Page 1064 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

996 SECTION | XV Mycotoxins

VetBooks.ir which, depending on pH, animal species, and physiological
state, can involve both passive and active processes.
Strickland et al., 2011) reported that most of the gastroin-
testinal absorption of the ergopeptine alkaloids takes place
in the small intestine. Concentrations of ergovaline are
very low in endophytes (parts per billion or low parts per
million), so they are rarely detected in animal tissue or
fluids. Ergovaline is difficult to detect in rumen fluid and
is metabolized by rumen microbes to lysergic acid. Oliver
(1997) found that 50% 60% ofingestedergovalineisin
the abomasal contents, and minimal amounts of ergovaline
remain in the ileal contents or feces. Ergovaline is also
believed to be metabolized in the liver by cytochrome
P450 3A4. Intravenous injection of several ergopeptides in
calves documented a distribution and tissue equilibrium
phase in serum lasting approximately 1 h (Moubarak et al.,
1996), followed by an elimination phase with a half-life of
approximately 20 30 min.
Urine, bile, feces, and to a much lesser extent milk are
the primary routes of elimination and excretion for ergot
alkaloids (Evans et al., 2004a, 2012; Strickland et al.,
2011). In cattle, 96% of the ergot metabolites are found in
urine. Ergot alkaloids are detected in urine within 12 h of
exposure to fescue endophytes and are maximal within
24 h. After removal from a fescue pasture, ergot metabo-
FIGURE 70.1 Claviceps purpurea fungal sclerotia growing on barley.
Wikipedia.Com. lites are gone within 48 h from the urine of cattle.
Injected intravenously, ergopeptine alkaloids are rapidly
cleared from the blood by the liver (Cheeke, 1998) and
identified in cereal grains. Compared to sclerotia in oats
excreted in the bile.
or barley, the sclerotia are quite small in grass seeds such
as Bahia grass (Paspalum notatum). Sclerotia fall to the
ground to over winter and later complete the fungal life MECHANISM OF ACTION
cycle by germinating and producing ascospores capable
Ergot alkaloids have structures similar to the biogenic
of infecting the ovary of developing seeds.
amines norepinephrine, serotonin, and dopamine.
Alkaloids from C. purpurea are among the most
Vasoconstriction is produced by an agonist activity, and
important natural products used by the pharmaceutical
this effect varies with different vascular beds. Other
industry. Prior to the industrial cultivation of C. purpurea
effects include hyperthermia and uterine stimulation. The
in the pure culture, ergot was grown as a crop on rye
alkaloids are antagonistic to dopamime at D 1 vasodilatory
under field conditions for use in the manufacture of
receptors (Cross et al., 1995). Dopaminergic activity at
important medicinal drugs. Synthesized ergot alkaloids
D 2 receptors causes inhibition of prolactin secretion
have a variety of uses in human and veterinary medicine.
(Goldstein et al., 1980). Ergovaline is a dopamine D 2
Chemical structures of some of the ergot alkaloids are
receptor agonist (Oliver, 1997). Ergopeptine alkaloids
shown in Fig. 70.2. Unlike C. purpurea, N. coenophialum
have a 10-fold greater affinity for dopamine D 2 receptor
produces multiple classes of toxins, including ergot alka-
binding than do ergoline alkaloids (Larson, 1997).
loids, loline alkaloids, and peramine.
Dopamine agonists mimic the endogenous tonic inhibition
of pituitary lactotropes by dopamine and inhibit prolactin
secretion by the anterior pituitary. Prolactin inhibition is
PHARMACOKINETICS/TOXICOKINETICS
one of the most consistent problems observed in multiple
Ergot alkaloids responsible for most clinical signs and species exposed experimentally to ergopeptine alkaloids
lesions are of the ergopeptine class including ergotamine, and/or those experiencing clinical fescue toxicosis. In
ergocristine, ergosine, ergocornine, ergocryptine, and ergo- essence, this effect of ergovaline and other ergot alkaloids
valine (Burrows and Tyrl, 2001; Cheeke, 1998; Carson, is an exquisite, naturally occurring example of “endocrine
1999, Evans et al., 2004a,b). The rumen and small intestine disruption” and is a sensitive biomarker for exposure to
are most likely the principal sites of ergot alkaloid uptake, these compounds (Evans et al., 2012). Lower prolactin