Page 1074 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

1006 SECTION | XV Mycotoxins

VetBooks.ir messenger that inhibits L-type calcium channels in myo- leukoencephalomalacia have histologic evidence of
cerebral edema in the brain. Another study reported that
cardial cells, thereby decreasing sarcoplasmic reticulum
21
21
Ca -induced Ca -release and cardiac contractility
fumonisin-treated horses also have elevated protein, albu-
(McDonough et al., 1994; Webster et al., 1994). As sphin- min, and IgG levels in cerebrospinal fluid samples
gosine concentrations begin to increase in pigs that (Foreman et al., 2004). Taken together, these findings
consume fumonisin, myocardial calcium channels are indicate that fumonisin toxicity in horses is associated
blocked and contractility begins to decrease with the development of vasogenic cerebral edema as a
(Constable et al., 2000; Smith et al., 2000). Ultimately direct result of increased blood brain barrier permeabil-
this decrease in cardiac contractility causes acute left ven- ity. Horses are dependent on autoregulation of cerebral
tricular failure and pulmonary edema (Fig. 71.3). blood flow when they lower their head to graze. Because
The mechanism of ELEM may also be a direct result of gravitational forces, distal carotid artery pressure can
of fumonisin-induced increases in sphingosine concentra- increase tremendously when the animal bends to eat or
tions. Cardiovascular dysfunction following fumonisin drink. However, this rise in carotid pressure does not cre-
administration in horses has been demonstrated (Smith ate a significant increase in cerebral blood flow due the
et al., 2002). This study reported an association between constriction and dilation of cerebral arterioles, which
neurologic signs, increased serum and myocardial sphin- maintain normal cerebral blood pressures (Faraci and
gosine concentrations, and cardiovascular depression in Heistad, 1990). It has been shown that L-type calcium
fumonisin-treated horses. At necropsy, horses with channels are the primary mediators of vascular tone in
these cerebral arterioles (Michelakis et al., 1994).
Therefore, it has been hypothesized that fumonisin-
Fumonism consumption induced increases in sphingosine concentrations inhibit
the calcium channels in cerebral arterioles leading to the
inability to maintain normal cerebral blood pressure and
vasogenic cerebral edema. This hypothesis requires
Inhibits sphingosine N-acyltransferase
further research to be proven definitively.

TOXICITY
↑ tissue (sphingosine)
Fumonisin has been shown to cause liver damage in mul-
tiple species including pigs, horses, cattle, rabbits, and
2+
Inhibition of L-type Ca channel primates (Gumprecht et al., 1995; Haschek et al., 1992;
Jaskiewicz et al., 1987; Osweiler et al., 1993; Ross et al.,
1993; Voss et al., 1989) as well as species-specific target
Myocardium organ toxicity, such as lung in pigs (Haschek et al.,
1992), brain in horses (Ross et al., 1993), kidney in rats,
rabbits, and sheep (Edrington et al., 1995; Gumprecht
2+
↓ sarcoplasmic reticulum Ca -induced et al., 1995; Voss et al., 1989), and esophagus in rats and
2+
Ca -release pigs (Casteel et al., 1993; Lim et al., 1996). This chapter
will focus on fumonisin toxicity in pigs and horses since
they exhibit the most common clinical poisonings dealt
↓ Myocardial contractility with in veterinary medicine, however cattle and poultry
will be briefly discussed.

Left-sided heart failure Spontaneous and Experimental Fumonisin
Toxicosis in Swine

In early research prior to the initial isolation and characteri-
Pulmonary edema
zation of fumonisins, F. verticillioides culture material was
reported toxic to swine (Kriek et al., 1981). In that experi-
FIGURE 71.3 Mechanism of fumonisin-induced pulmonary edema in ment, three pigs were fed F. verticillioides culture material
swine. Fumonisin inhibition results in increased tissue sphingosine and grown on corn. Two of the three pigs fed the culture mate-
sphinganine concentrations. The increased sphingosine concentrations
inhibit the L-type Ca 21 channels of cardiac myocytes resulting in rial in this study died within 5 days of pulmonary edema.
decreased myocardial contractility. This decrease in contractility results The third pig was fed culture material for 89 days and was
in acute left-sided heart failure and pulmonary edema. then killed following a period of feed refusal.