Titolo: The increasing risk of consumer exposure to DSP algal toxins: in vitro/in vivo approach with the pig as a new animal model

Bando: PRIN

Durata:  24 mesi

Coordinatore: PROF. MAURO DACASTO

Budget BCA: € 84.824,00

Responsabile scientifico: prof. Mauro Dacasto

Research Team: DACASTO MAURO

Abstract: Harmful algal blooms (HAB) are natural phenomena caused by the massive growth of phytoplankton that currently represent one of the most prevalent sources of marine pollution. They can produce high concentrations of potentially harmful algal biotoxins (ALTOX) that cause poisoning to both aquatic organisms and humans. ALTOX accumulate in the food chain (i.e., in the bivalve mollusks) and their increased occurrence, due to climate change and eutrophication, is a worldwide public health concern. Such phenomenon is heavily affecting the aquaculture sector with severe economic losses resulting from the closure of coastal areas, including production sites, and the marketing ban of contaminated mollusks exceeding the EU limits. In the Northern Adriatic Sea, an area highly exploited for mollusk farming, recurrent cases of ALTOX bioaccumulation have been reported, including increasing and persistent concentrations of okadaic acid (OA), one of the most important lipophilic ALTOX causing Diarrheic Shellfish Poisoning (DSP). The current knowledge about the mechanisms involved in OA toxicity, its local or systemic effects, as well as its toxicokinetics in mammals, needs to be extended. Thus, there is a great interest from fishermen and shellfish farmers for additional information about the effects of OA exposure in consumers to promote a revision of its risk assessment. The major aim of the proposal (acronym, MOKAPIG) is to obtain data about the OA concentrations that could be considered safe for the consumers, addressing the fishermen and shellfish farmers requests, and supporting the potential revision of the OA limits. Such goal will be achieved through both in vitro and in vivo studies in target organs (liver and gut) of human and swine origin. The selection of the pig species originates from its similarity to humans in terms of anatomy, physiology, and drug metabolism. First, comparative studies on OA cytotoxicity, uptake and metabolism will be performed in selected human and pig cell lines, by means of cell viability assays, intestinal barrier models and LC-MS/MS analyses. Then, to characterize the biomolecular pathways/networks activated by OA, a whole transcriptomics analysis, followed by confirmatory gene and protein expression studies, will be applied in the same cell lines. Finally, an in vivo study, using the pig as a possible alternative model to the mouse, will corroborate the comparative data obtained in the in vitro experiments, and will (hopefully) recapitulate more faithfully the human poisoning. The results of MOKAPIG are expected to significantly improve the knowledge about OA toxicity in mammals, addressing the requests of the stakeholders (e.g., fishermen, shellfish farmers, consumers). The potential practical application relies in the possibility to derive from our data update information about safe or toxic concentrations of OA useful to revise the current limits, with obvious economic and social benefits.