

 Trichothecenes - very large family of chemically related

toxins produced by various species of Fusarium,
Myrothecium, Trichothecium, Trichoderma,
Cephalosporium, Stachybotyrs
 Over 140 known metabolites but most commonly found-
T-2 toxin, deoxynivalenol ( vomitoxin, DON) &
diacetoxyscirpenol (DAS)
 Toxic effects of T-2 was first documented in 1940s when
it was associated with an outbreak of alimentary toxic
aleukia in human beings
 Affect all species including human beings and are
amongst the most toxic mycotoxins
TOXICITY

 Toxic to mammals, birds, fish , many invertebrates, plants and

eukaryotic cells
 Mice are more resistant than rats, guinea pigs, swines and
chickens
 Cats appear to be more sensitive to T-2 toxin than other
domestic species
 The acute oral LD50 of T-2 toxin in various species is : rats 3.8
mg/kg, day old broiler chicks 5-5.25mg/kg and swine 4.0
mg/kg. For DAS, the acute oral LD50 is 1-2 mg/kg for guinea
pigs, 7.3 mg/kg for rats and 3.8mg/kg for day old broiler chicks.
For DON, the acute oral LD50 is 46 mg/kg in mice
Cont….

 Dietary levels of T-2 toxin capable of causing poor growth,

decrease production or pathological effects are; cattle 2 ppm
for several months , swine 1-8 ppm for 8 weeks, chicks 0.4
ppm for 7-9 weeks or 1 ppm for 3 weeks and laying hens > 16
ppm for 28 days
 Species –swine, cattle refuses to eat feeds containing large
amount of T-2 toxin , so it is called as refusal factors in mould
grains
TOXICOKINETICS

 Trichothecenes mycotoxins are lipophilic agents, so they are

easily absorbed through skin, gut and pulmonary mucosa.
 Once, trichothecene mycotoxins enter the systemic circulation,
regardless of the route of exposure they affect rapidly
proliferating tissues
 In liver, microsomal enzymes rapidly metabolise trichothecene,
some of the metabolites are toxic
 Excretion of trichothecenes and their metabolites is mainly by
faeces and urine; to some extent they may be present in
poultry eggs and cattle milk
MECHANISM OF ACTION

 Highly toxic at subcellular, cellular and organic system levels

 Swiftly penetrates cell lipid bilayer and gain access to DNA, RNA
and cellular organelles
 Inhibition of protein synthesis appears to be the principal MOA , but
recent studies have indicated the diverse effects:
1. Potent inhibitors of protein synthesis in mammalian cells. The T-2
toxin interacts with 60S subunit of ribosomes - inhibits protein
synthesis possibly by degrading polyribosomes and blocking
initiation, elongation and termination of protein synthesis. Lack of
essential proteins and enzymes impairs various cellular activities
such as mitochondrial electron transport mechanism- cell death
Cont…

2. In doses higher than those required to inhibit protein synthesis,

trichothecenes inhibit DNA &RNA nucleic acid synthesis
3. Low dosages of trichothecenes inhibits membrane transfer of glucose,
calcium and some amino acids. These effects are independent of
the inhibition of protein synthesis.
4. Directly cytotoxic to a variety of cells. Referred to as radiomimetic effect
5. Induce some alterations in membrane structure, which consequently
stimulates lipid peroxidation. Toxin stimulated alterations in
mitochondrial membrane contributes to the effects on cellular
energetics and cellular cytotoxicity
6. Affect immunity, main immunosuppressive effect is at the level of T
suppressor cells
Cont…

7. Toxins cause haemorrhages by producing depression of clotting factors,

thrombocytopenia and inhibition of platelet function or possibly
combination of these
8. Irritant to skin and mucous membranes and produce gastroenteritis.
 CLINICAL SIGNS

 Can be acute or chronic

1. ACUTE TOXICITY: vomition , colic, poor appetite, lethargy,
weakness , mucous or bloody diarrhea , dehydration ,
hypothermia, untriftiness, abortion, hematuria, epistaxis,
hypotension & shock
 Paresis , tremors, seizures and paralysis occurs in almost all
species
 Death could occur within minutes, hours or days and is mainly
attributed to hypotension & shock
 In horses: retarded reflexes, bradycardia, disturbed respiration,
cyclic movement, convulsions & death
Cont….

2. CHRONIC TOXICITY: Responsible for ATA

( alimentary toxic aleukia)
 ATA toxicosis – weakness, salivation, abdominal pain, leucopenia,
granulopenia and progressive lymphocytosis , bright red or dark
cherry red petechial rashes on the skin
 Most severe cases: intensive ulceration and gangrenous
processes develop in the larynx leading to aphonia & death by
strangulation
 In animals: seen in form of infertility or poor litters, poor weight
gain, poor hatchability, decrease egg production & egg shell
thickness
POST-MORTEM FINDINGS

 Oral, oesophageal, abomasal & ruminal erosions along with

haemorrhagic enteritis and erosions
 Mucosal membranes & visceral organs may have petechial or
ecchymotic haemorrhages
 Liver may show necrosis
Cont….

 Lymphatic organs are smaller than normal

 In chicken , focal yellow-white caseous plaques at beak
margins, on hard palate, or along edge of tongue
 Spleen may decrease in size
DIAGNOSIS

 Difficult- clinical signs are non specific or masked by

secondary infections,, rapidly metabolised and excreted
 Analysis of toxins in feed or grains by-
1. TLC
2. HPLC
3. ELISA
CONT…

 Extracts of mouldy corn produce a characteristic reaction when

applied to skin of laboratory animal if T-2 toxin is present.
TREATMENT AND MANAGEMENT

 No specific treatment
 Treated symptomatically for GI signs, skin & oral lesions,
toxemia & shock
 Stress & exposure to animals with potential infectious diseases
should be avoided to prevent potentially immunosuppressed
animals from becoming infected
REFERENCES

 Sandhu H.S. amd Brar R.S. 2009. Textbook of veterinary

toxicology