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Blanco, J. Okadaic Acid Depuration from the Cockle Cerastoderma edule. Encyclopedia. Available online: https://encyclopedia.pub/entry/20832 (accessed on 13 July 2025).
Blanco J. Okadaic Acid Depuration from the Cockle Cerastoderma edule. Encyclopedia. Available at: https://encyclopedia.pub/entry/20832. Accessed July 13, 2025.
Blanco, Juan. "Okadaic Acid Depuration from the Cockle Cerastoderma edule" Encyclopedia, https://encyclopedia.pub/entry/20832 (accessed July 13, 2025).
Blanco, J. (2022, March 22). Okadaic Acid Depuration from the Cockle Cerastoderma edule. In Encyclopedia. https://encyclopedia.pub/entry/20832
Blanco, Juan. "Okadaic Acid Depuration from the Cockle Cerastoderma edule." Encyclopedia. Web. 22 March, 2022.
Okadaic Acid Depuration from the Cockle Cerastoderma edule
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The cockle Cerastoderma edule is a commercially important species in many European Countries. It can accumulate okadaic acid (OA) and other toxins in its group, which makes it unsuitable for human consumption, producing harvesting bans to avoid intoxications. The duration of those bans depends in part on the depuration kinetics of the toxin in this species. In this work, this kinetics was studied by means of fitting different models to depuration data experimentally obtained, using naturally contaminated cockles. Cockles depurated OA faster than most other bivalve species studied. Models that include Michaelis-Menten kinetics describe the depuration better than those using a first order exponential decrease to describe the first (or the only) compartment. One-compartment models were not able to describe the final part of the depuration curve, in which OA was depurated very slowly. Therefore, two-compartment models were needed. Esters were depurated at a much faster rate than the free form of the toxin; however, no significant esterification was detected during the process. The slow depuration rate suggests that other bivalve species could be used as sentinels to monitor cockle populations, but caution should be taken when toxin concentrations are very high. 

kinetics Michaelis-Menten models esterification

1. Introduction

Okadaic acid (OA) and dinophysistoxins (DTX) are compounds produced by several species of marine dinoflagellates and accumulated by other organisms, mainly bivalves. These toxins, when consumed by humans and other mammals, produce a syndrome known as diarrhetic shellfish poisoning (DSP). In benthic environments, several Prorocentrum species can produce these toxins [1][2][3][4]. In plankton, the main producers are species of Dinophysis, which can contain OA, DTX1, DTX2, some isomers, some derivatives, such as diol- and triol-esters [5][6][7][8][9], and occasionally the groups of compounds known as DTX4 and DTX5 (up to now not described in Dinophysis but found in some OA-producing benthic species) [10][11]. Dinophysis species are distributed worldwide and DSP intoxications by mollusk consumption have been reported from many countries [6]. After the discovery of DSP by Yasumoto et al. [12] and the development of an assay to quantify it, the detection of this toxicity was progressively incorporated into shellfish monitoring systems. Later, the development of analytical methods to quantify these toxins allowed for the creation of reference levels for their maximum content in bivalve soft tissues, which cannot be surpassed to consider the shellfish safe for consumption. Currently, in the European Union [13] and most other countries, this level has been established at 160 µg of OA-equivalents kg−1, a level which was established from an acute reference dose of 0.3 µg of OA kg−1 of body weight obtained from epidemiological data [14]. In many areas, the recorded toxin concentrations led to frequent bans of mollusk harvesting, which represent an important economic and social problem.
Mollusk, and especially bivalves, are appreciated as a source of food for humans and, consequently, their fisheries are commercially important. The cockle Cerastoderma edule, among the non-cultured mollusks, is one of the economically most important species in Europe. Its production between 2014 and 2017 ranged from 14,651 to 26,125 t, with the UK as the top producer and Spain the second [15]. In Galicia (NW Spain) the annual production is around 600 t [16], and represents an important resource for the people who gather shellfish from the intertidal zone (a regulated activity). Bans can produce significant economic losses in the productive sector, which are dependent on their duration.
Ban duration depends on the amount of toxins that the bivalves can ingest, which in turn depends on the abundance of toxic cells, the toxin contents of the cells, the time during which the toxic populations persist, and the depuration kinetics of the bivalve [17]. Banning periods could be substantially shortened for the species that depurates faster. For C. edule, OA depuration rate has only been roughly estimated but seems to be faster than that of the mussels M. galloprovincialis and M. edulis [18][19], and some clams and oysters (reviewed in [17]). Its depuration kinetics has not been studied, making it difficult to precisely predict the time course of its reduction of toxicity.

2. Current Insights

Cockles depurate most of their OA content faster than other studied bivalve species. They can reduce their toxin content by a half in 1.7 days. The rates observed in the mussels M. galloprovincialis and M. edulis are substantially lower than those found in this study, ranging from 0.05 to 0.19 day−1 [19][20][21][22][23][24][25][26] (reviewed in Blanco [17]). This is also the case with different infaunal bivalve species such as Spisula solida [27] and Donax trunculus [26][27]. Vale et al. [19] also found higher depuration rates of OA and DTX2 in cockles (0.22 day−1, recomputed from the fastest decay of the depuration curve) than in mussels (0.09 day−1).
The better fitting of the models, which include the Michaelis-Menten kinetics in relation to those using an exponential decay, suggests that a saturable transporter should be involved in the process. Consequently, when the amount of toxin accumulated is very high, the depuration is slower, in relation to the toxin concentration, than when the concentration is lower. This kind of response seems to also be present in the depuration data obtained by Vale et al. [19], but it is not frequent among bivalves, whose depuration usually follows an exponential decay [17]. The need of a second compartment, with very low depuration and transfer rates, in the models of total toxin indicates that there is a small amount of nearly residual toxin that could persist in cockles for a long time. The amount of this nearly residual toxin is very low and does not pose any risk for consumer health. The presence of a small second compartment for OA is frequent among bivalves [17].
Most toxin was found to be in esterified form. Esterification of xenobiotics with fatty acids seems to be a frequent step in depuration, and has been shown to take place with okadaic acid and analogs [28] and with steroids [29]. Most bivalves quickly esterify okadaic acid, making esters constitute more that 90% of the total toxin [17].
Esters are depurated from the cockle at a much higher rate than free toxin. This difference was also found in a previous study with the same species in Portugal [19], and was also the case in the mussels M. galloprovincialis [19] and M. edulis, but not in the oyster Ostrea edulis in Norway [30]. However, Lindegarth et al. [31], also from Norway, reported that free forms were depurated from mussels and oysters faster than the esters. Notwithstanding, an approximate re-computation from their plots using only the first two depuration weeks shows that the esterified forms depurate at a much higher rate (nearly 2x) than the free toxin in both species. The fact that the fit to the data did not improve when esterification of the free OA was included in the model suggests that this process had low importance during cockle depuration. This is surprising because it is known that free OA is easily esterified in bivalves [28][32][33] and, during four years of monitoring in Galicia, the percentage of free OA in cockle was nearly always below 5% of the total toxin [34], which would not be possible if the esterification was not very fast. One explanation for this is that most OA was already esterified at the beginning of the experiment (more than 98% of the OA), making it difficult to estimate the model parameters precisely. Another possible explanation would be that the esterification rate follows a sigmoid curve, with low esterification rates when the concentration of free OA is also low (due to inhibition by the product or other causes). Rossignoli et al. found that most OA was depurated from the mussel M. galloprovincialis in esterified form [35], even when the proportion of free form in that species is high, which suggests that free OA should be esterified before being excreted from the digestive gland cells. This would explain why the second compartment is relatively more important for free that for esterified OA.
The fast depuration rate observed suggests that cockles represent a smaller risk than other bivalves and, consequently, that other less valued species, such as mussels, can be used as sentinels to carry out an efficient monitoring system. However, some precaution should be taken when very high toxin concentrations are attained because, in those cases, with the observed kinetics, cockles can depurate the toxin slower than mussels and other species whose depuration follows a first-order exponential decay.
The identification of the membrane transporter most likely involved could allow for selecting fast depurating cockles or for the creation of design-specific treatments to accelerate depuration in the future.

References

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