title: Toxicokinetics of the ciguatoxin P-CTX-1 in rats after intraperitoneal or oral administration.
abstract: Ciguatoxins are voltage-gated selective algal toxins responsible for ciguatera fish poisoning. In this study we evaluate the toxicokinetics of one of the most common ciguatoxins found in the Pacific, the P-CTX-1, in rat after an oral or intraperitoneal (ip) dose of 0.26 μg/kg body weight. We report levels of ciguatoxin activity assessed over time in blood, urine and feces, and at 4 days in liver, muscle and brain, using the functional in vitro N2A cytotoxicity assay. Following exposure, the ciguatoxin activity exhibited a rapid systemic absorption that was followed by a bi-exponential decline, and data best fit a two-compartment model analysis. Maximum blood concentrations were reached at 1.97 and 0.43 h after the oral and ip dose, respectively. Ciguatoxin elimination from blood was slow with terminal half lives (t(½)β) estimated at 82 h for oral and 112 h for ip dosing. Ciguatoxin activity remained in liver, muscle and brain 96 h after ip and oral administration. While smaller amounts appeared in the urine, the main excretion route was feces, with peak rates reaching > 10 pg P-CTX-1 equivalents/h in both routes of administration. Assay guided fractionation showed the presence in the feces and liver of peaks of activity corresponding to the P-CTX-1 and to other less polar metabolites. In conclusion, biologically active ciguatoxins are detectable in blood, liver, muscle and brain, and continued to be excreted in urine and feces 4 days following exposure. Blood, as well as urine and feces may be useful matrices for low-invasive testing methods for ciguatera clinical cases.
authors.affiliation: Marine Biotoxins Program, Center for Coastal Environmental Health and Biomolecular Research, NOAA-National Ocean Service, 219 Fort Johnson Road, Charleston, SC 29412, USA.
authors.forename: Marie-Yasmine Dechraoui
authors.initials: MY
authors.lastname: Bottein
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wang
authors.forename: John S
authors.initials: JS
authors.lastname: Ramsdell
mesh_terms: D000284:Administration, Oral; D000818:Animals; D036841:Ciguatera Poisoning / Q000139:chemically induced / Q000378:metabolism; D002922:Ciguatoxins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D004524:Eels; D007274:Injections, Intraperitoneal; D008297:Male; D010599:Pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
chemical_list: D002922:Ciguatoxins