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.     

Ovine platelet function and its inhibition by T-2 toxin

Ovine platelets suspended in homologous plasma aggregated effectively in response to adenosine-diphosphate, acid-soluble collagen and aggregated moderately to serotonin and arachidonic acid. Ovine platelet aggregation, in response to each agent, was inhibited in a concentration dependent fashion by T-2 toxin. The platelet aggregates which formed in the presence of T-2 toxin appeared to be less stable than aggregates in comparable control platelet suspensions.     

Subacute toxic effects of dietary T-2 toxin in young mallard ducks.

Young Mallard ducks (Anas platyrhynchos) were fed diets containing purified T-2 toxin at levels of 20 or 30 ppm for two or three weeks. Ingestion of T-2 toxin was associated with reduced weight gain and delayed development of adult plumage. Affected ducks developed caseonecrotic plaques throughout the upper alimentary tract, especially in oropharynx and ventriculus. Several ducks also developed severe ulcerative, proliferative esophagitis and proventriculitis. Generalized atrophy of all lymphoid tissues consistently occurred. The manifestations of T-2 mycotoxicosis in Mallard ducks were mostly attributable to irritant toxicity to the alimentary mucosa. The T-2 toxin caused neither hematopoietic suppression nor a hemorrhagic syndrome in ducks. These alimentary lesions of T-2 mycotoxicosis in ducks do not resemble diseases of native waterfowl presently being recognized in routine surveillance of waterfowl mortality in Saskatchewan.     

Mycotoxicosis caused by aerosolized T-2 toxin administered to female mice

Thymus, spleen, adrenal glands, and small intestine of female mice exposed to aerosolized T-2 mycotoxin were examined at postexposure hours (PEH) 0.25, 1, 2, 4, 6, 9, 12, and 24. Lymphocyte necrosis was observed at PEH 1 in the thymus, spleen, and lamina propria and Peyer patches of the small intestine. Necrosis of small intestinal crypt epithelial cells was observed at PEH 2, and necrosis of parenchymal cells and increased number of neutrophils were seen in sinusoids of the adrenal cortex at PEH 4. These results indicated that the earliest microscopic evidence of T-2 mycotoxicosis after aerosol exposure was necrosis of lymphocytes in the thymus, spleen, and lamina propria and Peyer patches of the small intestine.     

Regulation of murine macrophage phagocytosis of sheep erythrocytes by T-2 toxin

The effect of a single oral dose of 4 mg of T-2 toxin/kg of body weight on in vivo phagocytosis of sheep RBC by peritoneal macrophages was evaluated in nonsensitized mice and in mice sensitized with sheep RBC. T-2 toxin treatment had no effect on the viability or phagocytic activity of resident peritoneal macrophages in nonsensitized mice. However, a significant (P less than 0.005) increase in phagocytic activity occurred in cells from mice treated with toxin and subsequently sensitized with sheep RBC. In contrast, phagocytosis of sheep RBC was significantly (P less than 0.05) suppressed in cells from mice treated with toxin after sensitization. Toxin treatment induced necrosis of lymphocytes and significant decreases in thymus and spleen weights. Seemingly, T-2 toxin, administered at a dose that caused marked lymphoid depletion, suppressed or enhanced in vivo macrophage phagocytic activity in antigenically sensitized mice, and enhancement or suppression of phagocytosis was a function of the time of toxin treatment in relation to antigenic stimulation.     

Effects of treatment of growing swine with aflatoxin and T-2 toxin

Effects of dietary aflatoxin (AF) and T-2 toxin, singly and in combination, were evaluated in growing crossbred (Yorkshire x Landrace x Hampshire) pigs. The experimental design consisted of 4 treatment groups of 6 barrows each fed diets containing 0 mg of AF and T-2/kg of feed (controls; group 1), 2.5 mg of AF/kg of feed (group 2), 10 mg of T-2/kg of feed (group 3), or 2.5 mg of AF plus 10 mg of T-2/kg of feed (AF + T-2; group 4) ad libitum for 28 days (7 to 11 weeks of age). Production performance, and serum biochemical, and hematologic evaluations were made weekly. Body weight and body weight gain were depressed by all toxin treatments, but the effect of AF and T-2 toxin in combination was less than additive. Liver and kidney weights, as a percentage of body weight, were increased by AF treatment, and heart weight, as a percentage of body weight, was increased by T-2 treatment. Treatment with T-2 toxin induced necrotizing contact dermatitis on the snout, buccal commissures, and prepuce. Consumption of AF resulted in increased serum activities of alkaline phosphatase, aspartate transaminase, cholinesterase, and gamma-glutamyltransferase, and decreased serum concentrations of urea nitrogen, cholesterol, albumin, total protein, calcium, potassium, magnesium, and phosphorus. Consumption of T-2 toxin resulted in increased serum triglyceride concentration and decreased serum iron concentration. Treatment with AF induced lower serum unsaturated iron-binding capacity and high RBC count, PCV, hemoglobin concentration, WBC count, and prothrombin time.(ABSTRACT TRUNCATED AT 250 WORDS)     

T-2毒素对大鼠离体培养卵巢颗粒细胞凋亡的影响

将未成熟的Wistar大鼠卵巢颗粒细胞进行原代培养,用不同浓度的T-2毒素染毒细胞24 h.染毒结束后,采用MTT法检测细胞相对活力,荧光染料Hoechst 33258检测卵巢颗粒细胞的凋亡变化,RT-PCR检测凋亡调控基因Bcl-2、Bax和P53 mRNA的表达.结果显示,随着T-2毒素染毒剂量的增加,颗粒细胞的细胞活力逐渐下降;而细胞凋亡率、Bcb2、Bax、P53 mRNA表达水平、Bax mRNA/Bcl-2 mRNA比值则逐渐上升;除1 nmol/L剂量组外,其余各剂量组与对照组比较差异显著(P＜0.05).结果表明,T-2毒素可显著抑制大鼠卵巢颗粒细胞活力,诱导颗粒细胞凋亡,并呈浓度依赖关系.     

Effect of T-2 toxin on brain biogenic monoamines in rats and chickens.

Two experiments were conducted to determine the effect of T-2 toxin on brain biogenic monoamines and their metabolites. Male rats (180 g) and cockerels (28 day, 300 g) were orally dosed with T-2 toxin at 2.5 mg kg-1 body weight. In the first experiment, whole brains were collected 2, 6, 12, 24 and 48 h postdosing and analyzed for monoamines by high performance liquid chromatography with electro-chemical detection. T-2 toxin did not influence whole brain concentrations of monoamines in either species. In the second experiment, brains were collected 24 h postdosing, dissected into five brain regions, and analyzed for monoamines. T-2 toxin treatment resulted in increased serotonin and 5-hydroxy-3-indoleacetic acid in all brain regions of the rat. However, this was not seen in poultry where T-2 toxin treatment resulted in an increase in 5-hydroxy-3-indoleacetic acid, no alteration in serotonin concentration and a decrease in regional norepinephrine and dopamine concentrations. These results suggest that T-2 toxin influences brain biogenic amine metabolism and that there is an intraspecies difference in the central effects of this mycotoxin.     

Effect of T-2 toxin on egg production and hatchability in laying hens.

The effect of diets containing different levels of T-2 toxin on egg production and hatchability was studied in a four-week experiment using 100 laying hens of the SSL hybrid line and 10 cocks divided into 10 groups. Another aim of the experiment was to investigate how effectively the increased dietary vitamin E content neutralized the adverse effects of T-2 toxin. The diet of the control group (C) contained no mycotoxin, while those of the experimental groups included the following levels of T-2 toxin: groups 1, 2 and 3: 1 mg/kg, groups 4, 5 and 6: 5 mg/kg; groups 7, 8 and 9: 10 mg/kg. Vitamin E was added to the diet of groups C, 1, 4 and 7 at a rate of 50 mg/kg while to that of groups 2, 5 and 8 at a rate of 100 mg/kg. To the diet of groups 3, 6 and 9 no vitamin E was added. Contamination of the diet with T-2 toxin markedly decreased egg production and impaired hatchability. The production decrease was proportional to the T-2 toxin concentration of the diet. Increased dietary vitamin E concentration exerted no influence on egg production. However, during the first week of the experiment it significantly (P < 0.01) decreased the number of infertile eggs and significantly (P < 0.01) improved the hatching percentage. Dietary vitamin E concentration was in positive correlation with the hatching percentage; this correlation was rather close (r = 0.74) in the first week of the experiment.     

T-2毒素对Sertoli细胞氧化应激和DNA损伤作用的研究

用不同浓度的T-2毒素染毒Sertoli细胞24h。染毒结束后采用MTT法检测细胞相对活力,常规方法检测SOD、过氧化氢酶(CAT)和谷胱肽过氧化物酶(GSH-Px)活性以及丙二醛(MDA)含量,彗星试验检测DNA损伤。结果显示,与对照组比较,随着T-2毒素染毒剂量的增加,Sertoli细胞的超氧化物歧化酶(SOD)、CAT和GSH-Px活性显著下降(P<0.05),MDA含量显著上升(P<0.05),DNA的损伤程度则加重的极为显著(P<0.01)。结果表明,T-2毒素可显著抑制Sertoli细胞活力,并通过氧化应激损伤细胞的DNA。     

Subacute toxicity of Dietary T-2 toxin in mice: influence of protein nutrition.

The subacute toxic effects of dietary T-2 toxin (20 ppm) incorporated in semipurified diets of 8%, 12% or 16% protein, were examined in young Swiss mice after one, two, three and four weeks. Dietary T-2 toxin caused substantial reductions in growth and food consumptaion, the degrees of which were greatest in mice fed the diets of reduced protein content. T-2 toxin consistently caused similar degrees of nonregenerative anemia, lymphopenia, thymic atrophy and gastric hyperkeratosis irrespective of the dietary protein level. However, erythroid hypoplasia was temporary in mice fed T-2 toxin in the 16%-protein diet such that erythroid precursors regenerated in splenic and bone marrow and were hyperplastic after four weeks. Liver to body weight ratios of mice fed T-2 toxin in the 16%-and 12%-protein diets increased during the four week trial in comparison to control mice fed at a similar rate. These observations indicated that suppression of erythropoiesis in mice by dietary T-2 toxin was temporarty and that the interval before regeneration was prolonged by diets of reduced protein content.     

Subacute toxicity of dietary T-2 toxin in mice: morphological and hematological effects.

Changes in hematopoietic and lymphoid tissues of young Swiss mice fed a balanced semipurified diet containing T-2 toxin (20 ppm) were examined after one, two, three, four or six weeks. During the first three weeks of exposure of T-2 toxin, lymphoid tissues, bone marrow and splenic red pulp became hypoplastic, resulting in anemia, lymphopenia and eosinopenia. Subsequently, during continued exposure to T-2 toxin, hematopoietic cells regenerated in bone marrow and splenic red pulp and became hyperplastic by six weeks. Granulopoiesis and thrombopoiesis resumed in advance of erythropoiesis. All lymphoid tissues remained atrophic throughout the six week trial. Mice exposed to T-2 toxin also developed perioral dermatitis and hyperkeratosis with ulceration of the mucosa of the esophageal region of the stomach. These results indicated that young mice were susceptible to both the irritant and the hematopoietic-suppressive toxic effects of dietary T-2 toxin. However, supression of hematopoiesis was transient and did not lead to hematopoietic failure.     

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.     

The effect of T-2 toxin on the bovine immune system: Cellular factors

The effect of T-2 toxin, a Fusarium metabolite, on the bovine cellular defense (immune) system was evaluated during high level, chronic administration. The administration of T-2 toxin to calves at the rate of 0.6 mg/kg/day was associated with significant depression of lymphocyte responses to mitogens and significant decreases in chemotaxic migration of neutrophils.