Toxicological effects and mechanisms of selected foodborne toxins in medaka and zebrafish models

Abstract

Foodborne toxins include a variety of biologically produced toxins and process-induced toxicants. Among them, marine algal toxins in polluted seafood can induce serious harmful effects on human, while heat-induced toxicants remain in a wide range of food and chronically affect health. In this present study, several representative toxins from these two categories were selected and studied, they are, brevetoxins (PbTxs), saxitoxin (STX) and acrolein (ACR). During past decades, the molecular actions of these toxins have been well studied, however, their effects and mechanisms corresponding to their sublethal toxicity in vivo still need more investigation. Therefore, in our current study, we adopted medaka fish (Oryzias melastigma) and zebrafish (Danio rerio) as models to study the toxicological responses and pathways of these selected toxins at the molecular and cellular level.

In the first part of study, the targeted organs of medaka fish, gills and brains, were studied in medaka fish after exposure to the sublethal level of PbTx-1, the most potent neurotic shellfish poisoning (NSP) toxin. Facilitated by the two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ ionization tandem time-of-flight mass spectrometry (MALDI TOF/TOF MS), proteins affected by PbTx-1 in these organs were identified, including myosin like proteins, aldose reductase, gelsolin and keratin. Collectively, the proteins altered after exposure suggested the altered calcium ion binding process, and dysfunction in cytoskeleton assembly and metabolism.

After successfully applying the fish model and proteomic approaches in the NSP toxin study, we put emphasis on the developmental toxicity of foodborne toxins, as children are more sensitive and vulnerable to foodborne toxins. Among the marine algal toxins, paralytic shellfish poisoning (PSP) toxins are the commonest and most lethal ones with STX as the most potent PSP toxin. Therefore, we examined the developmental effects of STX using medaka model. By exposing medaka embryos from the early blastula stage onwards, which covered the main developmental stage of the central nervous system and somites, we found newly hatched medaka fish exhibit abnormal growth with longer body length and relatively smaller yolk sac size. High cell proliferation, neuron development, and metabolism were confirmed by whole-mount immunostaining and 2-DE. In summary, STX disturbs the normal growth of medaka embryos probably by affecting the metabolic rate in the exposed medaka embryos.

Opposite to STX, after exposure to ACR, a pollutant that ubiquitously exists in food and environment, the zebrafish exhibited delayed development. ACR is a known glutathione (GSH) depleting factor and oxidative stress inducer. Apart from developmental retardance, increased reactive oxygen species (ROS) and inflammation were found in newly hatched zebrafish, suggesting the developmental delay may be partly related to the ACR-induced oxidative stress.

In summary, findings from the present study highlighted the molecular responses and possible pathways of some selected foodborne toxins. Developmental effects and toxicity were also found after exposing to both the biologically produced toxin and the heat-produced toxicant. Our current study makes contributions to the knowledge on the hazardous effects of foodborne toxins in vivo, and provides useful information for the further study on the human health.