Toxicity and pathophysiology of palytoxin congeners after intraperitoneal and aerosol administration in rats

Abstract

Preparations of palytoxin (PLTX, derived from Japanese Palythoa tuberculosa) and the congeners 42-OH-PLTX (from Hawaiian P. toxica) and ovatoxin-a (isolated from a Japanese strain of Ostreopsis ovata), as well as a 50:50 mixture of PLTX and 42-OH-PLTX derived from Hawaiian P. tuberculosa were characterized as to their concentration, composition, in-vitro potency and interaction with an anti-PLTX monoclonal antibody (mAb), after which they were evaluated for lethality and tissue histopathology after intraperitoneal (IP) and aerosol administration to rats. Once each preparation was characterized as to its toxin composition by LC-HRMS and normalized to a total PLTX/OVTX concentration using HPLC-UV, all four preparations showed similar potency towards mouse erythrocytes in the erythrocyte hemolysis assay and interactions with the anti-PLTX mAb. The IP LD values derived from these experiments (0.92, 1.93, 1.81 and 3.26 μg/kg, for the 50:50 mix, 42-OH-PLTX, PLTX, and ovatoxin-a, respectively) were consistent with published values, although some differences from the published literature were seen. The aerosol LD values (0.063, 0.045, 0.041, and 0.031 μg/kg for the 50:50 mix, 42-OH PLTX, PLTX, and ovatoxin-a, respectively) confirmed the exquisite potency of PLTX suggested by the literature. The tissue histopathology of the different toxin preparations by IP and aerosol administration were similar, albeit with some differences. Most commonly affected tissues were the lungs, liver, heart, salivary glands, and adrenal glands. Despite some differences, these results suggest commonalities in potency and mechanism of action among these PLTX congeners.

Chemical Ecology of the Benthic Dinoflagellate Genus Ostreopsis: Review of Progress and Future Directions

“…Poli et al (2018) have reported differences of toxicity between PLTX and some of its analogs (42-OH-PLTX and OVTXa) by exposing rats to these toxins trough intraperitoneal routes and aerosol exposures and confirmed results already published by others colleagues (Tubaro et al, 2011;Ciminiello et al, 2013). noted huge differences of toxicity between OVTX a and PLTX: OVTX-a is 10 to 100 times less potent than the other but data obtained by Poli et al (2018) showed only minimal differences. Such differences could explain the difficulties to compare toxin analogs concentrations from NW Mediterranean and Adriatic strains.…”

“…More recently, high purity PLTX administration in mice showed that toxicity is dependent upon the route of administration (Munday, 2011). Poli et al (2018) characterized the toxicity and basic histopathological effects of PLTX (derived from Japanese Palythoa tuberculosa), the analog 42-OH-PLTX (from Hawaiian P. toxica) and ovatoxin-a (isolated from a Japanese strain of Ostreopsis ovata) after intraperitoneal and aerosol administration to rats. All toxin preparations showed similar potency towards mouse erythrocytes in the erythrocyte hemolysis assay and interactions with the anti-PLTX mAb (antibody).…”

Toxin content of Ostreopsis cf. ovata depends on bloom phases, depth and macroalgal substrate in the NW Mediterranean Sea

“…Toxicity may result from the production of palytoxin-like molecules, a family of highly potent marine toxins (Poli et al, 2018) including isobaric palytoxin (isob-PLTX) and more than a dozen ovatoxins (OVTX-a to -l) (Ciminiello et al, 2008;Ciminiello et al, 2010;Ciminiello et al, 2012a;Ciminiello et al, 2012b;Brissard et al, 2015;García-Altares et al, 2015;Tartaglione et al, 2016;Tartaglione et al, 2017). OVTXs are produced by both O. cf.…”

A Novel Sensitive Cell-Based Immunoenzymatic Assay for Palytoxin Quantitation in Mussels

“…Only a few of these analogues have been studied from a biological and chemical point of view, including (i) 42-hydroxy-PLTX (42 S -OH-50 S -PLTX), isolated from P. toxica [ 2 , 17 ], and its stereoisomer (42 S -OH-50 R -PLTX), isolated from P. tuberculosa [ 3 ]; (ii) ostreocin-D (OST-D) and its analogues, produced by Ostreopsis siamensis [ 11 , 18 , 19 , 20 ]; and (iii) ovatoxin-a (OVTX-a), the most abundant PLTX analogue, produced by Ostreopsis cf. ovata in the Mediterranean Sea [ 21 , 22 , 23 ].…”