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VetBooks.ir Chapter 74

Tremorgenic Mycotoxins

Tim J. Evans and Ramesh C. Gupta

INTRODUCTION and a number of forages (e.g., legumes and grasses) con-
sumed by livestock species, and even food or beverage
Fungi belonging to the genera Penicillium, Aspergillus,
manufacturing byproducts, garbage and compost piles
Claviceps, and Neotyphodium can produce tremorgenic
can be sources of tremorgenic mycotoxins (Burrows and
mycotoxins, which are secondary fungal metabolites that
Tyrl, 2001; Boysen et al., 2002; Young et al., 2003).
elicit either intermittent or sustained tremors in vertebrate
Although there have been several human cases in which
species (Cole and Cox, 1981; Selala et al., 1989; Burrows
tremors and convulsions were attributed to consumption
and Tyrl, 2001). Over 20 mycotoxins containing a of mold-contaminated food containing penitrem A
tryptophan-derived indole moiety, including: penitrems,
(Gordon et al., 1993; Lewis et al., 2005), this chapter
roquefortine A, verruculogen, tryptoquivaline, aflatrem,
focuses on the toxicity of tremorgenic mycotoxins in
paspalinine, and paxilline as well as the paspalitrems and
animal species. Dogs, because of their relatively indis-
lolitrems (Table 74.1 and Fig. 74.1), have demonstrated
criminate appetite and frequently unsupervised roaming
tremorgenic potential in animals and humans (Selala
behavior, appear to be very susceptible to intoxication
et al., 1989; Burrows and Tyrl, 2001). Several other fun-
by penitrem A, as well as roquefortines (Boysen et al.,
gal metabolites, such as roquefortine C, paspaline, paspa-
2002; Young et al., 2003; Eriksen et al., 2010).
lacine, and cyclopiazonic, are chemically related to these
Mycotoxin-associated stagger syndromes in livestock,
mycotoxins but have been shown to not be tremorgenic
also described in the literature as “grass staggers” (not
(Knaus et al., 1994; Tiwary et al., 2009). With increased
to be confused with “grass staggers” or “grass tetany”
analytical capabilities, particularly the emergence of
related to hypomagnesemia), have most frequently occurred
advanced NMR, HPLC-MS, and LC-MS/MS spectro-
following the ingestion of endophyte (Neotyphodium lolii)
scopic methodologies, other “known” mycotoxins, with
infected perennial ryegrass (Lolium perenne) or consump-
both related and unrelated structures, such as ergonovine
tion of Dallisgrass (Paspalum dilatatum) or Bahiagrass
(ergometrine), ergine (lysergic acid amide), and patulin,
(Paspalum notatum) contaminated by sclerotia of
as well as “new” secondary fungal metabolites, like seco-
Claviceps paspali.
penitrem D, have been detected in samples associated
with clinical cases of tremorgenic syndromes and their
associated neurotoxicities (Sabater-Vilar et al., 2004; Tor BACKGROUND
et al., 2006; Uhlig et al., 2009; Moldes-Anaya et al., Penicillium-Associated Tremorgenic
2011). However, the precise roles of these detected fungal
metabolites in the pathogenesis of the observed tremor- Mycotoxins
genic syndromes are yet to be determined, and this task
Although a variety of different fungi synthesize
is complicated by the diversity of fungal matrices, the
indole diterpene mycotoxins having specific tremorgenic
propensity for myco- and phytotoxins to be present in
effects on the central nervous system (CNS), tremorgens
complex mixtures, and difficulties inherent to relating
produced by Penicillium spp. (especially penitrem A and
xenobiotic structure to function and concentration to
roquefortines) are the most commonly encountered of
biological relevance.
these mycotoxins. Penitrem A is a potent neurotoxin
Tremorgen-producing fungi grow on a wide variety of
which causes a syndrome characterized by sustained tre-
foodstuffs, including dairy or grain-containing products
mors and, at high doses, convulsions and death in labora-
intended for human consumption (e.g., cheeses and pas-
tory and farm animals (Wilson, 1971; Arp and Richard,
tas), stored grains and nuts (e.g., peanuts and walnuts)
1981; Peterson and Penny, 1982; Shreeve et al., 1983;
Veterinary Toxicology. DOI: http://dx.doi.org/10.1016/B978-0-12-811410-0.00074-X
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