Anatoxin Effects Whole Body Plethysmography Outcomes In Mice
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Anatoxin-a is a neurotoxic alkaloid produced by several species of cyanobacteria, most notably Dolichospermum flos-aquae and the benthic Microcoleus species. Anatoxin-a has been referred to as the very fast death factor due to the remarkably quick onset of symptoms including decrease in locomotor activity, muscle paralysis, and respiratory arrest leading to death. Muscular and respiratory paralysis has been recorded as rapidly as 2-6 minutes after exposure. While the time between dosing and onset of symptoms are well recorded, the toxicokinetics of anatoxin-a are under-studied. We conducted whole-body plethysmography tests on mice orally exposed to anatoxin-a to better understand respiratory suppression, a parameter that will inform toxicokinetic models.
Mice can freely move in the Emka whole body plethysmography (WBP) chamber. After a 20-minute baseline plethysmography data collection period, we exposed male and female mice to oral doses of 0, 2, or 4 mg/kg of anatoxin-a. Mice were placed back into the whole-body plethysmography chamber for a 60-minute recording session post dosing. Serum samples were collected at 60, 90, and 180 minutes. Mice were euthanized and necropsied at 360 minutes. Data were analyzed with linear mixed models. Tidal volume, inspiratory time, expiratory time, peak inspiratory flow, peak expiratory flow, relaxation time, minute-volume, breathing frequency, enhanced pause (an indicator of airway resistance), and number of beats all showed significant dose effects. These results will be incorporated into a toxicokinetic model which will be vital in informing future studies as well as risk assessments for anatoxin-a.