Myocardial and pancreatic lesions induced by T-2 toxin, a trichothecene mycotoxin, in swine

Myocardial and pancreatic lesions induced by sublethal doses of T-2 toxin in swine were characterized by light and electron microscopy. Toxin was given intravenously to six 17- to 18-week-old pigs. Pigs were killed 24 or 48 hours after treatment. Grossly, subendocardial hemorrhages, multifocal pinpoint white foci in myocardium, and pancreatic edema occurred in one treated pig. Histologic changes in myocardium of treated pigs consisted of multifocal edema, mononuclear cell infiltration, myofiber hyalinization, vacuolation, and contraction bands with nuclear pyknosis. Ultrastructurally, there were areas of edema, myofibrillar disorganization, dilation of sarcoplasmic reticulum, and formation of hypercontraction bands. Myocardial mineralization was seen in the pig with gross lesions. Pancreatic changes in treated pigs consisted of multifocal acinar degeneration and necrosis. Ultrastructural changes included irregular dilation of rough endoplasmic reticulum and abnormal zymogen granules. Thus, in addition to radiomimetic lesions of the gastrointestinal tract and lymphoid organs, heart and pancreas are target organs of T-2 toxin in swine.     

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.     

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.     

Characterization of the toxicity of the mycotoxins aflatoxin, ochratoxin, and T-2 toxin in game birds. I. Chukar partridge

Chukar partridges were fed diets containing 1.25, 2.5, or 5 ppm aflatoxin; 1, 2, or 4 ppm ochratoxin A (OA); or 4, 8, or 16 ppm T-2 toxin. Toxin-induced mortality was seen during the third week with 4 ppm OA (12.5%) and 16 ppm T-2 toxin (15%), compared with the mortality in control chukars fed no toxin (2.5%). Body weights were significantly decreased by the highest level of aflatoxin at 3 weeks of age, by the highest level of OA by 2 weeks of age, and by 8 and 16 ppm T-2 toxin by 1 week of age. Aflatoxin did not affect liver weight and OA did not increase kidney weight in 3-week-old chukars. There was a slight decrease in kidney weight in chukars fed 4 ppm OA; however, the decrease was related to the decrease in body weight produced by the toxin. Mouth lesions were seen at all levels of T-2 toxin fed.     

Effects of sarcoptic mange on lactating swine and growing pigs

The impact of Sarcoptic mange on sows and on performance of their offspring from birth to slaughter was determined. Sows naturally infested with Sarcoptic mange were paired, mated to the same boar, and assigned randomly to treated or control farrowing groups. Treated sows received ivermectin s.c. at 300 micrograms/kg body weight; control sows received the vehicle s.c. Sow performance was evaluated via sow feed consumption, litter size, litter birth weights, litter weaning weights and piglet death loss from birth to weaning. Seven replicates (farrowing groups), each with six sow pairs, were included in the trial. Offspring from treated and control sows, 35 head/group, were fed to slaughter weights. Untreated sows had litters that weighed 4.14 kg less than ivermectin-treated sow litters at 21 d (P less than .07). Treated sows consumed 1.95 kg less feed per weaned piglet and .13 kg less feed per kilogram of weaned piglet (P less than .05). Piglets from treated sows were 5.79 kg/head heavier at slaughter (P less than .05) and had a .05 kg/d superior average daily gain (P less than .05).     

Characterization of the toxicity of the mycotoxins aflatoxin, ochratoxin, and T-2 toxin in game birds. II. Ringneck pheasant.

Ringneck pheasants were fed diets containing 1.25, 2.5, or 5 ppm aflatoxin; 1, 2, or 4 ppm ochratoxin A (OA); or 4, 8, or 16 ppm T-2 toxin. Severe toxin-induced mortality was seen during the first to third weeks with 2.50 and 5.00 ppm aflatoxin (92.5% and 97.5%, respectively), compared with the mortality in control pheasants fed no toxin (0%). Slight mortality (less than or equal to 5%) was seen with OA and T-2 toxin. Body weights were significantly decreased by the lowest level (1.25 ppm) of aflatoxin by 2 weeks of age, by the two highest levels of aflatoxin by 1 week of age, and by 16 ppm T-2 toxin by 1 week of age. The feed-conversion ratio was increased by 2.50 and 5.00 ppm aflatoxin compared with the feed-conversion ratio in controls, although high mortality may have influenced the results. Aflatoxin had no effect on liver weight, but OA increased kidney weight in 3-week-old pheasants. Mouth lesions were seen in some of the pheasants fed T-2 toxin.     

Effects of aflatoxin on the growth performance and immune responses of weanling swine

Aflatoxin (AF)-contaminated ground corn was mixed with a commercial swine ration to yield 2 concentrations (500 mg of AFB1/kg of feed [A] and 300 mg of AFB1/kg [B]) and was fed to 2 groups of pigs. Groups A and B were fed the AF-containing ration, whereas control group C was fed the same commercial ration mixed with ground corn devoid of AF. A comparative analysis of the average weight gain per pig in each of the treatment groups, compared with that in the control group, indicated a significantly (P less than 0.01) greater weight gain in the control group. The average feed conversion rate was also significantly (P less than 0.01) lower in group A pigs, compared with that in the control group. The humoral immune response to Erysipelothrix rhusiopathiae, measured by enzyme-linked immunosorbent assay, did not reveal a significant difference among groups; there were no consistent differences observed in the proliferative responses of lymphocytes to mitogens. In contrast, a significant (P less than 0.05) reduction in complement titers was observed, whereas an increase in serum immunoglobulin G and M values occurred in the AF-treated group A, compared with that in group C. Gross enlargement of the liver, substantiated by histologic evidence of toxic damage to the hepatic parenchyma, revealed that AF at concentrations of 500 mg/kg of feed was toxigenic and produced an adverse effect on the growth rate, feed efficiency, and general well-being of young pigs.     

Effects of aflatoxin on the development of acquired immunity to swine erysipelas

The effect of aflatoxin consumption on the development of acquired immunity to swine erysipelas was studied. Twenty-four pigs were divided into 4 groups (6 pigs/group). Two groups were fed a normal diet and 2 groups were fed the same diet but containing aflatoxin. One group from each diet treatment was given a single injection of an erysipelas bacterin, and 21 days later all pigs were given a challenge inoculum of virulent Erysipelothrix rhusiopathiae organisms. On the basis of the response to the challenge inoculation, pigs were classified as immune, partially immune (PI), or susceptible. Three of the vaccinated pigs fed the normal diet were immune, 2 were PI, and 1 was susceptible, whereas none of the vaccinated pigs given the aflatoxin diet were immune, only 1 was PI, and the remainder were susceptible. Two of the nonvaccinated pigs fed the normal diet were PI and 4 were susceptible; all of the nonvaccinated pigs fed the aflatoxin diet were susceptible. It was concluded that aflatoxin consumption interfered with the development of acquired immunity and apparently increased the severity of the E rhusiopathiae infection in unvaccinated pigs.     

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.     

Characterization of the toxicity of the mycotoxins aflatoxin, ochratoxin, and T-2 toxin in game birds. III. Bobwhite and Japanese quail.

Bobwhite and Japanese quail were fed diets containing 1.25, 2.50, or 5.00 ppm aflatoxin; 1, 2, or 4 ppm ochratoxin A (OA); or 4, 8, or 16 ppm T-2 toxin. Aflatoxin induced mortality in bobwhites during the second and third week with 1.25 ppm (10%), 2.50 ppm (30%), and 5.00 ppm (40%), and during the same period with T-2 toxin at 8 ppm (20%) and 16 ppm (22.5%). Body weights of bobwhite quail were significantly decreased by the two higher levels of aflatoxin by 2 weeks of age, and by the two higher levels of T-2 toxin by 1 week of age. In Japanese quail, only the highest level of aflatoxin and T-2 toxin reduced body weight (by 3 weeks and by 1 week of age, respectively), and even then to a much lesser extent than in bobwhites (less than 10%). Aflatoxin did not affect feed-conversion ratio (FCR) in bobwhite quail, but the two higher levels of T-2 toxin increased FCR. None of the toxins induced mortality or increased the FCR in Japanese quail. Aflatoxin increased liver weight in both bobwhite and Japanese quail. OA increased kidney weight in 3-week-old Japanese quail but had no effect on the kidney weight of bobwhite quail. Mouth lesions were progressively more severe in bobwhite quail fed increasing levels of T-2 toxin, but lesions were far less severe in Japanese quail.     

Cocontamination of swine diets by aflatoxin and diacetoxyscirpenol

The effects of dietary aflatoxin (AF) and diacetoxyscirpenol (DAS), singly and in combination, were evaluated in growing crossbred barrows. The experimental design consisted of 4 treatments of 9 barrows each fed diets containing 1) 0 mg AF and 0 mg DAS/kg feed (control), 2) 2.5 mg AF/kg feed, 3) 2.0 mg DAS/kg feed, or 4) 2.5 mg AF + 2.0 mg DAS/kg feed for 28 days (10-14 weeks of age). Production performance, serum biochemical, hematologic, and pathologic measurements were made. Body weight and body weight gain were significantly decreased by each toxin but more so by the combination treatment. The effects were additive in nature. Liver and spleen weights, as percentages of body weight, were increased by the AF and AF + DAS treatments, and AF or AF + DAS treatments induced diffuse hepatocellular vacuolar change, early portal fibrosis, and early bile duct hyperplasia. Aflatoxin increased serum values of creatinine and gamma glutamyl transferase, cholinesterase, and alkaline phosphatase activities; increased packed cell volume and hemoglobin; and decreased urea nitrogen and total iron binding capacity. DAS reduced serum iron binding capacity. The AF + DAS treatment increased serum gamma glutamyl transferase and alkaline phosphatase activities, increased hemoglobin, and decreased serum iron binding capacity. Generally, the combination treatment could be described as additive or less than additive, with most of the effects attributable to AF. Under the conditions and parameters monitored in this study, AF and DAS had no synergistic toxic effects when incorporated into diets of growing barrows.     

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。     

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.