In Vivo Evaluation of the Chronic Oral Toxicity of the Marine Toxin Palytoxin

Abstract

Palytoxin (PLTX) is one of the most poisonous substances known to date and considered as an emergent toxin in Europe. Palytoxin binds to the Na+-K+ ATPase, converting the enzyme in a permeant cation channel. This toxin is known for causing human fatal intoxications associated with the consumption of contaminated fish and crustaceans such as crabs, groupers, mackerel, and parrotfish. Human intoxications by PLTX after consumption of contaminated fishery products are a serious health issue and can be fatal. Different reports have previously explored the acute oral toxicity of PLTX in mice. Although the presence of palytoxin in marine products is currently not regulated in Europe, the European Food Safety Authority expressed its opinion on PLTX and demanded assessment for chronic toxicity studies of this potent marine toxin. In this study, the chronic toxicity of palytoxin was evaluated after oral administration to mice by gavage during a 28-day period. After chronic exposure of mice to the toxin, a lethal dose 50 (LD50) of 0.44 µg/kg of PLTX and a No-Observed-Adverse-Effect Level (NOAEL) of 0.03 µg/kg for repeated daily oral administration of PLTX were determined. These results indicate a much higher chronic toxicity of PLTX and a lower NOAEL than that previously described in shorter treatment periods, pointing out the need to further reevaluate the levels of this compound in marine products.

Marine natural products

“…A daily 28 day exposure of mice to palytoxin induced changes to blood chemistry and established a chronic oral toxicity of LD 50 0.44 μg kg −1 and a no-observed-adverse-effect-level of 0.03 μg kg −1 , suggesting regulatory levels of the toxin should be re-evaluated. 613 Re-isolation of the lipid prostaglandin A 2 from Plexaura homomalla prompted evaluation of it, and three semisynthetic analogues, for antitumour related properties, identifying the NP as a weak inhibitor of p38α-kinase, Src-kinase and topoisomerase IIα. 614 The tetraprenylated lipid alkaloids belonging to the malonganenone/nuttingin family are known to exhibit cytotoxicity and antiplasmodial activities.…”

Current Trends and New Challenges in Marine Phycotoxins

“…This assay considers the death of the mice after intraperitoneal administration of the compounds, though the main consequence of most of these intoxications is not death but the reported acute symptoms after oral or epidermal exposure mentioned above [ 39 , 40 , 41 ] and long-term sequelae for some toxins, as is the case for CTXs [ 42 ]. There is scarce information about the impacts of long-term low-level exposure [ 41 , 43 , 44 , 45 ]. These types of studies are necessary to re-evaluate the real risk of the exposure of humans to these toxins since the main health risk for humans is a chronic exposure to low levels of these toxins.…”

Emerging Marine Biotoxins in European Waters: Potential Risks and Analytical Challenges

“…Recently, the chronic toxicity of PLTX was evaluated after oral administration to mice by gavage during a 28-day. A lethal dose 50 (LD50) of 0.44 µg/kg of PLTX and a NOAEL of 0.03 µg/kg for repeated daily oral administration of PLTX were fixed [ 106 ].…”