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首页> 外文期刊>Journal of Agricultural and Food Chemistry >Ingested Shiga Toxin 2 (Stx2) Causes Histopathological Changes in Kidney, Spleen, and Thymus Tissues and Mortality in Mice
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Ingested Shiga Toxin 2 (Stx2) Causes Histopathological Changes in Kidney, Spleen, and Thymus Tissues and Mortality in Mice

机译:摄入志贺毒素2(Stx2)导致小鼠肾脏,脾脏和胸腺组织的组织病理学变化以及死亡率

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The Shiga toxin (Stx)-producing bacterial strain, Escherichia coli O157:H7, colonizes the distal small intestine and the colon, initiating serious illness, including hemolytic-uremic syndrome (HUS), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Although intravenous administration of purified Stx to primates has been able to reproduce the features of HUS, it has not been conclusively established as to whether ingestion of Stx alone without the bacterium poses a potential health risk. To help answer this question, in this study, we fed Shiga toxin 2 (Stx2) directly into the stomachs of mice via gavage. Our data show that ingestion of Stx2 at a concentration of 50 μg/ mouse induces weight loss and kills the mice at 3-5 days post-gavage. Additional studies revealed that the toxin retains activity at low pH, that its activity is neutralized by treatment with toxin-specific antibody, and that about 1% of the fed toxin is absorbed into the blood circulation. Lethality by intraperitoneal (IP) injection of Stx2 occurred at much lower doses than by ingestion. Detailed histopathological evaluation of stained tissues by light microscopy revealed severe histopathological changes in kidneys, spleen, and thymus but not in the pancreas, lymph nodes, heart, lungs, trachea, esophagus, stomach, duodenum, jejunum, ileum, cecum, and colon. The pathological changes in the kidney appeared similar to those seen in humans with HUS. The cited data suggest that (a) most but not all of the toxin is inactivated in the digestive tract, (b) part of the oral-ingested toxin is absorbed from the digestive tract into the circulation, (c) enough active toxin reaches susceptible organs to induce damage, and (d) Stx2 in the absence of toxin-producing bacteria can be harmful to mice. The results are clinically relevant for food safety because we also found that heat treatments (pasteurization) that destroy bacteria did not inactivate the heat-resistant toxin produced and secreted by the bacteria.
机译:产生志贺毒素(Stx)的细菌菌株O157:H7大肠杆菌定植于远端小肠和结肠,引发了严重的疾病,包括溶血性尿毒症综合征(HUS),其特征是微血管性溶血性贫血,血小板减少症和急性肾病失败。尽管向灵长类动物静脉内注射纯化的Stx能够重现HUS的特征,但尚未确定是否在没有细菌的情况下单独摄入Stx是否构成潜在的健康风险。为了帮助回答这个问题,在这项研究中,我们通过管饲法将志贺毒素2(Stx2)直接喂入小鼠的胃中。我们的数据表明,以50μg/小鼠的浓度摄入Stx2会导致体重减轻,并在灌胃后3-5天杀死小鼠。进一步的研究表明,该毒素在低pH值下仍保留活性,通过用毒素特异性抗体进行处理可以中和该毒素的活性,并且大约1%的进食毒素被吸收到血液循环中。腹膜内(IP)注射Stx2致死的剂量远低于摄入。通过光学显微镜对染色的组织进行详细的组织病理学评估,发现肾脏,脾脏和胸腺有严重的组织病理学改变,而胰腺,淋巴结,心脏,肺,气管,食道,胃,十二指肠,空肠,回肠,盲肠和结肠则没有严重的组织病理学改变。肾脏的病理变化似乎与HUS患者相似。引用的数据表明:(a)大部分但不是全部毒素在消化道中被灭活,(b)口腔摄取的毒素的一部分从消化道吸收到循环中,(c)足够的活性毒素易感(d)在没有产生毒素的细菌的情况下,Stx2可能对小鼠有害。该结果在临床上与食品安全相关,因为我们还发现破坏细菌的热处理(巴氏灭菌)不会使细菌产生和分泌的耐热毒素失活。

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