Acute Toxicity by Oral Co-Exposure to Palytoxin and Okadaic Acid in Mice

Abstract

The frequent occurrence of marine dinoflagellates producing palytoxin (PLTX) or okadaic acid (OA) raises concern for the possible co-presence of these toxins in seafood, leading to additive or synergistic adverse effects in consumers. Thus, the acute oral toxicity of PLTX and OA association was evaluated in mice: groups of eight female CD-1 mice were administered by gavage with combined doses of PLTX (30, 90 or 270 μg/kg) and OA (370 μg/kg), or with each individual toxin, recording signs up to 24 h (five mice) and 14 days (three mice). Lethal effects occurred only after PLTX (90 or 270 μg/kg) exposure, alone or combined with OA, also during the 14-day recovery. PLTX induced scratching, piloerection, abdominal swelling, muscle spasms, paralysis and dyspnea, which increased in frequency or duration when co-administered with OA. The latter induced only diarrhea. At 24 h, PLTX (90 or 270 μg/kg) and OA caused wall redness in the small intestine or pale fluid accumulation in its lumen, respectively. These effects co-occurred in mice co-exposed to PLTX (90 or 270 μg/kg) and OA, and were associated with slight ulcers and inflammation at forestomach. PLTX (270 μg/kg alone or 90 μg/kg associated with OA) also decreased the liver/body weight ratio, reducing hepatocyte glycogen (270 μg/kg, alone or combined with OA). No alterations were recorded in surviving mice after 14 days. Overall, the study suggests additive effects of PLTX and OA that should be considered for their risk assessment as seafood contaminants.

Okadaic Acid Is at Least as Toxic as Dinophysistoxin-1 after Repeated Administration to Mice by Gavage

“…In another study, oral administration of low dose OA for 7 days did not alter serum AST and ALT levels or liver histology [40]. It was reported more recently that a single exposure to 370 µg/kg of OA slightly increased serum AST and ALT levels but did not induce alterations in the liver [41]. In other studies, OA concentrations in the liver were low, and no pathological changes were observed [23,42].…”

Acute Toxicity of the Dinoflagellate Amphidinium carterae on Early Life Stages of Zebrafish (Danio rerio)

“…Dinoflagellates are generally notorious for their propensity to produce benthic harmful algal blooms (BHABs) containing marine biotoxins [2], which have a global impact on public health and aquatic ecological sustainability [3][4][5], thereby attracting the attention of the SCOR-IOC Global Ecology and Oceanography on Harmful Algal Blooms (GEO-HAB) program [6]. Lipophilic polyether phycotoxins from benthic dinoflagellates, such as palytoxin [7], ciguatoxins [8], and okadaic acid [9], may act as allelochemicals to help dinoflagellates gain a competitive advantage over benthic organisms [10,11], posing serious threats to human health when accumulated in seafood through the marine food chain [12,13].…”