VPT621 ASSIGNMENT

NEPHROTOXIC M
YCOTOXINS
BENCY ELSA JOHNSON
M-6183
VETERINARY PHARMACOLOGY & TOXICOLOGY
ICAR-INDIAN VETERINARY RESEARCH INSTITUTE
 OCHRATOXINS
Aspergillus ochraceus & Penici
llium viridicatum
Infest barley, corn, wheat, rice,
rye oats, green coffee beans an
d pea nuts
Produced during long term sto
rage
Stable and slowly decomposed
during prolonged storage
Renal damage in affected anim
als
Cause syndrome- mold nephro
sis or mycotoxic nephropathy
 CHEMISTRY

Group of nine isocoumarin derivatives linked with p

henylalanine by amide bond
Most common & toxic- ochratoxin A
Ochratoxin A consists of a polyketide derived dihydr
oiso-coumarin moiety linked through 12-carboxy gro
up to phenylalanine
Ochratoxin B- absence of chlorine atom is the only di
fference
Others are ochratoxin-C, α, β
 PROPERTIES

Colourless crysalline compound, exhibiting blue fluo

rescence under UV light
For growth optimum moisture content is > 16% & rel
ative humidity> 85%
Relative temperature- 12-15°C
Survives most food processing to an extent
Can be stored in ethanol under refrigeration and pro
tected from light
 TOXICOKINETICS
Absorbed from GI tract an
d distributed mainly to liv
er and kidneys

Ochratoxin A accumulates
in body tissues and fat of p
igs and poultry

Disappears from muscles a

nd fat of affected pigs after
2weeks ad from liver and k
idneys after 3-4 weeks

T1/2 – 3-5 days, also minu

te quantities in kidneys ev
en after 30 days

Found to cross placental b

arrier
 SPECIES AFFECTED

Pigs, poultry, goats, horse, cattle and mice are affec

ted
Pigs are often involved
Birds - most susceptible, cattle- less susceptible
acute LD50 – dogs are most susceptible sp.
 - 1-5 ppm in birds, swine
 -59ppm in mice
 MOA
Ochratoxin A - hydrolysed to non-toxic ochratoxin al
pha
These two Inhibits mitochondrial respiration & oxid
ative phosphorylation, thus reduce ATP levels
Also interfere with functioning of mRNAs that are in
volved in the synthesis of various c-AMP mediated e
nzymes like phosphoenol pyruvate carboxykinase,ot
her enzymes of gluconeogenesis pathway
Cause increase in generation of free radicals via cyto
chrome P-450 reductase metabolism
Cause tubular epithelial cell damage
Impairs proximal tubular func
tion
Decrease metabolic clearance,
urine concentration ability
Inhibit anion transport and ca
use release of renal brush bor
der enzymes(leucine aminope
ptidase)
Periglomerular and interstitial
fibrosis, tubular atrophy
Residues detected as carryove
r in pigs and poultry meats tha
t may produce harmful effects
in humans
 CLINICAL SIGNS

Anorexia, depression, fatigue, abdominal pain, polyd

ipsia, polyuria, weight loss and severe anemia follow
ed by renal damage
Death due to uremia
In poultry:
Listlessness, reduced egg production, feed intake
Ataxia, prostration and death
Enlarged greyish kidney
Hypochromic microcytic anemia
Immunosuppressant
Reduce sperm quality in board
Cause fetal death & resorption, abortion in sow
Teratogenicity, carcinogenicity and haemorrhages in
natural or experimental toxicosis
Not mutagenic but induce hepatoma & renal adenom
as in mice
 DIAGNOSIS

History
Clinical signs, lesions
Laboratory analysis
TLC or HPLC- chemical analysis
Elevated BUN and serum creatinine levels – blood a
nalysis
Also detected in renal, hepatic and adipose tissues
 TREATMENT

No specific antidote available

Activated charcoal to reduce absorption
Removal of offending feed
Restriction of intake of protein in diet
Supportive therapy
PREVENTION
 Don’t use feed if ochratoxin level is more than 10ppb
Proper harvesting and drying of feed before storage
 CITRININ
Substituted benzopyran c
arboxylic acid
Toxigenic fungi Penicilliu
m citrinum, P. Viridicatu
m,P.palitans, A.ochraceu
s etc
Grow on feeds like barley
, wheat, rye and corn
Found in combination wi
th ochratoxin
Produces mycotoxic nephropathy or mold nephrosis
in livestock
Affects mainly cattle, pig and poultry
Also produce pyrexia-pruritis- haemorrhagic diathes
is in cattle
On feeding moldy citrus pulp containing citrinin@3
0-40ppb
MoA is similar to ochratoxin A
Causes kidney damage and mild liver damage in the f
orm of fatty infiltration
Vasodilation, bronchoconstriction, and increased mu
scular tone also observed
 In sub acute toxicity in chicks- diarrhoea, polydipsia
, harm in jejunum, mottled liver, enlarged kidneys, r
educed weight gain
 HISTOPATHOLOGICAL FINDINGS

Low grade and interstiti

al nephritis
Depletion of lymphoid t
issues
Wide spread petechial h
aemorrhages in body &
tissues
Centrilobular necrosis o
f hepatocytes
 TREATMENT

 No specific treatment
 withdrawal of offending feed
Supportive therapy
 OOSPOREIN

Oospora colorans, chaetomium so.,

Acremonium sp. and Beauveria bassi
ana
Substituted bisbenzoquinone
Interfere with excretion of uric acid a
nd produces nephrotic gout in poultr
y
No specific treatment available
 PREVENTION

Removal of mycotoxins from contaminated commodities, incl

uding physical separation, extraction with solvents and adsor
ption
Detoxification by physical, chemical and biological methods
Physical methods- thermal processing (cooking, boiling, bakin
g, frying, roasting, microwave heating, extrusion) and irradiati
on
Chemical methods- treatment with acids, bases, oxidizing age
nts, reducing agents, chlorinating agents, and miscellaneous r
eagents
Biological methods- enzymatic degradation, modifying toxins,
bacterial degradation of toxins
 REFERENCES

Garg S. K.2002. veterinary toxicologyCBS Publishers

& Distributors pvt.Lmt
Sandhu H. S., Brar. R. S.2000. Textbook of veterinar
y toxicology. Kalyani publishers, Ludhiana-NewDelhi
Zaki. M. M., El-Midany. S. A., Shaheen. H. M and Ri
zzi. L.2012. Mycotoxins in animals: Occurrence, effec
ts, prevention and management. J. Toxicol. Environ.
Health Sci. Vol. 4(1), pp. 13-28
THANK YOU…