Enhanced resistance to listeriosis induced in mice by preinoculation treatment with T-2 mycotoxin

The effect of T-2 toxin on cell-mediated resistance to bacterial infection was evaluated in mice challenge exposed with Listeria monocytogenes. Mice were treated orally on days -5, -4, -3, -2, -1, +1, and +3 with 2.0, 1.0, 0.5, or 0 mg of T-2 toxin/kg of body weight and were exposed to 10(6) (LD100) or 10(5) (LD50) L monocytogenes by intraperitoneal injection on day 0. Necrosis and depletion of lymphocytes in the thymus and spleen, decrease in thymus weight, reductions in the number of circulating total leukocytes and lymphocytes, and necrotizing gastroenteritis occurred in the toxin-treated mice. Although the cytotoxic effect of T-2 toxin on lymphoid tissue was marked, enhanced resistance to Listeria infection was revealed by significant (P less than 0.01) decreases in mortality caused by listeriosis in the toxin-treated mice. Mortality decreased from 100% to 64% in the mice exposed to 10(6) Listeria and from 50% to 20% in the mice exposed to 10(5) Listeria. Percentage of mortality after Listeria challenge exposure was dependent on the T-2 toxin dose and was progressively decreased in the mice given 0.5, 1.0, or 2.0 mg of toxin/kg.     

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。     

Effects of T-2 mycotoxin on tumor susceptibility in mice

The effect of Fusarium-produced T-2 toxin on tumor growth was evaluated in ICR, CFW, and C57B6/6 mice inoculated with murine sarcoma, Ehrlich ascites carcinoma, or B16F1 melanoma tumor cell lines. Mice were given T-2 toxin intragastrically either at the rate of 2 mg of toxin/kg of body weight daily for 5 days or a single dosage of 4 mg of toxin/kg and were inoculated SC with tumor cells 1 or 2 days after administration of toxin. Tumor growth was assessed 15 to 41 days after tumor challenge by determining the frequency of tumor development and tumor weights. Significant increases in the frequency of development of murine sarcoma (P less than 0.005), Ehrlich ascites carcinoma (P less than 0.01), and B16F1 melanoma tumors (P less than 0.05) were detected in toxin-treated mice, compared with control mice. Murine sarcoma and B16F1 melanoma tumor weights also were significantly (P less than 0.01) higher in toxin-treated mice. The effect of T-2 toxin on tumor growth was more marked after 5 daily treatments than after a single dose.     

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.     

Evaluation of two mycotoxin binders to reduce toxicity of broiler diets containing ochratoxin A and T-2 toxin contaminated grain

In order to assess ochratoxin A (OA) and T-2 toxin (T-2) binding ability of two commercial sorbents, both in vitro and in vivo trials with broilers were performed. Crude OA and T-2 extracts from contaminated grain were used to assess in vitro binding ability of two sorbents (Zeotek [Zk] and Mycofix [Mx]), by quantifying free mycotoxin through an enzyme-linked immunosorbent assay (ELISA) test. For in vivo trial, a 3 x 2 x 2 factorial arrangement was used for this experiment, being the factors: adsorbents (none, Zk, and Mx), OA (0 and 567 parts per billion [ppb]) and T-2 (0 and 927 ppb). OA and T-2 contaminated wheat and corn, respectively, were added to sorghum-soybean meal diets to meet 567 ppb of OA and 927 ppb of T-2. Mycotoxins were fed alone or combined in treatments. After 21 days, blood chemistry, gross, and histological evaluations were performed. Relative weights of liver, kidney, and bursa of Fabricius were obtained. Zk had the highest OA and T-2 in vitro binding ability (100% and 8.67%, respectively). Chickens fed OA with or without sorbents had a lower body weight and feed intake reduction. However, those birds fed T-2 were partly protected by a sorbent. Birds fed both toxins showed toxic additive effects, and no protection of any adsorbent was observed. A significant reduction in plasma proteins, albumin, and globulins was a characteristic observed in all birds fed diets with OA both with or without adsorbents. Uric acid level in blood was increased in all chickens fed OA-contaminated diets. Histological findings observed in birds fed OA-contaminated diets were necrosis of kidney tubular cells, swollen and necrotic hepatocytes, bile ducts hyperplasia, and increased diameter of proventriculus glands. In birds that received T-2 alone, only the liver, with the same kind of lesions, was affected. According to these results, it can be concluded that there is not a relation between in vitro and in vivo trials. OA toxic effects could not be counteracted by any sorbent. T-2 toxicity could be partially counteracted by an adsorbent used in this research.     

Perivascular eosinophilic droplets in swine brain induced by Escherichia coli toxin.

Pigs inoculated intravenously with the culture supernatant and extract of Escherichia coli were investigated histologically. Perivascular eosinophilic droplets and slight vascular degeneration were observed in the medulla oblongata, mid-brain and pons. These droplets were negative for periodic acid-Schiff staining.     

Muscovy ducklings, a particularly sensitive avian bioassay for T-2 toxin and diacetoxyscirpenol

Day-old domesticated Muscovy ducklings (Cairina moshata) were given the trichothecene mycotoxins T-2 toxin or diacetoxyscirpenol at 0.25, 0.5, or 1 micrograms/g of feed for 7 days. All concentrations of both toxins caused characteristic dose-related lesions on the roof of the oral cavity of the birds. Muscovy ducklings showed these signs in a shorter time (less than 16 hours in some cases) and at a lower feed concentration of these trichothecenes than did other avian species in similar studies.     

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.     

Acute toxicological experiment of T-2 toxin in rabbits

Rabbits were treated with a single oral dose (1, 2, 4, 6, 8, 10 or 15 mg/kg body mass) of T-2 fusariotoxin. Doses of 4 mg or higher killed the animals in 24 to 48 h. As opposed to the controls, in the treated rabbits gross pathological and histopathological examinations revealed acute catarrhal gastroenteritis, necrosis of lymphoid cells of the gastrointestinal mucosa, centrolobular dystrophy of the liver, necrosis of cells of the mononuclear phagocyte system (MPS) in the liver, tubulonephrosis, focal dystrophy of the adrenal cortex, lymphocyte depletion involving both T- and B-cell-dependent zones of the lymphoid organs (spleen, lymph, ampulla ilei), and depletion and necrosis of the myelopoietic cell colonies of the bone marrow. Similar but milder changes were observed in surviving rabbits exsanguinated 48 h after treatment. In addition to the direct damage done to the digestive tract mucosa and liver, the toxin severely damaged the cells participating in humoral and cell-mediated immunity and in the local defence of the intestinal mucosa, and markedly impaired phagocytosis and granulocytopoiesis. In another experiment rabbits were given oral doses of 2 mg/kg body mass T-2 toxin daily for several days. One rabbit was killed by bleeding every day. In rabbits killed beyond day 7 there was subacute catarrhal gastritis, emaciation, and hypertrophy of the adrenal cortex.     

Cleavage of zearalenone-glycoside, a "masked" mycotoxin, during digestion in swine

Comparative analyses of cereal samples pretreated with or without beta-glucosidase indicate the presence of zearalenone-glycoside. To examine the stability of zearalenone-glycoside during digestion, mixed feed was artificially contaminated with synthesized zearalenone-4-beta-D-glucopyranoside (395 micrograms/kg) and fed to a pig over a period of 14 days. The metabolites detected in feces and urine samples were zearalenone and alpha-zearalenol. These results demonstrate that zearalenone-4-beta-D-glucopyranoside is decomposed during digestion and the aglucone, zearalenone, is released. Since zearalenone-glycoside is not detected during routine analysis, but hydrolysed during digestion, it seems likely that such "masked mycotoxins" are involved in cases of mycotoxicoses.     

Quantitative morphology of peracute pulmonary lesions in swine induced by Haemophilus pleuropneumoniae

Twenty-seven six-week-old cesarean-derived, colostrum-deprived pigs were inoculated intratracheally with an isolate of Haemophilus pleuropneumoniae serotype 5 (principles) of high virulence (I-200) or low virulence (B-8) or phosphate buffered saline (controls). Pigs given I-200 had severe serofibrinous pleuropneumonia at three hours after inoculation; two of three pigs were dead by 24 hours after inoculation. Interalveolar septa in the caudal lung lobes were 41% thicker than septa from control pigs at three hours after inoculation and 79% thicker by 24 hours after inoculation. Interalveolar septal capillaries in caudal lung lobes were 10.2% larger than control capillaries at three hours after inoculation and 25.6% larger by 24 hours after inoculation. Interalveolar septal capillary platelet volume was greater than the platelet volume of controls; 70% of these platelets were aggregated. There was severe diffuse alveolar, interalveolar septal, and interlobular septal edema at three hours after inoculation with fibrin, neutrophils, and macrophages present in later samples. Thirty-three percent of the lung parenchyma was necrotic at 24 hours after inoculation. Endothelial cell degeneration was generally mild, but necrotic in regions of pulmonary infarction. Pigs inoculated with the B-8 isolate did not develop marked macroscopic lesions at any sampling time. Interalveolar septa were 18% thicker than controls nine hours after inoculation and 5% thicker at six and 24 hours after inoculation. Capillary platelet volume was greatest at nine hours after inoculation with 50% of these platelets aggregated; 30% of the platelet volume was aggregated at the 24-hour sample period. Moderate diffuse pulmonary and interlobular septal edema was present at three, six, and nine hours after inoculation, but absent 24 hours after inoculation. Intravascular macrophages were present in the six, nine, and 24-hour lung samples in both B-8 and I-200 inoculated pigs. These cells were adherent to interalveolar septal capillary endothelial cells and contained phagocytized cellular debris and fibrin. These results indicate the early effects of H. pleuropneumoniae infection involve macrophage and platelet activation, and a marked increase in interalveolar septal capillary permeability.     

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.     

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.