NEUROPEPTIDE Y PROTECTIVE ROLE ON OKADAIC ACID INDUCED DIARRHOEA

Marine biotoxins portrait a major threat to public health. Microalgae, such as diatoms or dinoflagellates, are the major producers of these compounds. Blooms of these species commonly correspond with increased toxin concentration in filter-feeding organisms, which can lead to poisoning outbreaks due to shellfish consumption. Within toxins of marine origin, we focus our work on the okadaic acid (OA) group that also includes the analogues dynophysistoxins 1 and 2. Diarrheic Shellfish Poisoning (DSP) is developed after ingestion of contaminated food with these lipophilic compounds, consisting mainly on gastrointestinal symptoms like nausea and diarrhoea. OA group of toxins inhibit protein phosphatases (PPs) with ubiquitous distribution like PP1 or PP2A. Yet, several reports raise the possibility of the phycotoxin targeting different mechanisms. A substantial variety of pathogenic stimuli trigger diarrhoea through the activation of the Enteric Nervous System (ENS). Neuropeptide Y (NPY) is a 36 aa peptide of neuronal origin known to maintain an antisecretory tone by acting on the receptors Y₁ and Y₂, both expressed along the gastrointestinal tract. Previous in vitro studies have exposed that OA downregulates NPY gene and protein expression. Moreover, the toxin is reported to cause diarrhoea within the first 2 h of treatment. Here we assess how the pro-absorptive NPY could be modifying OA-induced diarrhoea in vivo. Mice were first given NPY via intraperitoneal 15 minutes prior to OA oral gavage administration. Body weight variations, symptoms along with food and water intake were monitored for the 2 h treatment. Afterwards, anatomopathological examination took place and intestine samples were collected for transmission electron microscopy evaluation. In the presence of NPY, no delay on diarrhoea onset was observed though ultrastructural mild recovery was detected in the large intestine. Hence, it could be feasible that OA modifies NPY antisecretory tone, resulting in diarrhoea.