Page 1106 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

1038 SECTION | XV Mycotoxins

VetBooks.ir (Hocking et al., 1988). In a histopathological study in exception of penitrem A, exhibited a certain degree of
genotoxicity. Verrucosidin appeared to have the highest
rats, Breton et al. (1998) revealed that penitrem
positive
testing
in
potential,
toxic
A induced dose-related injuries in the cerebellum with
assays.
both
massive degeneration of Purkinje cells and a significant Verruculogen tested positive in the Salmonella/mammalian-
vacuolization within the molecular layer. In one instance microsome assay, and paxilline and fumitremorgen
of neurological disorders in dairy cattle associated with B caused DNA damage in human lymphocytes.
Aspergillus clavatus-contaminated beer residues, neuronal
degeneration was observed within the brainstem and ven- Acute Toxicity
tral spinal cord, but no analyses for tremorgenic mycotox-
ins were performed in order to confirm a causal Acute toxicity data are available for only few of the tre-
relationship between any tremorgens and the observed morgenic mycotoxins. It should be noted that the relative
pathology (Loretti et al., 2003). doses resulting in lethality in different species might not
necessarily be reflective of the relative tremorgenic poten-
tials of these mycotoxins. The LD 50 of penitrem A in
Peripheral Effects
mice is 15 19 mg/kg, IP (Ling et al., 1979). The LD 50 of
Tremorgenic mycotoxins have also been studied for verruculogen is reported to be 15.2 mg/kg, IP, and
peripheral effects (Cotton et al., 1997; McLeay et al., 266 mg/kg, following oral exposure, in the chicken, with
1999; Dalziel et al., 2005). The tremorgenic mycotoxins, the corresponding LD 50 values in mice being 2.4 mg/kg,
such as penitrem A, paxilline, and lolitrem B can have IP, and 127 mg/kg, following oral exposure. The LD 50
profound effects on electromyographic (EMG) activity of value of penitrem A in mice is 15 19 mg/kg, IP (Ling
smooth muscle of the reticulorumen in conscious sheep, et al., 1979). Dogs receiving penitrem A (0.5 mg/kg, IP)
with a time course of action similar to their respective showed tremors within 10 min, followed by clonic or
characteristic effects on the induction (1 2, 15 20, and tonic convulsions (Hayes et al., 1976). Dose-related liver
20 30 min) and the duration (1 2, 1 2, and 8 12 h) of damage varied from massive necrosis in dogs receiving
tremors. Response to penitrem A revealed a greater sensi- 2.5 5.0 mg/kg of penitrem A to no pathologic alterations
tivity of smooth muscle than skeletal muscle. The excit- in dogs given 0.125 mg/kg.
atory local effects were partially blocked by atropine,
indicating that stimulation of muscarinic cholinergic Potential Interactions
receptors was involved. Increased local activity may
mediate a reflex inhibition of cyclical contractions. In previous studies, concurrent production of roquefor-
However, a nontremorgenic isomer of lolitrem B (31-epi- tines and penitrem A by various species of Penicillium
lolitrem B) had no effect on the reticulorumen. The inten- (e.g., P. crustosum, P. cyclopium Westling, and P. com-
sity and duration of the effects of lolitrem B (up to 12 h) mune) was demonstrated in culture extracts (Vesonder
indicate that severe disruption of digestion may occur in et al., 1980; Wagener et al., 1980; Kyriakidis et al., 1981;
animals grazing N. lolii-infected pasture. Moderately Mantle et al., 1983). Braselton and Rumler (1996) first
severe muscle contractions, traumatic events secondary to reported the concurrent presence of both tremorgenic
ataxia, and prolonged recumbency, especially in large ani- mycotoxins in naturally occurring field cases of canine
mals, can potentially result in muscle damage following intoxication and raised the issue of the potential synergis-
suspected exposure to tremogenic mycotoxins, but tic interactions between these tremorgens. In two recent
directly myotoxic effects of some mycotoxins cannot be cases, both Boysen et al. (2002) and Young et al. (2003)
ruled out (Loretti et al., 2003). diagnosed concurrent intoxication with penitrem A and
roquefortines in several dogs. Given that roquefortines
and penitrem A can have similar mechanisms of action,
Genotoxicity
there might be the potential for some synergism between
Five tremorgenic mycotoxins (fumitremorgen B, paxil- the two tremorgenic mycotoxins or at least a reduction
line, penitrem A, verruculogen, and verrucosidin), which in the amount of ingested contaminated material required
have been associated with molds found in fermented for the onset of clinical signs. Likewise, it would seem
meats, were assessed for genotoxicity (Sabater-Vilar logical in instances of “grass staggers” that a greater con-
et al., 2003). The mycotoxins were tested in two short- centration of multiple, potential tremorgenic mycotoxins
term in vitro assays using different genotoxic end points, in contaminated forages would increase the likelihood
in different phylogenetic systems, with the use of and, potentially, the severity of observed intoxications.
mammalian-microsome assay and the single-cell gel elec- However, the behavior of mycotoxins, especially those
trophoresis assay of human lymphocytes. The findings interacting with specific receptors, might not be
revealed that all of the tested mycotoxins, with the predictable in mixtures, and the paralytic tremorgen,