Page 1088 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

1020 SECTION | XV Mycotoxins

VetBooks.ir (reviewed in Gupta et al., 2017). Absorption of OTA also
takes place in the duodenum and jejunum, is involved in
enterohepatic circulation and its biliary excretion is very
efficient (Kumagai and Aibara, 1982; Kumagai, 1988).
OTA is distributed to various organs, mainly to the kid-
neys. Liver, muscle and fat contain lower concentrations.
Following oral administration, the overall percentage of
OTA absorption is found to be 66% in pigs, 56% in rats,
56% in rabbits and 40% in chickens (Suzuki et al., 1977;
Galtier et al., 1981). After a single oral dose, the maxi-
mum concentrations of OTA are found within 10 48 h in
pigs and rats (Galtier et al., 1979, 1981), 2 4 h in calves
(Sreemannarayana et al., 1988), after 1 h in rabbits and
after 0.33 h in chickens (Galtier et al., 1981). Maximum
tissue concentrations in rat tissues occur within 48 h.
OTA has shown a high binding affinity for plasma
proteins. Vettorazzi et al. (2009) demonstrated that male
rats had lower OTA bioavailability than females due to
the male-specific protein alpha-2u-globulin. OTA was
found in decreasing order of concentrations in kid-
ney , liver , fat , muscle. The serum half-life of OTA is
long and varies widely among species, e.g., 24 39 h in
mice, 55 120 h in rats, 6.7 h in quail, 510 h in Macaca
mulata monkeys (Hagelberg et al., 1989), 72 120 h in
pigs, 4.1 h in chicken (Galtier et al., 1981) and 840 h in a
FIGURE 72.1 Chemical structures of ochratoxins. human (Benford et al., 2001). Fasting has been shown to
increase the rate of OTA absorption and its maximum
plasma concentrations in rats (Vettorazzi et al., 2009).
Toxicokinetics of OTA in pigs revealed that the kidney
is generally the most heavily contaminated tissue and that
levels in the blood are about fivefold greater than in the
kidney. Krog et al. (1976) illustrated that if the level of
OTA in swine kidney is 12.1 ng/g (resulting from about
1000 ng/g in the feed), its levels would be 7.8 ng/g in the
liver, 4.2 ng/g in the muscle and 2.8 ng/g in adipose tissue.
FIGURE 72.2 Chemical structure of citrinin.
OTA in ruminants is usually hydrolyzed in the forestomach
by protozoans and bacterial enzymes, and consequently
clematitis, which grows as a weed in the wheat fields of
little OTA is found in the tissues (Hult et al., 1976).
the BEN region, and nephropathy (Stiborova ´ et al., 2016).
In the context of metabolism, various tissues of all
Co-occurrence of citrinin with OTA has been implicated
species that are examined, OTA is hydrolyzed to ochra-
in nephropathy of pigs in Denmark, Sweden, Norway and
toxin alpha, which is the major metabolite (reviewed in
Ireland. Citrinin and OTA are also involved in avian
Gupta et al., 2017). This detoxication process also takes
nephropathies. Residues of OTA have been detected in
place in the cecum of rats and is facilitated by bacterial
the tissues of pigs in slaughterhouses, and it has been
microflora (Galtier, 1978). The enzymes responsible for
shown, under experimental conditions, that residues can
hydrolysis to ochratoxin alpha in cows, sheep and rodents
still be detected in tissues 1 month after the end of expo-
are carboxypeptidase A and chymotrypsin. Suzuki et al.
sure. Due to the long half-life of OTA in feed and biologi-
(1977) demonstrated that the rat tissue homogenate of the
cal systems, serious concerns have been raised about duodenum, ileum and pancreas also has a high activity of
animal health as well as the human consumption of meat. these enzymes to catalyze this reaction. Activity of these
enzymes in liver and kidney are low. Studies in mice sug-
gest that OTA circulates from the liver into the bile and
TOXICOKINETICS
into the intestine, where it is hydrolyzed to ochratoxin
OTA is absorbed from the stomach because of its lipid alpha (Moroi et al., 1985). About 25% 27% of OTA,
soluble, nonionized and acidic properties (pK a 5 7.1) given either i.p. or orally to rats, was found as ochratoxin