Comparative pathology and diagnosis of domoic acid toxicity.

摘要

Domoic acid (DA) is an excitatory neurotoxic analog of glutamate produced by diatoms. Seafood contamination has caused human deaths and mass mortality in marine mammals and sea birds. Studies of both naturally occurring and experimental DA toxicity were performed to facilitate the diagnosis of DA toxicity in marine wildlife.; California sea lions (Zalophus californianus) involved in DA induced mass strandings were examined. Animals died one day to ten months after DA induced seizures. Acute gross findings consisted of myocardial pallor, bronchopneumonia, and uterine catastrophe. Bilateral hippocampal atrophy was noted chronically. Microscopically, widespread limbic system injury was present.; The pathologic effects and pharmacokinetics of DA in pigeons and mallard ducks was studied. The intracoelomic LD₅₀ (lethal dose) (mg/kg) was 0.9 in pigeons and 4.0 in ducks. Physical signs included tremors, polydipsia (pigeons) and wing carriage abnormalities. Pathologic tissue lesions were rare. High performance liquid chromatography (HPLC) of tissues indicated rapid urinary excretion of DA. DA was detected in pigeon urates at 15 minutes post injection peaked at 150 minutes and rapidly dropped to detection limits. The elimination half-life in pigeons was 132 minutes. Kidney had higher DA concentrations than serum or liver.; The pathologic effects of intracoelomically injected DA in 15 common murres (Uria aalge) was examined. The LD₅₀ was 4.1. Physical signs included hypothermia, abducted wing carriage and decreased mobility. Pathologic tissue lesions were rare. HPLC of tissues indicated rapid urinary excretion. Highest levels of DA were detected 1.5–3.0 hours post injection in urates.; The temporal progression of DA induced lesions in rats was examined with hematoxylin and eosin (HE) and Fluoro-Jade (FJ) staining. Post-dose survival groups (n = 4/group) were 2, 4, 8, 24, and 72 hrs. At 2–4 hrs post injection, lesions consisted of neuronal hyperchromasia and mild FJ positivity in the hippocampus. At 8–72 hrs, limbic system injury was present, evident with HE and strong FJ positivity. FJ enabled identification of injured areas at low magnifications.; Histology is a useful adjunct technique to diagnose DA toxicity in marine mammals but unrewarding in seabirds. Rapid collection and HPLC analysis of urates and gastrointestinal content is recommended for diagnosis in seabirds.