Potential developmental toxicity of anatoxin-a, a cyanobacterial toxin

Abstract

Some 2000 species of cyanobacteria (blue-green algae) occur globally in aquatic habitats. They are able to survive under a wide range of environmental conditions and some produce potent toxins. Toxin production is correlated with periods of rapid growth (blooms) and 25%-70% of blooms may be toxic. Anatoxin-a is an alkaloid neurotoxin that acts as a potent neuro-muscular blocking agent at the nicotinic receptor. Acute toxicity, following consumption of contaminated water, is characterized by rapid onset of paralysis, tremors, convulsions and death. Human exposures may occur from recreational water activities and dietary supplements, but are primarily through drinking water. The current studies were conducted to examine the effect of in utero exposure on postnatal viability, growth and neurodevelopment, to evaluate the potential of in vitro embryotoxicity, and to explore the synergistic relationship between anatoxin-a and the algal toxin microcystin-LR by the oral route. The results of preliminary studies on amphibian toxicity are also reported. Time-pregnant mice received 125 or 200 microg kg(-1) anatoxin-a by intraperitoneal injection on gestation days (GD) 8-12 or 13-17. Pup viability and weight were monitored over a 6-day period. Maternal toxicity (decreased motor activity) was observed at 200 microg kg(-1) in both treatment periods. There were no significant treatment-related effects on pup viability or weight on postnatal day (PND) 1 or 6. The GD 13-17 pups were evaluated on PND 6, 12 and 20 for standard markers of neurodevelopmental maturation (righting reflex, negative geotaxis and hanging grip time). No significant postnatal neurotoxicity was observed. In vitro developmental toxicity was evaluated in GD 8 mouse embryos exposed to 0.1-25 microm anatoxin-a for 26-28 h. Perturbations in mouse yolk sac vasculature were noted from the 1.0 microm concentration in the absence of significant embryonic dysmorphology. Potential algal toxin synergism was tested in mice receiving either 0, 500 or 1,000 microg kg(-1) microcystin-LR by gavage and approximately 50 min later receiving either 0, 500, 1,000 or 2,500 microg kg(-1) anatoxin-a by the same route. No deaths occurred at any dose and no definitive signs of intoxication were observed. Stages 17 and 25 toad embryos (Bufo arenarum) were exposed to 0.03-30.0 mg l(-1) of anatoxin-a for 10 days. Adverse effects included a dose-dependent transient narcosis, edema and loss of equilibrium. Most notable was the occurrence of 100% mortality at the high dose in both groups 6-13 days post-exposure. The observed delay between initial exposure and death is highly unusual for anatoxin-a.

Proteomic analysis of anatoxin-a acute toxicity in zebrafish reveals gender specific responses and additional mechanisms of cell stress

“…This results in convulsions and ultimately death by acute asphyxia (Dittmann and Wiegand, 2006). Other acute effects observed in vertebrates exposed to anatoxin-a include loss of coordination, decreased locomotor activity, muscle fasciculations, irregular breathing, tremors and altered gait (Carmichael et al, 1977;Rogers et al, 2005;Stolerman et al, 1992). In other experiments with carps and goldfish, behaviors such as rapid opercular movement, abnormal swimming (Osswald et al, 2007a) and muscle rigidity (Carmichael et al, 1975) were observed.…”

Review and analysis of occurrence, exposure and toxicity of cyanobacteria toxins in food

“…with 125, 200 µg/kg bw ATX (GD 8-12 or 13-17): no foetal malformation and reduced viability were observed even in the presence of maternal toxicity (at 200 µg/kg bw decrease of motor activity) (Rogers et al, 2005).…”

“…Yavasoglu et al, 2008 Anatoxin-a NOAEL 5 days 125 µg/kg bw/day Mouse. Maternal toxicity Rogers et al, 2005 Anatoxin-a NOAEL 21 days 16 µg/day Rat. Unbound NOAEL: no effect seen at the dose tested.…”

Experimental immunology Cytotoxic and immunotoxic effects of the mixture containing cyanotoxins on carp cells following in vitro exposure

“…Unfortunately, information about the potential synergistic effect of cyanotoxins is limited. Rogers et al [16] concluded that the synergistic effect of MC-LR and ATX-a was due to the different routes toxin uptake. The results of our previous in vitro and in vivo investigations also showed that the extract containing MCs or ATX-a Anna Rymuszka et al induced greater suppressive effects on essential functions of immune cells (ROS production, lymphocyte proliferation and cytokine production) than the pure toxins alone [10][11][12][13]15].…”