Investigations into the Toxicology of Spirolides, a Group of Marine Phycotoxins

Abstract

Spirolides are marine phycotoxins produced by the dinoflagellates Alexandrium ostenfeldii and A. peruvianum. Here we report that 13-desmethyl spirolide C shows little cytotoxicity when incubated with various cultured mammalian cell lines. When administered to mice by intraperitoneal (ip) injection, however, this substance was highly toxic, with an LD50 value of 6.9 µg/kg body weight (BW), showing that such in vitro cytotoxicity tests are not appropriate for predicting the in vivo toxicity of this toxin. Four other spirolides, A, B, C, and 20-methyl spirolide G, were also toxic to mice by ip injection, with LD50 values of 37, 99, 8.0 and 8.0 µg/kg BW respectively. However, the acute toxicities of these compounds were lower by at least an order of magnitude when administration by gavage and their toxic effects were further diminished when administered with food. These results have implications for future studies of the toxicology of these marine toxins and the risk assessment of human exposure.

Characterization of multiple isolates from an Alexandrium ostenfeldii bloom in The Netherlands

“…SPX and gymnodimines are fast acting highly toxic neurotoxins, with LD 50 values (i.p. mice) down to 6.9 and 96 mg kg À1 body weight, respectively (Munday et al, 2004(Munday et al, , 2012. Besides toxicity, various Alexandrium species were shown to have allelopathic potencies toward grazers and other phytoplankton species (Tillmann and John, 2002;Tillmann et al, 2007Tillmann et al, , 2008John et al, 2015).…”

Regulation of spiroimine neurotoxins and hemolytic activity in laboratory cultures of the dinoflagellate Alexandrium peruvianum (Balech & Mendiola) Balech & Tangen

“…A recent study also demonstrated that specific bioactive spirolides vector untransformed through shellfish via a mechanism of hydrolysis resistance (Christian et al, 2008). Mysteriously, two decades after spirolides were discovered it is still not known whether they present a risk to human health (Munday et al, 2012). As previously mentioned, similar uncertainties exist for gymnodimines.…”

Collaborative study for the detection of toxic compounds in shellfish extracts using cell-based assays. Part II: application to shellfish extracts spiked with lipophilic marine toxins

“…The first step in the study was to propose a screening strategy for characterizing and validating the responses of three cell lines representative of the main target organs of phycotoxins (intestinal Caco2, hepatic HepG2, and neuronal Neuro2a) when exposed to three lipophilic toxins (azaspiracid-1 (AZA1), okadaic acid (OA), and pectenotoxin-2 (PTX2)). Cyclic imines (such as spirolides) were not included in the study because of their low cytotoxic effect on different cell lines [22]. In part I, we demonstrated that the sensitivity and variability (repeatability and reproducibility) of the CBA responses with known lipophilic toxins on the three selected cell lines were similar within and between five participating laboratories.…”