期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 169, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2022.113449
关键词
Okadaic acid; Diarrhoea; Serotonin; Stools electrolytes; Tight junctions
资金
- FEDER
- Ministerio de Ciencia, Innovacion y Universidades [FPU18/05681]
- Conselleria de Cultura, Educacion e Ordenacion Universitaria, Xunta de Galicia, GRC [ED431C 2021/01]
- Ministerio de Ciencia e Innovacion [IISCIII/PI19/001248, PID 2020-11262RB-C21]
- European Union [EAPA-998-2018, 778069-EMERTOX]
In this study, the researchers evaluated the effect of Okadaic acid (OA) on diarrhea using mice models. The results showed that OA exposure led to an increase in chloride and sodium concentration in the feces, indicating a secretory diarrhea. However, pre-treatment with cyproheptadine (CPH) attenuated the damage caused by OA in the colon and jejunum. The study identified cellular mechanisms underlying OA-induced diarrhea and highlighted the complex toxicity of this compound.
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.
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