Page 1091 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Ochratoxins and Citrinin Chapter | 72 1023

VetBooks.ir had diarrhea and nasal discharge and died before the end cells, primarily in the straight segment of the proximal
tubules. Dogs given 10 mg/kg citrinin had similar changes
of the study. Increased relative weights of kidneys, heart
in the distal tubules and collecting ducts. Dogs given
and brain, thymus atrophy, forestomach necrosis, and/or
hyperplasia, and hemorrhage of adrenal glands were seen combined doses of citrinin and OTA had degeneration
at the two higher doses. Bone marrow hyperplasia and and necrosis in proximal and distal tubules, and in thin
nephropathy were seen at all doses, involving renal tubu- segments and the collecting ducts and ulceration of the
lar degenerative and regenerative changes (NTP, 1989). mucosa of the intestine.
OTA has been shown to produce nephrotoxic effects In experimental studies, dogs given citrinin showed
in all animal species examined, with the exception of serous nasal discharge and lacrimation (Carlton et al.,
adult ruminants (Pohland et al., 1992). The nephrotoxic 1974; Kitchen et al., 1977a,b). It is important to mention
potential of OTA is well documented from all experimen- that citrinin is a very strong emetic in dogs, which is a
tal studies, with a feed level of 200 ppb causing nephropa- protective mechanism in this species. Therefore, it is very
thy in pigs and rats. Evidence strongly supports that OTA unlikely that dogs will be poisoned by citrinin alone
is involved in porcine nephropathy, which is characterized because high amounts of this mycotoxin will induce eme-
by degeneration of the proximal tubules, atrophy of the sis and feed refusal.
tubular epithelium, interstitial fibrosis in the renal cortex Chickens, turkeys and ducklings are all susceptible to
and hyalinized glomeruli. Field cases of OTA-induced OTA and it appears that OTA-contaminated feed has a
nephropathy in farm animals have long been recognized. major economic impact on the poultry industry (Stoev,
Benford et al. (2001) suggested that the adverse effect at 2010a,b). Field cases of OTA-induced nephropathy are
the lowest effective dose in several mammalian species is regularly encountered in poultry. Clinical signs of ochra-
nephrotoxicity. Citrinin is also nephrotoxic, but it is ten toxicosis include retarded growth rate, reduction in weight
times less toxic than OTA. gain, poor feed conversion, reduced egg production, poor
In a series of experiments, sows were given feed egg shell quality, nephrotoxicity/nephropathy, and mortal-
containing OTA at a concentration of 0.2, 1, or 5 mg/kg ity. Feed refusal has been observed in turkeys.
(equivalent to 0.008, 0.04 and 0.2 mg/kg body weight/ In chickens, OTA at a dose rate of 3.6 mg/kg can
day), for a period of 5 days, 8 or 12 weeks, or up to 2 cause 5% mortality. OTB at a dose rate of 54 mg/kg
years. Decreased renal function, nephropathy and reduced causes lowered growth rate, edema of visceral organs, and
renal enzyme activity were observed. Progressive accumulation of uric acid in kidneys, liver, heart and
nephropathy but no renal failure was seen in pigs given spleen. These mycotoxins induce suppression of blood
feed containing 1 mg/kg for 2 years (Krog et al., 1976; formation in bone marrow, and lymph formation in spleen
Elling et al., 1985). and bursa of fabricus. The highest toxicity of OTA is
Beagle dogs receiving OTA in capsule form at a dose found to be in broiler chickens. OTA given to broiler
of 0.1 or 0.2 mg/kg body weight/day for 14 days showed chickens at a dietary concentration of 4 mg/kg for 2
tubular necrosis and ultrastructural changes in the proximal months caused a 42% mortality (Gibson et al., 1990).
tubules at all doses. Necrosis of lymphoid tissues of the This toxin is involved in reduced growth rate at 5 ppm,
thymus and tonsils was also seen at all doses (Kitchen high mortality rate at 4 8 ppm and cessation of egg pro-
et al., 1977a,b,c). In another set of experiments, young bea- duction at 4 ppm. In a recent study, Stoev (2010b) demon-
gle dogs were given OTA and citrinin separately and com- strated that OTA-induced suppressive effect on egg
bined for 14 days (Kitchen et al., 1977b). OTA was production in laying hens, and this effect was partially
administered by capsule at 0.1 and 0.2 mg/kg; and citrinin protected by some feed additives (sesame seed and water
(5 and 10 mg/kg) dissolved in ethanol was given by i.p. extract of artichoke).
injection. Clinical signs of toxicosis with 10 mg/kg citrinin In chickens, nephrotoxicity and hepatotoxicity occur
and the higher combined doses included anorexia, retching, at dietary levels of 250 μg/g of citrinin with liver and
tenesmus, weight loss, prostration and death. Severity of kidney enlargements of 11% and 22%, respectively.
the clinical disease and mortality were increased when the Necropsy of affected birds revealed the presence of pale
mycotoxins were combined, which indicated synergism. and swollen kidneys (Wyatt, 1979). Citrinin is at least ten
The clinicopathological abnormalities reflected renal dam- times less nephrotoxic than OTA.
age, cellular and granular casts, and ketones as well as pro- Griffiths and Done (1991) described an outbreak of
tein and glucose in the urine of dogs given large doses of citrinin toxicosis in a herd of cows that ingested citrus
citrinin alone or combination with OTA. In pathological pulp (visibly moldy) pellets that contained 30 40 ppb
studies, these authors found gross lesions, such as focal citrinin. Affected cows showed signs of pruritis, pyrexia,
peritonitis and intestinal intussusceptions with citrinin. and hemorrhagic syndrome. Signs of the syndrome
Changes in the kidneys of dogs given OTA were degenera- occurred within 3 days of ingesting the citrus pulp, which
tion and necrosis with desquamation of tubular epithelial was fed for 21 days. Five calves whose dams had been