Current Trends and New Challenges in Marine Phycotoxins

Abstract

Marine phycotoxins are a multiplicity of bioactive compounds which are produced by microalgae and bioaccumulate in the marine food web. Phycotoxins affect the ecosystem, pose a threat to human health, and have important economic effects on aquaculture and tourism worldwide. However, human health and food safety have been the primary concerns when considering the impacts of phycotoxins. Phycotoxins toxicity information, often used to set regulatory limits for these toxins in shellfish, lacks traceability of toxicity values highlighting the need for predefined toxicological criteria. Toxicity data together with adequate detection methods for monitoring procedures are crucial to protect human health. However, despite technological advances, there are still methodological uncertainties and high demand for universal phycotoxin detectors. This review focuses on these topics, including uncertainties of climate change, providing an overview of the current information as well as future perspectives.

Keywords: detection methods; mechanism of action; phycotoxin; therapeutic application; toxicity.

Figure 9

New challenges associated with marine phycotoxins outlined in this review.

Figure 1

Chemical structure of the representative compounds of each group of toxins mentioned in the text: saxitoxin (A), tetrodotoxin (B), domoic acid (C), okadaic acid (D), pectenotoxin 2 (E), azaspiracid 1 (F), yessotoxin (G), Pacific ciguatoxin 1 (H), palytoxin (I), brevetoxin 1 (J), and brevetoxin 2 (K).

Figure 2

Mechanisms of action of marine biotoxins. Saxitoxin (STX) and tetrodotoxin (TTX) bind to voltage gated sodium channels (VGSCs) site 1, blocking Na⁺ flux. Consequently, action potential transmission is suppressed in neurons and muscles, resulting in paralytic shellfish poisoning (PSP) and TTX poisoning, respectively. Ciguatoxins (CTXs) and Brevetoxins (BTXs) bind to VGSCs site 5, keeping the channel in an open state. Increased Na⁺ influx triggers action potential in excitable cells, leading to Ciguatera and Neurotoxic Shellfish Poisoning (NSP), respectively. Palytoxins (PLTXs) block the active transport of Na⁺ and K⁺ by Na⁺/K⁺ ATPase, converting the pump in a non-selective cation channel. The ion imbalance results in the wide symptomatology of PLTX poisoning. Okadaic acid (OA) is known to inhibit Ser/Thr protein phosphatases, resulting in proteins’ hyperphosphorylation. However, its relationship with the symptomatology developed and, thus, diarrhetic shellfish poisoning (DSP) is unclear. Domoic acid (DA) bind to kainate and AMPA receptors in neurons inducing cells overexcitability. As a result, amnesic shellfish poisoning (ASP) is developed. Cyclic imines (CIs) are competitive antagonists of nicotinic acetylcholine receptors (nAChRs). Therefore, they reversely block ACh stimulated muscle contraction. The azaspiracids (AZAs) molecular pathway leading to AZAs shellfish poisoning (AZP) remains unknown.

Figure 3

Chemical structure of the main saxitoxin analogues.

Figure 4

Chemical structure of ciguatoxin analogues.

Figure 5

Criteria in which toxicity equivalency factors (TEFs) are established are ranked based on their importance. Firstly, epidemiological data and clinical course reported from poisoning outbreaks along with the identified responsible toxin. Data obtained from in vivo assessments are then considered. Approaches such as the route of toxin administration or toxin quality are taken into account to evaluate relative potencies. Moreover, the toxicological measurement allowing for comparison between analogues should be selected based on symptoms observed in humans. This is, when the toxin causes death, a median lethal dose is recommended; however, the main symptom should be evaluated if no reported cases of fatalities are known. Finally, in vitro experimental reports allow to study the molecular target. The biological system should be corresponding to the observed affected/targeted tissues or organs in vivo. Even though the preferential order has been described, our proposal is to consider in vitro and in vivo information complementary for the establishment of TEFs. In vitro assays can also provide essential data that help in understanding the mechanism of action. This implies the relative potency of analogues or the clinical course expected to be observed in vivo. Similarly, in vivo studies are fundamental in determining TEFs even when human poisoning data are available. Modified from FAO/WHO (2016) [70].

Figure 6

Chemical structure of the main okadaic acid analogues.

Figure 7

Chemical structure of azaspiracid analogues.

Figure 8

Chemical structure of the main cyclic imines: pinnatoxin A (A), spirolide A (B), portimine (C), gymnodimine A (D), pteriatoxin A (E), prorocentrolide (F), and spiro-prorocentrimine (G).