MYCOTOXINS

Dr. Afroz Jahan

(Veterinary Pharmacology & Toxicology)
College of Veterinary Science, Rampura Phul
• MYCOTOXINS are secondary fungal metabolites that cause illness /death
in other species.
• Immunosuppressive- resulting in secondary diseases.
• Classification according to the main organ system they affect.
I. Hepatotoxic: Aflatoxins, Rubratoxins, Sporidesmin
II. Nephrotoxic: Ochratoxin, Citrinin
III. Oestrogenic: Zearalenone (F-2 toxin)
IV. Cytotoxic: Trichothecenes (T-2 toxin)
V. Neurotoxic: Tremorgens
VI. Miscellaneous: Ergot, Fescue, Patulin
 AFLATOXINS

• Produced by Aspergillus flavus, A. parasiticus.

• Four important aflatoxins B1, B2 & G1, G2
• Aflatoxin B1 most abundant & toxic.
• Dogs, rats, rabbits are highly susceptible
• Adult cattle, S/G relatively resistant.
• Young> adult, Male> female
• Aflatoxins are carcinogenic, mutagenic, teratogenic and
immunosuppressive.
• Metabolism in liver, converted to metabolites.
• AflatoxinB1 8,9 epoxide is highly reactive metabolite.

• M1 is metabolite of B1 . Found in urine, milk & tissues.

• MECHANISM OF ACTION:
• Binds covalently to DNA, RNA & proteins – inhibits protein synthesis.
• Epoxide binds to N-7 guanine residue; mispairing- incorrect codon.
• Impaired protein synthesis.
• Hepatic steatosis, excess accumulation of lipids.
• Decrease in prothrombin & Vitamin K- haemorrhages.
• CLINICAL SIGNS:
I. Acute toxicity: epistaxis, petechiae on mucus membrane, icterus,
convulsions , death
II. Subacute: Hypoprothrombinemia, haemorrhagic enteritis,
photosensitive dermatitis.
III. Chronic: Most common. Decrease in feed efficiency, rough hair coat.
Abortions.
• In poultry, interfere with absorption of lipids- decrease egg production &
size.
• PM findings: in acute cases- enlarged liver, massive centrilobular
necrosis & haemorrhages.
• Chronic cases: diffuse liver fibrosis, hydrothorax
• Diagnosis: Aflatoxin M1 can be detected in milk/urine , elevated
serum liver enzymes
• Treatment: No specific treatment.
• Hydrated sodium calcium aluminosilicate as feed additive adsorb
toxin.
• Vit.E & Se supplementation
• Treatment of grains with anhydrous ammonia to reduce aflatoxin
content.
 RUBRATOXINS

• Produced by Penicillium rubrum.

• First recognised as Haemorrhagic syndrome in poultry.
• Rubratoxins- A & B
• Rubratoxin B is most toxic. Hepatotoxic, mutagenic & teratogenic.
• Similar to aflatoxins, bind to macromolecules.
• Blocks ETC & ATPases- lethality.
• Severe liver damage- anorexia, dehydration, jaundice .
• Presence of toxin in feed & urine.
• Symptomatic treatment.
 SPORIDESMINS

• Produced by Sporidemium species.

• Extensive damage to liver- Acute biliary obstruction.
• Chlorophyll not completely metabolised- photosensitization &
blistering of skin.
• Facial eczema
• Clinical signs: anorexia, jaundice & photosensitive dermatitis.
• Exposed areas of skin- reddened- crusty & dark- susceptible to
infections.
• Hyperirritability, haemolysis, haemoglobinuria.
• PM findings: swollen mottled liver, thickened bile duct walls,
necrotic lesions on face & other light pigmented areas.
• Treatment : animal should be immediately shifted to shaded area.
• Supportive treatment for hepatitis & photosensitization
• Antibiotics & antihistamines
• Zinc sulphate in drinking water- hasten recovery of affected wounds.
 OCHRATOXINS

• Produced by Aspergillus ochraceus, Penicillium viridicatum

• Potent nephrotoxin , syndrome called mould nephrosis/ mycotoxic
nephropathy
• Ochratoxin A- common and most potent
• Swine & poultry most susceptible.
• Acts on renal proximal tubule.
• Inhibits release of brush border enzymes
• Increase generation of free radicals.
• Clinical signs: in acute toxicity---- vomition, diarrhoea, dehydration.
• Chronic toxicity-----polyuria, polydipsia, dehydration.
• Immunosuppression, teratogenicity, carcinogenicity, haemorrhages.
• Decrease sperm quality in boars & abortion in sows.
• PM findings: renal tubular swelling, atrophy of tubular epithelium.
• Diagnosis : analysis of grains using TLC/HPLC
• Increase in BUN , Serum creatinine
• Treatment :
• Activated charcoal
• Don’t use animal feed if level is > 10ppb
• Supportive therapy.
 CITRININ

• Produced by Penicillium & Aspergillus

• Co-contaminant with ochratoxins.
• Produces mycotic nephropathy in livestock.
• Pigs are highly sensitive
• Cause kidney damage
• In birds, decrease in FCR due to kidney degeneration.
 OESTROGENIC MYCOTOXINS

• ZEARALENONE (also called F-2 toxin)

• Potent Non-steroidal oestrogenic mycotoxin.
• Produced by Fusarium roseum.
• Swine most commonly affected – called porcine vulvovaginitis/
Hyperestrogenic syndrome.
• Metabolites- α and β- zearalenols (α is most toxic, major in swine)
• β - zearalenol in cattle.
• Binds to cytosolic receptors for 17 β oestradiol.
• Clinical signs: in prepubertal gilts- hyperemia, enlargement of vulva.
• Hypertrophy of mammary glands& uterus.
• Heifers – vaginal discharge, Nymphomania, uterine hypertrophy,
abortions, atrophy of testes.
• PM findings: lesions found only in reproductive system.
• Treatment: Recovery of reproductive functions in 1-4wks after
intake of zearalenone stops.
• PGF2α administration.
• Dehydrated Alfalfa feed
 TRICHOTHECENES

• Produced by Fusarium, Trichothecium, Trichoderma,

cephalosporium.
• T-2 toxin is the most commonly found metabolite in Trichothecenes
class.
• Cats are more sensitive.
• Deoxynivalenol ( DON/ Vomitoxin) – another metabolite; vomition
due to its irritant nature. DAS (Diacetoxyscirpenol)
• Potent inhibitors of protein synthesis.
• Impairs ETC- cell death.
• Clinical signs: Acute toxicity – feed refusal, bloody diarrhoea,
hypothermia, haematuria, epistaxis.
• Tremors, seizures & paralysis in all species.
• In poultry- neurological effects with poor feathering.
• Chronic toxicity: ATA Toxicosis.(Alimentary Toxic Aleukia) in humans.
Petechial rashes on skin.
• In animals- infertility, poor hatchability.
• Yellow rain
• PM findings: haemorrhagic enteritis, decrease in spleen size in
chicks is seen only in T-2. not in any other mycotoxins.
• Analysis by TLC, HPLC techniques.
• Symptomatic treatment for GI signs, skin & oral lesions.
 ERGOT

• Produced by Claviceps purpurea

• Ergot alkaloids are derivatives of Lysergic acid.
• Alkaloids include Ergotamine, Ergometrine (Ergonovine) Ergocryptine,
Ergosine.
• Interacts with adrenergic, serotonergic & dopaminergic receptors.
• Stimulates vascular smooth muscle- vasoconstriction; acts on uterus.
• Toxic effect- due to continuous stimulation of adrenergic receptors in
vascular smooth muscle.
 Persistent vasoconstriction

damage to capillary endothelium

Reduced blood flow

Terminal necrosis of extremities due to thrombosis

Gangrene of extremities
• Ergotamine – potent to produce vasoconstriction
• Ergometrine/Ergonovine – potent oxytocic action
• CNS stimulation by interference with serotonin.
• Mimics action of Dopamine.
• Clinical signs:
• Acute/ Nervous Ergotism: recumbency, spasms, hyperexcitability,
ataxia, staggering gait.
• Tonic convulsions & posterior paralysis.
• Death due to anoxia during convulsions.
• Chronic/Gangrenous Ergotism: lameness, swelling of fetlock joint.
• Hooves & tail may slough off, prolonged constriction of arteries
result in ischemia & dry gangrene.
• PM findings: increase CSF, incomplete rigor.
• Ergot sclerotia may be found in GIT.
• Diagnosis:
• Clinical signs, necropsy findings, chemical analysis.
• Identification using TLC/GC/MS
• Treatment :
• Saline purgative ( Magnesium sulphate) to eliminate poison.
• Necrotic lesions- antibacterial agents.
• Treatment with Chlorpromazine/ Diazepam
• Animal should be kept warm to avoid cold induced vasoconstriction
in extremities.
 FESCUE

• Produced by Festuca species.

• Pregnant animals, particularly, mares are highly susceptible.
• Spontaneous abortions, stillbirths, retained placenta, agalactia.
• In cattle & sheep called Fescue summer toxicosis
• Ergovaline, (ergopeptide produced by Fescue) a potent
vasoconstrictor causes another syndrome in sheep & cattle called
Fescue foot.
 PATULIN
• Produced by Penicilium spp. and Aspergillus spp.
• Produced in apples, pears, grapes, barley, malt, rice
• Cattle have reportedly exhibited an ascending paralysis of motor
nerves with convulsions, excitement and cerebral haemorrhage.
• Lesions may include pulmonary and cerebral oedema, ascites,
congestion of liver, spleen, and kidneys in addition to the other
effects.
• It is an inhibitor of RNA polymerase.
Thank you