title: Uptake, tissue distribution and excretion of domoic acid after oral exposure in coho salmon (Oncorhynchus kisutch).
abstract: Domoic acid (DA) is a potent neurotoxin naturally produced by some pennate diatom species of the genus Pseudo-nitzschia. It is well known that during harmful algal blooms fish can accumulate DA in the gastrointestinal (GI) tract and act as vectors of the toxin to higher trophic level piscivores, often with severe neurotoxic consequences to the predators. Although neurotoxicity and mass mortality have been observed in vertebrates (i.e. marine mammals and sea birds) feeding on contaminated fish, to date there has been no evidence of neurobehavioral toxicity in the fish vectors themselves. It has been hypothesized that fish may not absorb DA from the digestive tract, thus making them insensitive to dietary consumption of DA. To test this hypothesis, we performed oral gavage exposures followed by a time series of tissue dissections to characterize uptake, depuration, and tissue distribution of DA in fish. Intracoelomic (IC) injection exposures (which bypass the GI tract) were also performed to determine if coho neurons are neurologically susceptible to DA. Excitotoxic symptoms were observed in fish via IC injection at similar toxin levels that have been reported to induce excitotoxic symptoms in intraperitoneal (IP) exposures with mammalian models such as mice, suggesting that fish neurons have a similar sensitivity to DA as other vertebrates. Surprisingly, after oral gavage with ecologically relevant doses of DA, the toxin was detected in plasma collected from the dorsal aorta via a permanent intraarterial catheter within 15 min, yet excitotoxic symptoms were not observed. Additionally, DA was detected in liver, heart, spleen, kidney, muscle, brain and bile. These data indicate that although DA is absorbed from the gut, fish do not exhibit neuroexcitatory effects at maximum ecologically relevant oral doses of DA. Tissue distribution and DA uptake and depuration patterns suggest that a majority of the absorbed toxin is excreted via the kidneys and bile, thereby preventing toxic levels of DA from reaching sensitive nervous tissue. Additionally, greater than 20% of total IC administered DA doses were sequestered in bile within 1h of injection in five symptomatic fish, providing evidence for biliary sequestration of the toxin from blood. Here, we comprehensively describe the uptake, depuration, and tissue distribution patterns of DA and propose that renal and biliary processes may serve as primary routes of toxin clearance in fish.
authors.affiliation: NOAA Fisheries, Northwest Fisheries Science Center, Environmental Conservation Division, Marine Biotoxins Program, 2725 Montlake Blvd. East, Seattle, WA 98112, USA. Kathi.Lefebre@noaa.gov
authors.forename: Kathi A
authors.initials: KA
authors.lastname: Lefebvre
authors.forename: Dawn P
authors.initials: DP
authors.lastname: Noren
authors.forename: Irvin R
authors.initials: IR
authors.lastname: Schultz
authors.forename: Sara M
authors.initials: SM
authors.lastname: Bogard
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Wilson
authors.forename: Bich-Thuy L
authors.initials: BT
authors.lastname: Eberhart
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007267:Injections / Q000662:veterinary; D007408:Intestinal Absorption; D007608:Kainic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008387:Marine Toxins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D000432:Methanol / Q000737:chemistry; D023421:Models, Animal; D009498:Neurotoxins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D017684:Oncorhynchus kisutch / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D008387:Marine Toxins; D009498:Neurotoxins; C012301:domoic acid; D007608:Kainic Acid; D000432:Methanol