T-2毒素的神经毒性及作用机制研究进展

T-2毒素是最具毒性的单端孢霉烯族化合物,是农产品中常见的污染物之一。饮食摄入是人类接触T-2毒素最常见的途径。T-2毒素暴露导致许多病理状况,如神经紊乱、心血管改变、免疫抑制和皮肤炎症。然而,T-2毒素导致的神经毒性尚不清楚,为了更全面地把握T-2毒素的神经毒性研究现状,本文对T-2毒素诱导神经毒性的可能作用机制进行了探讨。     

T-2毒素毒性分子作用机制与脱毒的研究进展

T-2毒素是一种A类单端孢霉烯族毒素,具有高度致毒作用、毒性较难降解等特点,严重威胁人类和动物安全。目前,用于T-2毒素脱毒的方法有物理吸附法、化学试剂中和法、微生物分解法等。但T-2毒素导致的中毒反应的分子机制还尚未明确,可能涉及多个方面,如线粒体损伤、细胞自噬、免疫逃逸、细胞凋亡等。因此,文章主要探讨了T-2毒素毒性作用分子机制以及T-2毒素脱毒的研究进展,为T-2毒素的深入研究提供参考。     

T-2毒素和HT-2毒素检测方法的研究进展

T-2毒素和HT-2毒素属于单端孢霉烯族毒素。T-2毒素是A类单端孢霉烯族毒素中毒性最强的一种真菌毒素,HT-2毒素为T-2毒素在体内与体外最为主要的代谢产物,二者在自然界中分布广泛。对T-2毒素和HT-2毒素检测方法的研究进展进行综述,对二者常见检测方法的优点和缺点进行分析,以期为T-2毒素和HT-2毒素检测方法的科学选择提供参考。     

家畜T-2毒素中毒的病因、症状与诊治

<正>1病因T-2毒素中毒是由单端孢霉烯族化合物中T-2毒素引起的,以患畜拒食呕吐及脏器出血为特征中毒性疾病。T-2毒素对家畜皮肤和黏膜具有直接刺激作用。毒素可引起家畜口腔、食道、胃肠道烧灼,造成口、唇、肠黏膜溃疡与坏死。由于胃肠道炎症,导致动物呕吐、腹泻、腹痛,体重下降,饲料利用率降低和生产性能下降等。T-2毒素对骨髓造血功能有较强地抑制作用,并可导致骨髓造血组织坏死,引起血细胞特     

T-2毒素的理化特性及其对家禽的毒害作用

T-2毒素是A类单端孢霉稀族毒素中毒性最强的一种真菌毒素,是多种镰刀菌的次级代谢产物,并广泛存在于谷物和动物饲料当中,T-2毒素也成为当前研究的热门课题之一。禽类对T-2毒素比较敏感,摄入剂量和接触时间不同会产生不同的毒性效应。根据不同的接触时间,禽类会出现急、慢性毒性作用,另一方面,T-2毒素能够引起禽类不同系统的毒性,包括消化系统毒性、免疫系统毒性、生殖系统毒性、神经系统毒性等。本文着重论述了T-2毒素的相关信息以及其对禽类的毒性作用。     

家畜 T-2毒素中毒的病因、症状与诊治

1病因T-2毒素中毒是由单端孢霉烯族化合物中T-2毒素引起的，以患畜拒食呕吐及脏器出血为特征中毒性疾病。T-2毒素对家畜皮肤和黏膜具有直接刺激作用。毒素可引起家畜口腔、食道、胃肠道烧灼，造成口、唇、肠黏膜溃疡与坏死。由于胃肠道炎症，导致动物呕吐、腹泻、腹痛，体重下降，饲料利用率降低和生产性能下降等。T-2毒素对骨髓造血功能有较强地抑制作用，并可导致骨髓造血组织坏死，引起血细胞特别是白细胞减少。T-2毒素可被迅速吸收进入血液循环，并产生细胞毒作用，损伤血管内皮细胞，破坏血管壁的完整性，使血管扩张、充血、通透性增高，引起全身各组织器官出血。T-2毒素可使血小板再生，血小板凝聚和释放功能发生障碍。     

单端孢霉烯族毒素抑制动物生长作用的研究进展

单端孢霉烯族毒素是主要的饲料污染物,包括T-2毒素、脱氧雪腐镰刀菌烯醇(DON)等,具有较强的毒性作用,能引起动物体多种病理变化。其毒性作用能改变真核翻译起始因子2α(EIF2α)、丝裂原激活的蛋白激酶(MAPK)、热休克蛋白90(Hsp90)、胰岛素样生长因子1(IGF-1)等细胞因子的活性,调节多种胺酰tRNA合成酶的活性,进而抑制蛋白质合成,阻滞动物生长。论文从单端孢霉烯族毒素对生长激素影响的角度,综述了该类毒素对动物生长的抑制作用,以期为阐明单端孢霉烯族毒素抑制动物生长的毒性作用机制奠定基础。     

饲料中T-2毒素的毒性作用研究进展

T-2毒素是由多种镰刀菌产生的单端孢霉烯族化合物中的一种毒素,广泛存在于谷物和饲料中。本文就饲料中T-2毒素的污染现状及其毒性作用作一综述。     

T-2毒素免疫毒性研究现状

T-2毒素的免疫毒性具有矛盾性和复杂性。低剂量T-2毒素可提升动物对病原体的抵抗力,高剂量T-2毒素则大大降低动物的免疫力。T-2毒素暴露时间早于病原体可增加动物免疫抵抗力,反之或毒素与病原体同时暴露,则降低动物对病原体的抵抗力。近期研究发现,细胞凋亡/存活通路维持毒素免疫调控动态平衡,自噬在免疫调控中发挥着关键而复杂的作用,但T-2毒素免疫调控中是否存在类似"免疫逃避"机制亟待研究。论文综述了T-2毒素免疫毒性的矛盾性,并重点讨论了其潜在的分子机制,为单端孢霉烯族毒素的免疫毒性和动物疫病防控研究提供参考。     

T-2毒素的毒性作用及其诱导细胞凋亡机制概述

T-2毒素是一种毒性作用很强的霉菌毒素,是以镰刀菌属为主要产毒菌株所产生的一种A类单端孢霉烯族毒素,在多种谷物中的污染水平较高,通过食物摄入后在人类和动物机体内产生一系列毒性作用,严重威胁人类和动物的健康。论文从T-2毒素的理化性质、产毒菌株、毒性作用及对细胞凋亡的作用机制进行了简述,重点介绍了T-2毒素在免疫系统、消化系统和肝脏毒性、神经和皮肤毒性、血液毒性、生殖毒性方面的研究进展,以及T-2毒素通过线粒体信号通路介导细胞凋亡机制的研究进展,为T-2毒素的深入研究提供参考。     

Selection and Evaluation of Indexes Commonly Used to Determine Contamination with T-2 Toxin in Pacific White Shrimp Litopenaeus vannamei by the Grey Relational Method

Abstract

The objectives of the present study were to evaluate the effects of different concentrations of the mycotoxin T-2 toxin in feed on muscle performance in the Pacific white shrimp Litopenaeus vannamei, evaluate indexes of physiological variables that indicate T-2 toxin contamination in the shrimp using the grey relational method, and determine the dose–response relationships between T-2 toxin and the indexes. Of the 6 physical, 7 biochemical, and 17 nutritional indexes examined, the values of the grey relational coefficients were highest for the hepatopancreas: body weight ratio (HBR), alanine aminotransferase (ALT) activity, and serine (SER) content (0.83, 0.68, and 0.82, respectively). Therefore, the HBR, ALT activity, and SER content were selected as appropriate indexes for contamination of Pacific white shrimp muscle with T-2 toxin. Based on their dose–response relationship curves, mean effective doses of 1.45, 1.69, and 1.33 mg of T-2 toxin/kg of feed were obtained for the HBR, ALT activity, and SER content, respectively. These results offer technical reference points for the evaluation and control of T-2 toxin in shrimp feed.

Received April 28, 2016 accepted April 9, 2017 Published online July 26, 2017     

Determination of the acute 50% lethal dose T-2 toxin in adult bobwhite quail: additional studies on the effect of T-2 mycotoxin on blood chemistry and the morphology of internal organs

Three experiments were conducted to assess mortality rate, blood chemistry, and histologic changes associated with acute exposure to T-2 mycotoxin in adult bobwhite quail. In Experiment 1, adult quail were orally dosed with T-2 toxin to determine the lethal dose that resulted in 50% mortality of the affected population (LD50), and that dose was determined to be 14.7 mg of T-2 toxin per kilogram of body weight (BW). A second experiment was performed to study the effects of 12-18 mg/kg BW T-2 toxin on blood chemistry and liver enzyme profiles. Posttreatment uric acid, aspartate aminotransferase, lactic dehydrogenase, and gamma glutamyltransferase increased as compared with pretreatment values. In contrast, posttreatment plasma total protein, cholesterol, and triglyceride levels numerically decreased as compared with pretreatment values. Changes in blood chemistry values were consistent with liver and kidney damage after T-2 toxin exposure. In Experiment 3, histologic analyses of bone marrow, spleen, liver, small intestine, kidney, and heart were conducted on birds dosed in Experiment 2. Marked lymphocyte necrosis and depletion throughout the spleen, thymus, bursa, and gut-associated lymphoid tissue in the small intestine were observed in birds dosed with 15 and 18 mg/kg BW T-2 toxin. Necrosis of liver and lipid accumulation as a result of malfunctioning hepatocytes were also observed. Little or no morphologic change was observed in bone marrow and heart tissue. The LD50 for adult bobwhite quail as found in this study is two to three times higher than that reported for other species of commercial poultry. Results from these data confirm previous reports of immunosuppressive and/or cytotoxic effects of T-2 toxin in other mammalian and avian species. T-2 toxin may have a negative impact on the viability of wild quail populations.     

Embryotoxic effects of prenatal T-2 toxin exposure in mice.

Pregnant CD-1 mice were administered T-2 toxin by gastric intubation on day 11 of gestation at dosages of 0, 0.75 and 1.5 mg/kg. The T-lymphocyte dependent antibody response against sheep red blood cells which was evaluated in the offspring at six weeks of age was not affected by T-2 toxin exposure. Individual birth and weaning weights were not influenced by T-2 toxin, but the litter size was reduced in the high dose group, without affecting the number of implantation sites per dam. The number of female offspring produced by dams exposed to 1.5 mg/kg T-2 toxin was less compared to other treatment groups, suggesting that the female fetus was more susceptible to embryolethal effects of prenatal T-2 toxin exposure. These results suggest that prenatal T-2 toxin exposure is unlikely to be a significant health problem with respect to primary humoral immunity. At the dosages given, T-2 toxin produced substantial embryotoxicity without alteration in antibody production. The embryolethal effects are a primary limiting factor which may preclude the expression of any immunoteratological manifestations associated with humoral immunity under natural field conditions.     

T-2 toxin induced Salmonella Typhimurium intoxication results in decreased Salmonella numbers in the cecum contents of pigs, despite marked effects on Salmonella-host cell interactions

ABSTRACT: The mycotoxin T-2 toxin and Salmonella Typhimurium infections pose a significant threat to human and animal health. Interactions between both agents may result in a different outcome of the infection. Therefore, the aim of the presented study was to investigate the effects of low and relevant concentrations of T-2 toxin on the course of a Salmonella Typhimurium infection in pigs. We showed that the presence of 15 and 83 μg T-2 toxin per kg feed significantly decreased the amount of Salmonella Typhimurium bacteria present in the cecum contents, and a tendency to a reduced colonization of the jejunum, ileum, cecum, colon and colon contents was noticed. In vitro, proteomic analysis of porcine enterocytes revealed that a very low concentration of T-2 toxin (5 ng/mL) affects the protein expression of mitochondrial, endoplasmatic reticulum and cytoskeleton associated proteins, proteins involved in protein synthesis and folding, RNA synthesis, mitogen-activated protein kinase signaling and regulatory processes. Similarly low concentrations (1-100 ng/mL) promoted the susceptibility of porcine macrophages and intestinal epithelial cells to Salmonella Typhimurium invasion, in a SPI-1 independent manner. Furthermore, T-2 toxin (1-5 ng/mL) promoted the translocation of Salmonella Typhimurium over an intestinal porcine epithelial cell monolayer. Although these findings may seem in favour of Salmonella Typhimurium, microarray analysis showed that T-2 toxin (5 ng/mL) causes an intoxication of Salmonella Typhimurium, represented by a reduced motility and a downregulation of metabolic and Salmonella Pathogenicity Island 1 genes. This study demonstrates marked interactions of T-2 toxin with Salmonella Typhimurium pathogenesis, resulting in bacterial intoxication.     

The occurrence of a toxigenic strain of Fusarium tricinctum in connection with disease in a dairy cow]

The fungus Fusarium tricinctum, producing T-2 toxin, was isolated from mouldy maize silage. T-2 toxin was identified by TLC and by a bioassay. Consumption of mouldy silage resulted in a disease in a dairy cow, which had to be killed. The patho-anatomical findings obtained in the slaughtered cow generally suggested trichothecene poisoning. It was derived from these findings that the disease was due to the presence of trichothecenes in the feed.     

Effect of fusarium T-2 toxin on hematological and biochemical parameters in the rabbit.

The single intravenous administration of purified T-2 toxin to rabbits to 0.5 mg per kg body weight produced a decrease in hematocrit, while blood cell count, and serum alkaline phosphatase activity. The plasma clotting time, as measured by the activated partial thromboplastin time assay, was prolonged after intravenous T-2 toxin administration. In contrast, the administration of T-2 toxin to rabbits at 2.0 mg per kg body weight by gastric intubation produced oral lesions, diarrhea and anorexia in the animals but did not cause significant alteration in hematological and biochemical parameters. The results suggest that the rabbit may be a suitable model for further examination of the biochemical mechanisms involved in the cytotoxic action of T-2 toxin.     

Fatal placental hemorrhage in pregnant CD-1 mice following one oral dose of T-2 toxin.

Forty-eight hours after oral administration of a single dose (3.0 mg/kg BW) of T-2 toxin to mice on days 7, 8, 10, 11 and 12 of pregnancy, 17% maternal mortality following vaginal hemorrhage was encountered. Necropsy examination of the dead females revealed that massive hemorrhages originating from the placental regions had occurred into the reproductive tract. This observation supports the studies in which hemorrhagic disease has been described as characteristic for intoxications with T-2 toxin. The results suggest that fatal hemorrhage during pregnancy can occur in hemochorial and hemoendotheliochorial placental mammals as a result of T-2 toxin administration.     

Interaction of T-2 fusariotoxin and monensin in broiler chickens infected with Coccidia

Field observations suggest that coccidiosis is a common cause of death in broiler chicken flocks fed diets containing sufficient amounts of ionophore antibiotics (monensin, narasin, etc.) and contaminated with mycotoxins, particularly with T-2 fusariotoxin. To study this phenomenon, broiler chickens fed diets containing different amounts of T-2 toxin and free from monensin, or containing a preventive dose (100 mg/kg of feed) of monensin, were infected experimentally with coccidian oocysts. In all groups fed a diet containing monensin plus T-2 toxin severe clinical symptoms of coccidiosis (blood-stained faeces etc). occurred. Deaths and retarded growth depended on the toxin dose and were considerable. The body mass gain of chicks fed a diet containing monensin and T-2 toxin but not infected with coccidia was inferior to that of groups fed diets which contained either monensin or T-2 toxin (experiment 2). On the basis of these findings a negative interaction of the two compounds is assumed. This seems to be supported by the results of experiment 3, i. e. the finding that the lethal dose of narasin, a compound closely related to monensin both in chemical structure and mechanism of action, proved to be much lower (LD50 = 102 mg/kg body mass) for chickens fed a diet supplemented with T-2 toxin than for the control chickens (LD50 = 176 mg/kg body mass). The present results suggest that the feeding of diets severely contaminated with T-2 toxin may alter the anticoccidial efficacy of monensin.     

The fungal T-2 toxin alters the activation of primary macrophages induced by TLR-agonists resulting in a decrease of the inflammatory response in the pig

T-2 toxin is known to be one of the most toxic trichothecene mycotoxins. Exposure to T-2 toxin induces many hematologic and immunotoxic disorders and is involved in immuno-modulation of the innate immune response. The objective of this work was to evaluate the effects of T-2 toxin on the activation of macrophages by different agonists of Toll-like receptors (TLR) using an in vitro model of primary porcine alveolar macrophages (PAM). Cytotoxic effects of T-2 toxin on PAM were first evaluated. An IC₅₀ of 19.47 ± 0.9753 nM was determined for the cytotoxicity of T-2 toxin. A working concentration of 3 nM of T-2 toxin was chosen to test the effect of T-2 toxin on TLR activation; this dose was not cytotoxic and did not induce apoptosis as demonstrated by Annexin/PI staining. A pre-exposure of macrophages to 3 nM of T-2 toxin decreased the production of inflammatory mediators (IL-1 beta, TNF-alpha, nitric oxide) in response to LPS and FSL1, TLR4 and TLR2/6 agonists respectively. The decrease of the pro-inflammatory response is associated with a decrease of TLR mRNA expression. By contrast, the activation of TLR7 by ssRNA was not modulated by T-2 toxin pre-treatment. In conclusion, our results suggest that ingestion of low concentrations of T-2 toxin affects the TLR activation by decreasing pattern recognition of pathogens and thus interferes with initiation of inflammatory immune response against bacteria and viruses. Consequently, mycotoxins could increase the susceptibility of humans and animals to infectious diseases.