Page 811 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

770 SECTION | XI Bacterial and Cyanobacterial Toxins

VetBooks.ir activated charcoal was used successfully to decontaminate et al., 2000; Gugger et al., 2005; Yang and Boyer, 2005;
Wood et al., 2007; Puschner et al., 2008, 2010).
drinking water (Warhurst et al., 1997), this decontamina-
Anatoxins are neurotoxins and can generally be divided
tion procedure was not protective in mice dosed with
microcystins (Mereish and Solow, 1989); no data are into anatoxin-a, homoanatoxin-a, and anatoxin-a(s).
available for other species. Anatoxin-a is a secondary amine and has been detected in
Diagnosis of microcystin toxicosis is corroborated by blooms worldwide. Homoanatoxin-a is a methyl deriva-
identification of microcystin-containing water in the envi- tive of anatoxin-a and has been identified in blooms in
ronment of the animal. Identification of algae material in Japan (Namikoshi et al., 2004), Ireland (Furey et al.,
water and gastric contents is an important component of 2003), Sweden (Skulberg et al., 1992), and New Zealand
the diagnostic workup but does not confirm intoxication. (Wood et al., 2007). Anatoxin-a(s) is a unique N-hydroxy-
As described previously, the toxicity of the cyanobacteria guanidine methyl phosphate ester that has been detected
is strain specific, and morphological observations alone in the Americas (Monserrat et al., 2001) and Europe
cannot predict the hazard level, but polymerase chain (Henriksen et al., 1997). Commercially available blue-
reaction detection of microcystin-producing genes can green algae dietary supplements also represent a potential
help identify a potentially culpable species. Detection of source (Rella ´n et al., 2009).
microcystins in gastric contents is confirmatory, but these
tests are not routinely available at diagnostic laboratories Pharmacokinetics/Toxicokinetics
and are limited to a few structural variants. In the past,
the mouse bioassay was used to determine the toxicity of Definite data on the toxicokinetics of anatoxin-a,
crude algal biomass in suspicious blue-green algae poi- homoanatoxin-a, and anatoxin-a(s) have not been estab-
sonings. Although many assays are available to analyze lished. Based on the rapid onset of clinical signs after oral
water samples for microcystins (Maizels and Budde, exposure, rapid absorption of the toxins is suspected.
2004; McElhiney and Lawton, 2005; Frias et al., 2006), Anatoxin-a has been detected in the urine and bile of a
there are only limited methods available to reliably and poisoned dog, confirming that anatoxin-a is, at least in
accurately detect microcystins in biological specimens part, excreted unchanged in urine and bile (Puschner
collected from animals suspected to have died from et al., 2010).
microcystin intoxication (Bogialli et al., 2005; Karlsson
et al., 2005b; Chen et al., 2009). An electrospray ioniza-
Mechanism of Action
tion liquid chromatography mass spectrometry method
has been developed to determine the bound microcystin Anatoxin-a is a potent cholinergic agonist at nicotinic ace-
concentrations in animal tissues, which provides an esti- tylcholine receptors (nAChRs) in neurons and at neuro-
mate of the total microcystin burden in exposed animals muscular junctions (NMJs) (Thomas et al., 1993).
(Ott and Carmichael, 2006). Anatoxin-a has two enantiomers, with (1)anatoxin-a hav-
Differential diagnoses in animals with a clinical pre- ing a higher binding affinity than the (2) form (Spivak
sentation of liver failure include other toxic ingestions, et al., 1980; Zhang and Nordberg, 1993). Compared to
such as amanitins, cocklebur, cycad palm, aflatoxin, xyli- nicotine, anatoxin-a is approximately 20 times more potent
tol, certain heavy metals, and acetaminophen overdose. than acetylcholine. After continuous electrical stimulation
Careful evaluation of the history, feed, and environment at the NMJs, a nerve block may follow and result in death
of the animal can help eliminate most of the toxicant dif- due to respiratory paralysis. Furthermore, anatoxin-a has
ferentials on the list. modulatory action at presynaptic nAChRs, which can lead
to dopamine as well as noradrenaline release (Barik and
Wonnacott, 2006; Campos et al., 2010). Clinical signs of
ANATOXINS
anatoxin-a poisoning include a rapid onset of rigidity and
Anatoxins are mainly produced by cyanobacteria in the muscle tremors followed by convulsions, paralysis, respi-
Anabaena genus (Beltran and Neilan, 2000) but also by ratory failure, cyanosis, and death. Death usually occurs
other genera, such as Plantkothrix, Oscillatoria, within minutes to a few hours. Anatoxin-a poisonings
Microcystis, Aphanizomenon, Cylindrospermum, and have been reported in dogs in Europe (Edwards et al.,
Phormidium. Only few data exist about factors resulting 1992; Gunn et al., 1992; James et al., 1997; Gugger et al.,
in anatoxin-a production (Me ´jean et al., 2014; Wood 2005) and the United States (Puschner et al., 2008, 2010).
et al., 2017) and indicate the impact of multiple physico- Anatoxin-a is also considered a contributing factor in the
chemical variables. Reports of anatoxin poisoning are less deaths of Lesser Flamingos in Kenya (Krienitz et al.,
frequent than those of microcystin toxicosis; however, 2003). Homoanatoxin-a is a methyl derivate of anatoxin-a
poisoning has occurred worldwide (Edwards et al., 1992; with similar pharmacological and toxicological properties
Gunn et al., 1992; Beltran and Neilan, 2000; Fromme (Wonnacott et al., 1992), and it has been implicated in