Occurrence of Fusarium strains and their mycotoxins on corn silage. 6. Formation of zearalenone and trichothecenes (type A) by indigenous Fusarium isolates

A total of 399 indigenous Fusarium strains mainly isolated from silage maize were tested for the production of zearalenone and type A trichothecenes by thin-layer chromatography and biological assays. About 45% of the isolates examined were capable of producing different levels of zearalenone and trichothecene toxins on a cracked corn substrate. The majority of these strains (75%) produced zearalenone only and no trichothecenes type A. The results of the biological tests indicated a higher rate of toxin-positive extracts than chemical analysis. Isolates of nine out of seventeen Fusarium species examined produced one or several mycotoxins looked for. The most important toxin producers were F. culmorum and F. crookwellense (zearalenone) and F. sporotrichioides (trichothecenes type A), respectively. F. avenaceum, the species most frequently isolated from silage maize, produced neither zearalenone nor trichothecenes but avenacein Y a antibiotic compound. First results of a study of the production of type B trichothecenes have shown that indigenous F. culmorum isolates were capable of producing high levels of deoxynivalenol.     

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.     

Relationships of Fusarium toxins to tumours and other disorders in livestock

Experimental laboratory animals treated with the trichothecene T-2 toxin, develop various acute and chronic disorders and also tumours of the digestive tract and of the brain. T-2 toxin is teratogenic and immunosuppressive. In livestock, ingestion of fodder contaminated with T-2 toxin and with certain other trichothecenes can cause various disorders, including a haemorrhagic syndrome, neurological and reproductive disturbances. Follow-up studies of survivors in the flocks or herds which suffered fatalities from acute mycotoxicoses could establish whether and which chronic disorders and tumours may develop among the survivors and among their progeny, as a result of exposure to mycotoxins, which caused the acute fatalities. Outbreaks of acute mycotoxicoses are usually preceded by exceptional weather.     

Investigation on trichothecene-stimulated lipid peroxidation and toxic effects of trichothecenes in animals

Three experiments were performed with mice intoxicated with trichothecene-contamined feed or directly into the stomach. Lipid peroxidation was estimated by the TBA value from liver samples, but since such a test seldom provided reliable results, lipid hydroperoxides and total carbonyl were also analyzed. The formation of aldehydes and ketones was compared in vivo and in vitro. The same investigations were conducted on chickens, rainbow trouts and numerous fur animals suspected of chronic intoxication by trichothecenes. The vitamin A concentration was used as a parameter to detect alterations caused in chickens by trichothecenes. Our investigation provided evidence that lipid peroxidation is associated with trichothecene poisoning. The T-2 toxin, even in small concentrations, seems to induce strong lipid peroxidation. When DON and 3-AcDON were given together at a dosage of 180 micrograms/kg feed, 1 week's feeding caused clear lipid peroxidation in mice. Particular attention should be paid to the fact that mycotoxins may already be present in the feed before any experiment is conducted.     

Sickness behavior, its mechanisms and significance

Recent studies have begun to clarify the pathogenesis of sickness behavior. Cytokines released by macrophages, dendritic cells and mast cells act on the brain to trigger behavioral changes in infected animals. The major cytokines, interleukin-1, tumor necrosis factor alpha, and others, all act on the hypothalamus to provoke alterations in the normal homeostatic condition. These include elevated body temperature, increased sleep, and loss of appetite as well as major alterations in lipid and protein metabolism leading to significant weight loss. Some of these changes are clearly directed towards enhancing the normal immune responses. The benefits of others such as appetite loss are unclear. It is also important to recognize that other animals may recognize sickness behavior as a sign of weakness and mark the victim out for targeting by predators. As a result, some prey species may work very hard to mask their sickness, a response that serves to complicate veterinary diagnosis.     

脱氧雪腐镰刀菌烯醇导致厌食和呕吐的机制研究进展

由镰刀菌产生的脱氧雪腐镰刀菌烯醇(DON)广泛存在于谷物及其加工产品中,对动物和人类健康有着潜在的危害。DON具有多方面的毒性作用,而厌食和呕吐是机体摄入DON后出现的最典型症状,厌食和呕吐的产生主要归因于DON对中枢神经系统和胃肠道食欲因子的影响。DON可直接作用于中枢神经系统的呕吐中枢产生呕吐反射,同时激活下丘脑神经元分泌食欲调节因子影响采食;DON可诱导肠内分泌细胞分泌肽YY、胆囊收缩素等食欲调节因子从而引发厌食;DON对中枢神经系统和胃肠道分泌的影响又可通过肠-脑轴产生关联;此外,细胞因子及肠道微生物也部分参与了反应的介导。本文综述了DON诱发机体出现厌食和呕吐的可能机制,以期为找到相应解决措施提供理论指导。     

镰刀菌毒素对动物毒性作用的研究进展

镰刀菌是污染粮食和饲料的主要真菌菌属之一,可产生多种高毒性、低分子量的代谢产物,如玉米赤霉烯酮、脱氧雪腐镰刀菌烯醇、T-2毒素等,这些毒素严重威胁动物和人类的健康。摄入镰刀菌毒素可对动物造成多种毒性作用,包括生殖毒性、免疫毒性、肠道毒性、肝肾毒性、细胞毒性及致癌性等。不同类型镰刀菌毒素引起的毒性作用不尽一致,且不同毒素间存在互作效应。为此,本文对单一或混合镰刀菌毒素毒性的研究进展进行了总结和归纳,为镰刀菌毒素的深入研究提供参考和借鉴。     

Zearalenone--undesirable substances in feed

The main arguments, discussed by different international organizations, which confirm the significance of problems connected with the presence of zearalenone in animal feed materials and their influence on the safety of food materials are shown in this review article. The main world research trends focused on zearalenone, as undesirable substances, are also presented. A variety of Fusarium fungi produce a number of different mycotoxins, for example zearalenone. Is not true that Fusarium fungi are they the most prevalent toxin-producing fungi only in the northern temperate regions, are also commonly found on cereals grown in the temperate regions of America, Europe and Asia. Zearalenone have been shown to cause a variety of toxic effects in both experimental animals and livestock, and have also been suspected of causing toxicity in humans. Zearalenone is a stable compound, both during storage/milling and the processing/cooking of food, and it does not degrade at high temperatures. Studies of metabolism indicate that zearalenone is fairly rapidly absorbed following oral administration, with the formation of alpha- and beta-zearalenol and alpha- and alpha-zearalanol, which are subsequently conjugated with glucuronic acid. This mycotoxin and some of these metabolites have been shown to competitively bind to estrogen receptors in a number of in vitro systems. Binding to specific receptors has been demonstrated in the uterus, mammary gland, liver and hypothalamus of different species. Additionaly alterations of immunological parameters were found at high zearalenone concentrations in vitro. Zearalenone causes alterations in the reproductive tract of laboratory animals and domestic animals. Various estrogenic effects such as decreased fertility, increased embryolethal resorptions, reduced litter size, changed weight of adrenal, thyroid and pituitary glands and change in serum levels of progesterone and estradiol have been observed, and teratogenic effects were found in pigs and sheep. It may be that the safety of zearalenone could be evaluated on the basis of the dose which had no hormonal effects in pigs, the most sensitive species, and a temporary Tolerable Daily Intake for zearalenone of 0.2 microgram/kg of body weight, could be established.     

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.     

Fusarial toxins and their role in animal diseases

Fusarial toxins are toxic metabolites produced mostly by toxigenic micromycetes of genus Fusarium. Dominant mycotoxins of this group include trichothecenes, moniliformin, zearalenone, and fumonisins. Recently, special attention has been paid to these toxins because of their harmful effects on both animals and humans. On the basis of the available literature, we review here the characteristics of major fusarial mycotoxins with an emphasis on their toxic effects on animals. The most important fusarial mycotoxins, their sources, and their pathology including clinical signs, necropsy findings, as well as changes in haematological, biochemical, and immunological indices, are addressed.     

Effect of fusaric acid on brain regional neurochemistry and vomiting behavior in swine.

Fusaric (5-butylpicolinic) acid is a phytotoxin produced especially by Fusarium moniliforme, a mold commonly found in Canadian-grown corn. Experiments were conducted to determine the effects of acute doses of fusaric acid on brain neurochemistry and behavior in swine. A total of 40 crossbred barrows (initial weight 10 kg) were orally dosed with 0 or 200 mg of fusaric acid/kg of BW and five animals from each treatment were killed 4.5, 9, 18, or 36 h after dosing. All brains were dissected, and concentrations of indoleamine and catecholamine neurotransmitters and metabolites were determined. Animals in the group killed 36 h after dosing were observed for behavioral changes. Vomiting was noted in 60% of the pigs dosed with fusaric acid. These pigs also seemed more lethargic than controls and appeared sedated. The major neurochemical changes due to exposure to fusaric acid were seen in the hypothalamus 18 h after dosing. Brain tryptophan, serotonin, and 5-hydroxyindoleacetic acid all tended to be elevated by the action of fusaric acid. Brain catecholamine concentrations were largely refractory to treatment. It was concluded that exposure to acute doses of fusaric acid can cause vomiting and neurochemical changes in swine. Fusaric acid may, therefore, be acting synergistically with trichothecene mycotoxins to cause vomiting and feed refusal in pigs consuming trichothecene-contaminated feedstuffs.     

Melanocortin-4 receptor in sheep: a potential site for therapeutic intervention in disease models

Reduced appetite combined with increased metabolic rate and decreased lean body mass is a major consequence of disease and other stressors. Studies in rodent species suggest that an understanding of appetite regulation may provide methodologies for intervention to prevent the deterioration of body mass such as observed with cancer or infectious diseases. For example, melanocortin-4 receptor (MC4-R) antagonists have shown a remarkable ability to reverse or prevent cachexia in rodents with sarcoma or treated with endotoxin. Studies in sheep have indicated that a number of peptide neurotransmitters may have a role in regulating appetite in this species. For example, agouti related protein mRNA and protein levels are dramatically altered with fasting in sheep. Moreover, agouti related protein, neuropeptide Y, melanin concentrating hormone and orexin are potent stimuli to increase feed intake in sheep. Recent studies have indicated that one of these neurotransmitters, NPY, can work in principal to improve appetite in endotoxin-treated sheep. Current studies are examining the role that MC4-R antagonists may have in the prevention or correction of body mass wasting diseases as well as practical applications in animal production.     

Chronic,including teratogenic and carcinogenic effects of trichothecenes: A short review

Trichothecenes are toxic sesquiterpenes, produced as secondary metabolites by certain soil microfungi in agricultural products harvested during wet and cold weather, and/or stored inappropriately. When present in the ingested food they can cause haemorrhagic diathesis, acute and chronic disorders in many animal species, including man. Animals experimentally treated with T-2 toxin, one of the common, very toxic and immunosuppressive trichothecenes, develop gastrointestinal, skin, and neurological disorders. T-2 toxin given to pregnant animals can lead to abortion and fetal abnormalities. Rats surviving many months after several sublethal doses of T-2 toxin can develop cardiovascular lesions, high blood pressure and tumours, benign and malignant, of the brain, the pancreas, stomach, and certain other organs. The possibility has to be considered that trichothecenes may be involved in some similar idiopathic disorders and tumours in livestock and in man.     

Management of anorexia in the cat.

One of the most frequent motivations for seeking veterinary attention for a cat is when the owner recognises a loss of normal appetite in his pet. The medical term for a lack of appetite for food is 'anorexia', and it may be partial or complete. While anorexia is a common manifestation of disease, the mechanisms underlying decreased food intake are complex and not completely understood. The regulation of appetite involves interaction of external stimuli with signals from the gastrointestinal tract and central nervous system. Aberrations in any of the internal control systems for hunger and satiety, or changes in external factors such as diet or feeding environment, can result in partial or total anorexia. The challenge for the practitioner is not only to diagnose and treat the underlying condition, but to recognise at what point inadequate food intake has or will impinge on the patient's nutritional status to the extent that it might deleteriously affect clinical outcome. It is also important to bear in mind the significance that the patient's appetite and food intake has for the cat owner in his overall perception of his pet's condition and quality of life.     

Experimental ochratoxicosis A in pigs

SUMMARY Ochratoxin A was isolated from a culture of Aspergillus ochraceus grown on a cornmeal substrate. The mycotoxin was added to a grower ration for 14 kg young pigs at 2, 4, 8 and 16 mg/kg and fed to groups of 3 for periods ranging from 6 to 20 days. The highest dose rate group only became sick, with loss of appetite, weight loss, polydipsia, polyuria, proteinuria, glucosuria, elevation of serum creatinine, pale swollen kidneys, renal tubular degeneration and cortical fibrosis. The pigs on the 2 mg toxin/kg of diet appeared unaffected with only slight renal tubular degeneration present in one animal. Feeding diet contaminated with the intermediate doses of 4 and 8 mg toxin/kg diet lead to reduction of weight gain and/or reduced feed intake and feed conversion efficiency as well as mild renal lesions. Ochratoxin A has recently been reported on mould-affected grain in Queensland and some local strains of A. ochraceus in culture have been shown to be able to produce levels of ochratoxin A of up to 4000 mg/kg of substrate. Rare episodes of nephrotoxicity in pigs seen at slaughter in Queensland may thus be due to prior contamination of the diet with ochratoxin A.     

Mycotoxins in fungal contaminated samples of animal feed from western Canada, 1982-1994.

Feed samples from 94 cases involving fungal contamination and suspected mycotoxicosis of farm animals in western Canada were examined during 1982-1994 to assess the incidence of mycotoxins. Samples were analyzed for aflatoxins, ochratoxin A, citrinin, sterigmatocystin, and the fungal estrogen zearalenone. Samples infected with Fusarium fungi were additionally assayed for nivalenol, deoxynivalenol, fusarenone-x, 15-acetyl-deoxynivalenol, diacetoxyscirpenol, HT-2 toxin, and T-2 toxin. Mycotoxins were found in 21 feed samples from 17 cases (18% of the reported cases), generally at levels far below those needed to induce symptoms under laboratory conditions. HT-2 toxin and other type-A trichothecenes were detected in 5 samples, deoxynivalenol and other type-B trichothecenes in 13, ochratoxin A in 5, and citrinin in 2. In 9 cases, symptoms observed in the animals were consistent with the known effects of the mycotoxin(s) found in the particular feed samples.     

植物病原镰刀菌产生的毒素种类及其危害

镰刀菌(Fusarium spp.)是多种重要农作物的病原体，不仅可造成农作物产量和品质的严重损失还可在离体培养条件下或植物寄主体内产生一系列被称为镰刀菌毒素的次生代谢产物。这些毒素一方面作为致病因子与镰刀菌对宿主植物的致病力密切相关，另一方面可导致家畜生产性能下降和相关病症的出现，进而影响农业生态系统并对人类健康造成威胁。鉴于镰刀菌毒素对农作物生产的影响及其对家畜和人类的毒性作用，目前已有较多关于镰刀菌侵染粮食作物后产生毒素种类的研究，但关于镰刀菌侵染豆科牧草后产生的毒素种类以及毒素在镰刀菌对豆科牧草致病力方面作用的研究则较少。本文对引起主要粮食和饲料作物病害的常见镰刀菌物种产生的主要毒素，以及这些毒素对植物、家畜和人类的危害进行了综述，并对豆科牧草中镰刀菌毒素的研究前景及意义进行了展望。     

Effect of acute oral doses of T-2 toxin on tissue concentrations of biogenic amines in the rat

T-2 toxin [3 alpha-hydroxy-4 beta, 15-diacetoxy-8 alpha-(3-methylbutyryloxy)-12,13-epoxytrichotec-9-ene] is an emetic Fusarium trichothecene mycotoxin known to cause lethargy, ataxia and feed refusal in economically important animals. Experiments were conducted to determine the effect of acute oral doses of T-2 toxin on tissue concentrations of neurotransmitters thought to play some role in regulation of feed consumption. Sixty-seven male weanling rats were intubated with a few grams of diet in a liquid slurry with or without 2.0 mg T-2 toxin per kilogram of body weight. At 1, 2, 4, 6, 8, 12, 24 and 48 h following dosing, rats were killed, and brains, spleens, hearts and adrenal glands were excised and analyzed for concentrations of neurotransmitters and metabolites using high-performance liquid chromatography with electrochemical detection. Administration of T-2 toxin caused increases in brain concentrations of tryptophan and serotonin at the early time intervals after dosing. Brain concentrations of dopamine increased, whereas concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) decreased at the later time interals following dosing. Concentrations of dopamine were increased in adrenal glands, whereas epinephrine concentrations decreased. Epinephrine was detected in spleen and heart after administration of T-2 toxin. It was concluded that the increase in brain indoleamines induced by T-2 toxin could contribute to feed refusal in animals suffering from T-2 toxicosis.     

Laboratory evaluation of malassimilation in horses

Malassimilation should be suspected in horses with weight loss in spite of a good appetite. Malassimilation is usually confirmed with oral glucose or D-xylose absorption tests, whereas the oral lactose tolerance test can be used to evaluate lactase deficiency in foals. Once malassimilation is confirmed, other diagnostic tests such as abdominocentesis, rectal mucosal biopsy, or exploratory laparotomy with intestinal biopsies may determine the etiology of malassimilation.