Four toxins, okadaic acid (OA), dinophysistoxin-1 (DTX1), pectenotoxin-6 (PTX6), and yessotoxin (YTX), all associated with diarrhetic shellfish poisoning (DSP), were administered via syringe to Scallops Patinopecten yessoensis and their distribution in the hepatopancreas, adductor muscle, and combined other tissues (mantle, gill, gonad) was analyzed by liquid chromatography-mass spectrometry. Toxins exclusively remained in the hepatopancreas irrespective of the injection site, adductor muscle or hepatopancreas. When injected into hepatopancreas, OA, DTX1, and YTX were metabolized to 7-O-palmitoylOA, 7-O-palmitoylDTX1 and 45-hydroxyyessotoxin (45OH-YTX), respectively. Such metabolic changes were insignificant when toxins were injected into the adductor muscle. The residual ratio for each toxin in the hepatopancreas was less than 20%. Mortalities of scallops treated with PTX6 were lower than those treated with other toxins.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
毒性总结
潜在的有毒腹泻性贝类毒素(DSP)浮游生物甲藻... 包括浮游生物种类Dinophysis acuminata, D.caudata, D. fortii, D.hastata, D. mitra, D. rotundata, D. tripos以及底栖甲藻Prorocentrum lima, P. elegans, P. hoffmannianum和P.concavum... 这些物种无处不在,但它们的毒性是多变且不可预测的。浓密的藻华... 新西兰水域)有时可能完全没有毒性,但其他时候即使只有稀疏的甲藻种群存在,贝类也可能变得有毒。在新西兰,已经发生了两次小规模的DSP爆发。引起DSP毒素的是脂溶性聚醚化合物。第一种被化学特性表征的毒素是冈田酸(OA)... 随后的研究发现贝类中存在冈田酸衍生物,称为dino毒素(DTX),pectenotoxins(PTX,以扇贝属Pecten命名)和yessotoxins(YTX,以扇贝Patinopecten yessoensis命名)... 近年来,已经识别出大量新的DSP毒素,包括来自爱尔兰贻贝的DTX2和一种同分异构体,来自爱尔兰贻贝的新毒素KT3(现命名为螺旋酸),来自亚得里亚海D. fortii的pectenotoxin 2,来自Gonyaulax polyedra和Protoceratium reticulatum的yessotoxin和类似物。虽然yessotoxin具有很高的腹膜毒性,但其口服效力非常低,这种化合物可能需要被降级为DSP毒素... 腹泻效应仅对OA和DTX1和DTX3得到证实,而PTX1-4导致肝坏死,YTX在腹膜内注射到小鼠后损害心肌。一些腹泻毒素(OA和DTX1)是蛋白磷酸酶的强效抑制剂,这种作用方式可能与观察到的腹泻、小肠吸收上皮的退行性变化以及肿瘤促进有关。
Potentially toxic diarrhetic shellfish poisons (DSP) plankton dinoflagellates ... include the planktonic species Dinophysis acuminata, D.caudata, D. fortii, D.hastata , D. mitra, D. rotundata, D. tripos and the benthic dinoflagellates Prorocentrum lima, P. elegans, P. hoffmannianum and P.concavum ... . These species are omnipresent but their toxicity is variable and unpredictable. Dense blooms .... Zealand waters) can sometimes be completely non-toxic, but at other times shellfish can become toxic even when only sparse dinoflagellate populations are present. In New Zealand, there have been two small outbreaks of DSP. The causative DSP toxins are fat-soluble polyether compounds. The first toxin to be characterized chemically was okadaic acid (OA) ... Subsequent research revealed the presence in shellfish of okadaic acid derivatives, termed dinophysis toxins (DTX), pectenotoxins (PTX, after the scallop genus Pecten) and yessotoxins (YTX, after the scallop Patinopecten yessoensis) ... . In recent years, a large number of new DSP toxins have been recognised, including DTX2 and an isomer from Irish mussels, a new toxin KT3 (now named spiramino acid) from Irish mussels, pectenotoxin 2 from D. fortii in the Adriatic Sea, yessotoxin and analogues from Gonyaulax polyedra and Protoceratium reticulatum. While yessotoxin has a high intraperitoneal toxicity, its oral potency is very low, and this compound probably needs to be declassified as a DSP toxin ... .. Diarrhegenic effects have only been proven for OA and DTX1 and DTX3, whereas PTX1-4 causes liver necrosis and YTX damages cardiac muscle after intraperitoneal injection into mice. Some diarrhegenic toxins (OA and DTX1) are potent inhibitors of protein phosphatases and this mode of action may be linked to the observed diarrhea, degenerative changes in absorptive epithelium of the small intestine, and to tumor promotion.
/SIGNS AND SYMPTOMS/ In Antwerp, Belgium, 403 cases of diarrheic shellfish poisoning were reported after consumption of blue mussels. Symptoms included diarrhea, vomiting, abdominal pain, and nausea. The analysis of fecal specimens from patients allowed diagnosis exclusions for bacteria and viruses. Mouse-assays revealed the presence of biotoxins specific of dinoflagellates, which were identified and quantified by LC-MS. The mussels were imported from Denmark, and were part of a batch presenting high concentrations of okadaic acid above the regulatory limits. Diarrheic shellfish poisoning (DSP) is a foodborne illness caused by the consumption of shellfish which contain biotoxins elaborated by planktonic algae (marine dinoflagellates). It is a gastrointestinal disease with no neurological symptoms. The first reported cases were in the Netherlands in the 1960s. Since then, outbreaks have been described in Japan, Europe, South America, and the Far East. DSP is caused by a group of polyethers, including okadaic acid (OA), dinophysis toxins (DTXs), pectenotoxins (PTXs), and yessotoxin (YTXs) . Well documented cases in Belgium and Europe are rare, and this may partly be due to underdiagnosis and underreporting. This report describes an outbreak of diarrhetic shellfish poisoning after the consumption of blue mussels. The investigation was begun after a mandatory notification of several cases of presumptive food poisoning by general practitioners (GPs) to the Health Inspections department of infectious diseases (Gezondheidsinspectie).
/SIGNS AND SYMPTOMS/ The diarrhetic poisoning by bivalve molluscs, diarrhetic shellfish poisoning, is due to consumption of mussels containing biotoxins produced by some Dinoflagellate species. Toxic effects of yessotoxin (YTX) include morphological alterations of mitochondria from heart and liver ...
/ALTERNATIVE and IN VITRO TESTS/ The structure-activity relationship of yessotoxins (YTX) has been probed by measuring the potency of several YTX analogues to cause the accumulation of a 100 kDa MW fragment of E-cadherin in MCF-7 breast cancer cells. Under our experimental conditions, the EC(50) of YTX, the reference compound, was 0.55 nM. The introduction of a methylene unit adjacent to one of the sulfate groups, as is the case with the homoyessotoxin molecule, did not appear to greatly affect the potency of the analogue, as the measured EC(50) for this compound was 0.62 nM. The EC(50) values we measured for 45-hydroxyhomoyessotoxin and carboxyyessotoxin were about 9.4 and 26 nM, respectively, whereas the EC(50) of noroxoyessotoxin, lacking most of the C(9) chain, was about 50 nM. Thus, significant differences in the potencies of YTX analogues were found when structural changes involved the C(9) terminal chain of these compounds, leading to the conclusion that this portion of the molecule is essential for the activity of YTX in MCF-7 cells. A comparison of our findings with available information regarding the potency of YTX and its analogues in other experimental systems shows that the EC(50)'s we measured for the different compounds are up to 200-fold lower and vary in a wider concentration range. /It was speculated/ that YTX effects could involve two separate receptorial systems.
/ALTERNATIVE and IN VITRO TESTS/ .... the death response induced by yessotoxin (YTX) in cultured HeLa cells/was compared to/ that triggered by okadaic acid (OA) in the same experimental system. Sub-nanomolar concentrations of YTX were found to induce HeLa cell death after a 48-96-hr incubation. YTX caused loss of intact poly(ADP-ribose)-polymerase (PARP) in HeLa cells, and detection of the 85 kDa fragment, which is indicative of proteolytic attack by caspases. Measurements of caspase activities using extracts prepared from YTX-treated cells and substrates of the caspase-3/7 and caspase-2 isoforms, showed that the relative proteolysis of caspase-3/7 substrate was about eight-fold higher than that of caspase-2, the levels of which were about twice those measured with extracts from control cells. These findings were matched by Western blot analyses of caspase-2, -3 and -7 in HeLa cell extracts, which showed that the levels of pro-caspase-2 were not greatly affected by YTX treatment, whereas pro-caspase-3 and -7 were activated in YTX-treated cells. Taken together, these data complement others previously obtained with OA, and support the notion that caspase isoforms involved in cell death induced by OA and YTX are cell- and toxin-specific.
Four toxins, okadaic acid (OA), dinophysistoxin-1 (DTX1), pectenotoxin-6 (PTX6), and yessotoxin (YTX), all associated with diarrhetic shellfish poisoning (DSP), were administered via syringe to Scallops Patinopecten yessoensis and their distribution in the hepatopancreas, adductor muscle, and combined other tissues (mantle, gill, gonad) was analyzed by liquid chromatography-mass spectrometry. Toxins exclusively remained in the hepatopancreas irrespective of the injection site, adductor muscle or hepatopancreas. When injected into hepatopancreas, OA, DTX1, and YTX were metabolized to 7-O-palmitoylOA, 7-O-palmitoylDTX1 and 45-hydroxyyessotoxin (45OH-YTX), respectively. Such metabolic changes were insignificant when toxins were injected into the adductor muscle. The residual ratio for each toxin in the hepatopancreas was less than 20%. Mortalities of scallops treated with PTX6 were lower than those treated with other toxins.