Abstract
The marine polyether palytoxin (PLTX) is one of the most toxic natural compounds, and is involved in human poisonings after oral, inhalation, skin and/or ocular exposure. Epidemiological and molecular evidence suggest different inter-individual sensitivities to its toxic effects, possibly related to genetic-dependent differences in the expression of Na+/K+-ATPase, its molecular target. To identify Na+/K+-ATPase subunits, isoforms correlated with in vitro PLTX cytotoxic potency, sensitivity parameters (EC50: PLTX concentration reducing cell viability by 50%; Emax: maximum effect induced by the highest toxin concentration; 10−7 M) were assessed in 60 healthy donors’ monocytes by the MTT (methylthiazolyl tetrazolium) assay. Sensitivity parameters, not correlated with donors’ demographic variables (gender, age and blood group), demonstrated a high inter-individual variability (median EC50 = 2.7 × 10−10 M, interquartile range: 0.4–13.2 × 10−10 M; median Emax = 92.0%, interquartile range: 87.5–94.4%). Spearman’s analysis showed significant positive correlations between the β2-encoding ATP1B2 gene expression and Emax values (rho = 0.30; p = 0.025) and between Emax and the ATP1B2/ATP1B3 expression ratio (rho = 0.38; p = 0.004), as well as a significant negative correlation between Emax and the ATP1B1/ATP1B2 expression ratio (rho = −0.30; p = 0.026). This toxicogenetic study represents the first approach to define genetic risk factors that may influence the onset of adverse effects in human PLTX poisonings, suggesting that individuals with high gene expression pattern of the Na+/K+-ATPase β2 subunit (alone or as β2/β1 and/or β2/β3 ratio) could be highly sensitive to PLTX toxic effects.
Highlights
Palytoxin (PLTX) is one of the most potent marine toxins, originally identified in Palythoa zoanthids corals [1]
The main problem in tropical areas is represented by PLTX accumulation in edible marine organisms, the consumption of which has been associated with a series of severe human poisonings, sometimes with fatal outcomes
In a poisoning episode occurred in The Netherlands, 4 patients were exposed at the same time to vapours coming from the same home aquarium containing PLTX-contaminated soft corals but only two of them developed several symptoms persisting for few months [24]
Summary
Palytoxin (PLTX) is one of the most potent marine toxins, originally identified in Palythoa zoanthids corals [1]. Differences in inter-individual sensitivities can be noticed considering the documented cases of poisonings associated with inhalational exposure to vapors generated during the cleaning procedures of aquaria containing soft corals contaminated by PLTXs. In particular, in a poisoning episode occurred in The Netherlands, 4 patients were exposed at the same time to vapours coming from the same home aquarium containing PLTX-contaminated soft corals but only two of them developed several symptoms (i.e., dyspnoea and fatigue) persisting for few months [24]. In a poisoning episode occurred in The Netherlands, 4 patients were exposed at the same time to vapours coming from the same home aquarium containing PLTX-contaminated soft corals but only two of them developed several symptoms (i.e., dyspnoea and fatigue) persisting for few months [24] Even though these different inter-individual toxic responses may be due to several factors, such as concomitant pathologies or different exposure levels, a genetic-based variable individual sensitivity to PLTX could be hypothesized. The results would provide a contribution to identify genetic risk factors for the toxic outcomes
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