RT Journal Article T1 Intestinal secretory mechanisms in Okadaic acid induced diarrhoea A1 Costas Sánchez, Celia A1 Louzao Ojeda, María del Carmen A1 Raposo García, Sandra A1 Vale González, María del Carmen A1 Rodríguez Vieytes, Mercedes A1 Botana López, Luis Miguel K1 Okadaic acid K1 Diarrhoea K1 Serotonin K1 Stools electrolytes K1 Tight junctions AB Okadaic acid (OA) is an important marine lipophilic phycotoxin responsible for diarrhetic shellfish poisoning (DSP). This toxin inhibits protein phosphatases (PPs) like PP2A and PP1, though, this action does not explain OA-induced toxicity and symptoms. Intestinal epithelia comprise the defence barrier against external agents where transport of fluid and electrolytes from and to the lumen is a tightly regulated process. In some intoxications this balance becomes dysregulated appearing diarrhoea. Therefore, we evaluated diarrhoea in orally OA-treated mice as well as in mice pre-treated with several doses of cyproheptadine (CPH) and then treated with OA at different times. We assessed stools electrolytes and ultrastructural alteration of the intestine, particularly evaluating tight and adherens junctions. We detected increased chloride and sodium faecal concentrations in the OA-exposed group, suggesting a secretory diarrhoea. Pre-treatment with CPH maintains chloride concentration in values similar to control mice. Intestinal cytomorphological alterations were observed for OA mice, whereas CPH pre-treatment attenuated OA-induced damage in proximal colon and jejunum at 2 h. Conversely, tight junctions’ distance was only affected by OA in jejunum at the moment diarrhoea occurred. In this study we found cellular mechanisms by which OA induced diarrhoea revealing the complex toxicity of this compound PB Elsevier YR 2022 FD 2022 LK http://hdl.handle.net/10347/29387 UL http://hdl.handle.net/10347/29387 LA eng NO Food and Chemical Toxicology 169 (2022) 113449 NO The research leading to these results has received funding from the following FEDER cofunded-grants. From Conselleria de Cultura, Educacion e Ordenación Universitaria, Xunta de Galicia, GRC (ED431C 2021/01). From Ministerio de Ciencia e Innovación IISCIII/PI19/001248, PID 2020-11262RB-C21. From European Union Interreg Agritox EAPA-998-2018, and H2020 778069-EMERTOX. Authors would like to thank the use of RIAIDT-USC analytical and microscopic facilities. Celia Costas is recipient of a fellowship from the Ministerio de Ciencia, Innovacion y Universidades (FPU18/05681 DS Minerva RD 23 abr 2026