Departamento de Farmacología, Facultad de Veterinaria, Universidade de Santiago de Compostela, 27002, Lugo, Spain.
Fisheries Technology Institute, National Research and Development Agency, Japan Fisheries Research and Education Agency, Yokohama, 236-8648, Japan.
Arch Toxicol. 2021 Aug;95(8):2797-2813. doi: 10.1007/s00204-021-03095-z. Epub 2021 Jun 20.
The consumption of contaminated shellfish with okadaic acid (OA) group of toxins leads to diarrhoeic shellfish poisoning (DSP) characterized by a set of symptoms including nausea, vomiting and diarrhoea. These phycotoxins are Ser/Thr phosphatase inhibitors, which produce hyperphosphorylation in cellular proteins. However, this inhibition does not fully explain the symptomatology reported and other targets could be relevant to the toxicity. Previous studies have indicated a feasible involvement of the nervous system. We performed a set of in vivo approaches to elucidate whether neuropeptide Y (NPY), Peptide YY (PYY) or serotonin (5-HT) was implicated in the early OA-induced diarrhoea. Fasted Swiss female mice were administered NPY, PYY(3-36) or cyproheptadine intraperitoneal prior to oral OA treatment (250 µg/kg). A non-significant delay in diarrhoea onset was observed for NPY (107 µg/kg) and PYY(3-36) (1 mg/kg) pre-treatment. On the contrary, the serotonin antagonist cyproheptadine was able to block (10 mg/kg) or delay (0.1 and 1 mg/kg) diarrhoea onset suggesting a role of 5-HT. This is the first report of the possible involvement of serotonin in OA-induced poisoning.
食用受 okadaic 酸(OA)组毒素污染的贝类会导致腹泻性贝类中毒(DSP),其特征是一组包括恶心、呕吐和腹泻在内的症状。这些藻毒素是 Ser/Thr 磷酸酶抑制剂,会导致细胞蛋白过度磷酸化。然而,这种抑制作用并不能完全解释报告的症状,其他靶标可能与毒性有关。先前的研究表明,神经系统可能会受到影响。我们进行了一系列体内研究,以阐明神经肽 Y(NPY)、肽 YY(PYY)或 5-羟色胺(5-HT)是否与 OA 诱导的早期腹泻有关。禁食的瑞士雌性小鼠在口服 OA 治疗(250μg/kg)前腹腔内给予 NPY、PYY(3-36)或赛庚啶。NPY(107μg/kg)和 PYY(3-36)(1mg/kg)预处理可使腹泻发作时间出现非显著性延迟。相反,5-HT 拮抗剂赛庚啶能够阻断(10mg/kg)或延迟(0.1 和 1mg/kg)腹泻发作,表明 5-HT 可能发挥作用。这是首次报道 5-HT 可能参与 OA 诱导的中毒。