fumonisin-b1 and Weight-Gain

Twenty-four male weaned piglets assigned to four diets containing 5.0, 10.0, 15.0 and 0.2 mg fumonisin B(1) (FB(1)) /kg as diets 1, 2, 3 and control diet, respectively, were used to study the effect of dietary FB(1) on growth and puberty attainment in pigs in a 6-month feeding trial. Lower feed intake during 0-4 months and a non-significant (p > 0.05) but FB(1) concentration-dependent decrease in live and DWGs in animals fed FB(1)-contaminated diets was observed at the end of the pubertal phase. The daily and the final live weight gains of animals fed diet 3 were 75.8% and 90.6%, respectively, of the control values. The mean ages at puberty by boars on diets 2 and 3 were significantly (p < 0.05) higher than those for animals on the control and diet 1. The animals on diet 3 attained puberty when mean live weight was 60.1 kg, some 30.3 days after the controls attained puberty, at 156.3 days, when the mean live weight was 46.9 kg. This study revealed that dietary FB(1) delays sexual maturity in growing pigs. Male weanling pigs for breeding should not be exposed to dietary FB(1) higher than 5 mg/kg for optimum growth and reproductive performance.

Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Diet; Fumonisins; Male; Sexual Maturation; Swine; Weight Gain

The nature of cancer initiation by fumonisin B(1) (FB(1)) was investigated in rat liver by monitoring the effect of phenobarbital (PB) as cancer promoter and evaluating the involvement of spontaneously initiated cells. A PB promoting regimen (0.05% in the diet) stimulated the outgrowth of FB(1)-induced placental glutathione S-transferase (GSTP) positive initiated hepatocytes. Reversion of the FB(1)-induced GSTP(+) foci was noticed in the absence of a promoting regimen. Younger rats were shown to be more sensitive to the induction of GSTP(+) foci by FB(1). Cancer initiation by FB(1) was associated with a hepatotoxic effect, which was less pronounced in older rats presumably due to a reduced intake. A specific role of spontaneously initiated cells and their promotion by FB(1) into the development of eosinophilic clear cell foci could not be established under the present experimental conditions. The ability of different stimuli to selectively promote the outgrowth of FB(1) initiated cells further verifies the cancer initiating potency of this apparent non-genotoxic mycotoxin. The underlying mechanism(s) involved in the genesis of the initiated hepatocytes is not known at present.

Topics: Animals; Body Weight; Carcinogenicity Tests; Carcinogens; Diet; Enzyme Induction; Fumonisins; Glutathione S-Transferase pi; Glutathione Transferase; Hepatocytes; Liver Neoplasms, Experimental; Male; Phenobarbital; Rats; Rats, Inbred F344; Weight Gain

Fumonisin (FB1), a mycotoxin, is produced by Fusarium moniliforme and F. proliferatum. A prevalence survey in Taiwan by our laboratory showed that there was a contamination rate of 40% in domestic animal feeds, and the average contaminated level was 4.5 mg/kg. Ninety-six birds were allotted into four treatments fed with diets containing 0 (control), 5, 10, or 15 mg/kg of FB1 for three weeks. The results showed that the growth performance was not influenced by the FB1 challenge, but relative bursa weight was significantly decreased. The activity of serum aspartate aminotransferase, and the serum levels of albumin and cholesterol were significantly elevated by the FB1 challenges. When broilers were stimulated with injection of lipopolysaccharides, mRNA abundance (determined by semi-quantitative RT-PCR) interleukin-1beta (IL-1beta), IL-2, interferon-alpha (IFN-alpha), IFN-gamma, and inducible nitric oxide synthase (iNOS) reached a plateau at 3 h, and declined at 6 h. A FB1 challenge for three weeks increased cytokine mRNA abundance in broilers. The results also showed that 15 mg FB1 per kg feed significantly inhibited the expression of IL-1beta, IL-2, IFN-alpha, IFN-gamma, but had no effect on iNOS. The macrophage functional profile was significantly changed under an exposure of 15 mg FB1 per kg for three weeks. Taken together, our results suggest that FB1 up to 15 mg/kg does not affect growth performance, but impairs some parameters of blood biochemistry and the immunocompetence in broilers.

Topics: Animal Feed; Animals; Bursa of Fabricius; Carcinogens, Environmental; Chickens; Cytokines; Dose-Response Relationship, Drug; Food Contamination; Fumonisins; Gene Expression Regulation; Immunocompetence; Macrophages; Organ Size; Random Allocation; Weight Gain

The effects of fumonisin B-glucose reaction products in swine diets was examined. Pigs were fed diets containing 528 micromol of total fumonisin B/kg (FB), 528 micromol of total FB-glucose adducts/kg (FB-G, 122 micromol of unreacted FB/kg), or 0 micromol of total FB/kg for 15 days to test the efficacy of the FB-G reaction products in detoxifying FB. Weight gain in FB pigs was lower than in FB-G or controls, which was correlated with feed intake reduction in FB pigs. Serum aspartate aminotransferase, gamma-glutamyltransferase, and total bilirubin in FB pigs were higher than in FB-G or control pigs. Serum sphinganine/shingosine ratios in FB pigs were higher than in FB-G or control pigs. Microscopic examination of tissues from FB pigs showed generalized liver necrosis and apoptosis with marked cellular pleomorphism and disorganized hepatic cords. The liver and kidneys in the FB-G group appeared to be normal. Tissues of controls were free of lesions. Results suggest that dietary FB-G products are less toxic to swine and may provide an detoxification approach in instances of widespread FB grain contamination (p < 0.05).

Topics: Animal Feed; Animals; Apoptosis; Aspartate Aminotransferases; Bilirubin; Diet; Fumonisins; gamma-Glutamyltransferase; Glucose; Liver; Necrosis; Swine; Weight Gain

The aim of the study was to evaluate the effect on broiler performance of transgenic Bacillus thuringiensis (Bt) corn containing the Cry1A(b) protein compared with the corresponding near isogenic corn and to analyze the degradation of the Cry1A(b) gene in the digestive tract. Ross male broilers (432) were fed for 42 consecutive days with diets containing Bt or isogenic corn. Diet, Bt corn, and the isogenic form of the Bt corn were analyzed for composition and aflatoxin B1, fumonisin B1, and deoxynivalenol contents. Broiler body weight and feed intake were recorded at regular intervals (d 0, 21, and 42). The presence of the Cry1A(b) gene and plant-specific genes Zein and Sh-2 in gut contents of crop, gizzard, jejunum, cecum, and samples of blood was determined in 10 animals per treatment at the end of the trial using a PCR technique. Chemical composition was not different between Bt and its isogenic form, whereas the fumonisin B1 content for Bt was lower than for isogenic corn (2,039 vs. 1,1034 ppb; P < 0.05). The results of the growth study showed no difference for average daily weight gain (129.4 vs. 126.0 g/d), feed intake (63.4 vs. 61.8 g/d), and feed conversion ratio (1.95 vs. 2.02) among the groups. No significant relationship was observed between mycotoxins content and growth performances. Feed-derived DNA is progressively degraded along the digestive tract. Detection frequency of short fragments of maize-specific high copy number Zein gene was high but significantly decreased in distal sectors. An 1,800-bp fragment of the Cry1A(b) gene, corresponding to the minimal functional unit, was detected only in crop and gizzard of birds fed Bt corn. Sh-2 showed the same detection frequency of Cry1A(b) and was also found in birds fed isogenic corn. Blood samples were positive with low frequency only for the Zein gene fragment. No significant difference in DNA detection was observed between birds fed Bt and isogenic corn, indicating that DNA derived from transgenic feed undergoes the same fate as isogenic feed.

Topics: Aflatoxin B1; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Bacillus thuringiensis Toxins; Bacterial Proteins; Bacterial Toxins; Chickens; DNA, Bacterial; DNA, Plant; Eating; Endotoxins; Fumonisins; Hemolysin Proteins; Intestines; Plants, Genetically Modified; Trichothecenes; Weight Gain; Zea mays; Zein

The effects of fumonisin B1 (FB1) from Fasarium verticillioides culture material and moniliformin from Fusarum fujikuroi culture material on growing barrows were evaluated. Four groups of six barrows (three replicates of two each; mean body weight, 11.1 kg) were fed diets containing 0 mg of FB1 and 0 mg of moniliformin per kg of feed (control), 100 mg of FB1 per kg of feed, 100 mg of moniliformin per kg of feed, and 100 mg of FB1 plus 100 mg of moniliformin per kg of feed. Barrows were fed these diets for 28 days. Body weight gain, feed efficiency, serum biochemical analytes, and hematological values were adversely affected by the FB1 and the FB1-plus-moniliformin diets. The moniliformin diet decreased body weight gain. Two barrows in the moniliformin diet group died, and two barrows in the FB1-plus-moniliformin diet group died. All deaths occurred during the first 6 days of the study. Mild to moderate lesions were observed microscopically in heart and lung tissues of the groups fed moniliformin and FB1 plus moniliformin and in liver tissues of the groups fed FB1 and FB1 plus moniliformin. Except for the acute mortality associated with the two diets containing moniliformin. clinical disease induced by the combined feeding of these two mycotoxins appears to be additive or less than additive and due primarily to the toxic expression of FB1.

Topics: Animal Feed; Animals; Carboxylic Acids; Cyclobutanes; Energy Intake; Food Contamination; Food Microbiology; Fumonisins; Fusarium; Liver; Lung; Male; Myocardium; Swine; Weight Gain

Effects of feeding diets containing fumonisin B1 (FB1) and moniliformin (M), singly or in combination, on performance and immune response were evaluated in poults. Day-old poults were randomly assigned to one of four dietary treatments with four replicates of four poults each. Dietary treatments were 1) control; 2) 200 mg FB1, 0 mg M/kg diet; 3) 0 mg FB1, 100 mg M/kg diet; and 4) 200 mg FB1, 100 mg M/kg diet. In Experiment 1, poults were injected with 0.25 mL Newcastle disease virus (NDV) vaccine on Weeks 2 and 3 of the experiment, and anti-NDV antibody titers were measured 7 d after each injection. Compared with controls, poults fed FB1 had significantly lower (P < 0.05) secondary antibody response. Poults fed M and the combination of FB1 and M had significantly lower (P < 0.05) primary and secondary antibody response. Lower relative thymus weights were observed in poults fed diets containing FB1 or M. Decreased relative bursa and spleen weights were observed in poults fed M. In Experiment 2, poults were placed on dietary treatments for 3 wk. On Day 21, 2 x 10(6) peripheral lymphocytes were incubated with mitogens. Poults fed diets containing FB1 had a significantly lower (P < 0.05) proliferative response to mitogens in comparison to controls. In Experiment 3, poults were placed on the diets for 3 wk and were injected with 4.4 x 10(7) E. coli/kg body weight on Day 21. Significantly higher (P < 0.05) numbers of E. coli colonies were observed in the blood and tissue homogenates of poults fed M. In all three experiments, feed intake and body weight gains were significantly lower (P < 0.05) in turkeys fed diets containing M. Data from the present study suggest that FB1 and M are immunosuppressive in poults and that M not only suppresses immune response but also performance. However, neither synergistic nor additive effects between FB1 and M were observed for any of the parameters measured.

Topics: Animals; Antibodies, Viral; Carboxylic Acids; Cyclobutanes; Diet; Eating; Escherichia coli; Escherichia coli Infections; Female; Fumonisins; Immunity; Immunosuppressive Agents; Lymphocyte Activation; Newcastle disease virus; Turkeys; Viral Vaccines; Weight Gain

The present study was performed to determine whether excess hepatic iron modulates the cancer-initiating and promoting properties of FB1. Thirty-eight male F344 rats were divided into four dietary treatment groups: (i) control diet (AIN, n = 8); (ii) FB1 250 mg/kg diet (FB1, n = 10); (iii) 1-2% carbonyl iron (CI, n = 10); or (iv) FB1 plus iron loading (FB1/CI, n = 10) for 5 weeks (2 x 2 factorial design). Hepatic iron concentrations in iron-loaded animals at 5 weeks were 444 +/- 56 (CI) and 479 +/- 80 micromol/g dry weight (FB1/CI) (mean +/- SEM). All the FB1-fed rats, in the presence or absence of CI, developed a toxic hepatitis with a 4-fold rise in serum alanine transaminase (ALT) levels. FB1 appeared to augment iron-induced hepatic lipid peroxidation, as measured by the generation of thiobarbituric acid reacting substances (TBARS) in liver homogenates (P < 0.0001). Morphometric analysis showed that FB1 caused a significantly greater mean +/- SEM number of 'enzyme-altered' foci and nodules per cm2 (5.34 +/- 1.42 vs. 1.50 +/- 0.52, P < 0.05), as well as a greater area (%) of liver occupied by foci and nodules (0.33 +/- 0.12% vs. 0.05 +/- 0.03%, P < 0.001), compared with FB1/CI. The addition of FB1 to dietary iron loading caused a shift in distribution of iron from hepatocytes to Kupffer cells, probably due to phagocytosis of necrotic iron-loaded hepatocytes. In conclusion, (i) FB1 appears to cause toxicity in the liver independently from effects on lipid peroxidation; (ii) FB1 has a potentiating effect on iron-induced lipid peroxidation; and (iii) dietary iron loading appears to protect against the cancer promoting properties of FB1, possibly due to a stimulatory effect of iron on hepatocyte regeneration.

Topics: Animals; Carboxylic Acids; Carcinogens, Environmental; Fumonisins; Glutathione S-Transferase pi; Glutathione Transferase; Iron Overload; Isoenzymes; Lipid Peroxidation; Liver; Liver Neoplasms, Experimental; Male; Organ Size; Rats; Rats, Inbred F344; Weight Gain

Fumonisins are mycotoxins produced by Fusarium moniliforme, F. proliferatum, and related Fusarium species found on corn. They occur naturally in corn-based feeds and foods and are suspected human esophageal carcinogens. Fumonisin B1 (FB1), the most common homologue, causes the animal diseases associated with F. moniliforme. Hepato- and nephrotoxicities, disrupted sphingolipid metabolism, and liver cancer have been found in rats fed FB1. To determine the in vivo effects of diets containing fumonisins B2 (FB2) or B3 or (FB3), male rats were fed culture materials (CM) of FB1 non-producing F. moniliforme isolates to provide low (4.6-6.7 ppm), mid (32-49 ppm) or high (219-295 ppm) dietary levels of either FB2 (FB2CM) or FB3 (FB3CM). Other groups were fed culture material of an FB1 producing isolate (FB1CM) providing 6.9, 53 or 303 ppm total fumonisins (FB1: FB2: FB3 = 1.0: 0.38: 0.15) and a tenth group was fed a control diet having no detectable fumonisins. One-half (n = 5/group) the animals were killed after three weeks, at which time the toxicological and histopathological effects of the three culture materials were similar, mimicked the effects of FB1, and included decreased body weight gains, serum chemical indicators of hepatotoxicity, decreased kidney weights, and apoptosis of hepatocytes and kidney tubular epithelium. FB1CM, FB2CM, and FB3CM affected sphingolipids, causing increased sphinganine to sphingosine ratios (Sa/So) in both liver and kidneys. The remaining animals (n = 5/group0 were fed a control diet for three additional weeks. All body weight and tissue specific effects, including increased Sa/So, induced by the FB2Cm, FB3CM and low level FB1CM diets were absent following the recovery period. Except for mild biliary lesions found in the high dose of FB1CM group and a few apoptotic hepatocytes present in one mid- and two high-dose FB1CM rats, no evidence of toxicity remained in these groups, following the recovery period.

Topics: Animals; Carboxylic Acids; Fumonisins; Fusarium; Humans; Kidney; Liver; Male; Mycotoxins; Organ Size; Rats; Rats, Sprague-Dawley; Sphingolipids; Weight Gain; Zea mays

The developmental toxicity of purified fumonisin B1 (FB1), a mycotoxin from the common corn fungus Fusarium moniliforme, was examined in Charles River rats. Pregnant rats were dosed orally on gestation days 3-16 at 0, 6.25, 12.5, 25 or 50 mg FB1/kg body weight/day. FB1 was not teratogenic at the doses tested. At 50 mg/kg, maternal toxicity (inappetence, emaciation, lethargy, death, resorption of entire litters) and foetal toxicity (increased number of late deaths, decreased foetal body weight, decreased crown rump length, increased incidence of hydrocephalus, increased incidence of skeletal anomalies) were seen. The foetal toxicity observed at 50 mg/kg may be related to maternal toxicity. Histopathological evaluation of tissues from dams of control and all treated groups revealed dose-related toxic changes in kidney and liver tissues. Acute toxic tubular nephrosis was seen in kidneys from all treated groups. Hepatocellular cytoplasmic alteration and individual cellular necrosis of the liver was seen in the two high-dose groups. Sphinganine (Sa) and sphingosine (So) were measured in day-17 adult and foetal tissues. Dose related increases in Sa/So ratios were seen in maternal liver, kidney, serum and brain, but there was no effect on foetal liver, kidney and brain. These data suggest that FB1 does not cross the placenta and further suggest that the observed foetal toxicity is a secondary response to maternal toxicity.

Topics: Animals; Carboxylic Acids; Eating; Embryonic and Fetal Development; Female; Fetus; Fumonisins; Kidney; Liver; Male; Mycotoxins; Organ Size; Pregnancy; Pregnancy, Animal; Rats; Rats, Inbred Strains; Reproduction; Sphingolipids; Teratogens; Weight Gain

Two diets containing no (<1.0 mg/ kg) or 95 mg of fumonisin B1 (FB1)/kg were fed to eight weanling Angora goats for 112 d. Dry matter intake, apparent nutrient digestibilities, serum chemistry profiles, sphingolipid concentrations, and persistency of FB1 in tissues were evaluated. No differences (P>.10) were found between control and treated goats in terms of DMI, apparent nutrient digestibilities, or ADG. Elevated concentrations (P<.10) of blood-borne enzymes such as aspartate aminotransferase, lactate dehydrogenase, and gamma glutamyl transpeptidase and increased concentrations of cholesterol and triglycerides indicated mild liver damage and kidney dysfunction in treated goats. Linear relationships (P<.10) were observed between these serum constituents and duration of FB1 exposure. The sphingolipid analysis of liver, kidney, and heart tissues showed elevated free sphinganine:free sphingosine ratios in the treated group. The elevated sphingolipid ratios were mainly due to increased concentrations of free sphinganine in tissues. However, without serum profile and sphingolipid analyses, fumonisin toxicosis would not have been recognized because treated animals showed no clinical signs of toxicosis throughout the trial. No measurable FB1 was present in liver, kidney, and heart tissues (detection limit of 1 ppm). However, further research is needed to analyze tissues for FB1 or its metabolites with a lower detection limit. In conclusion, goats can be fed for up to 112 d with diets containing 95 mg FB1/kg of diet without any overt signs of toxicosis and also without any effect on live weight gain.

Topics: Animal Feed; Animals; Blood Chemical Analysis; Carboxylic Acids; Carcinogens, Environmental; Digestion; Eating; Female; Food Contamination; Food Microbiology; Fumonisins; Fusarium; Goats; Kidney; Liver; Mycotoxins; Myocardium; Random Allocation; Sphingosine; Weight Gain

Dietary fumonisin B1 (FB1) levels of 250 and 500 mg FB1/kg increased the level of thiobarbituric acid reactive substances (TBARS) significantly (P < 0.05) in the liver of rats fed FB1 over 21 days. Levels of 10, 50 and 100 mg FB1/kg also markedly (not significantly) increased the level of TBARS in the liver homogenate. Subcellular fractionation of the liver of the rats fed the 250 mg FB1/kg diet, showed a marginally significant increase of TBARS in the plasma membranes (0.05 < P < 0.1) and a significant increase in the microsomes (P < 0.05). In vitro investigations in primary rat hepatocytes indicated that the level of TBARS was increased in a dose dependent manner associated with an increase in cytotoxicity. Addition of the antioxidant, alpha-tocopherol, significantly decreased the cytotoxicity whereas the level of TBARS was decreased to basal levels, suggesting that lipid peroxidation is likely to contribute to the cytotoxic effect of FB1. Addition of cumene hydroperoxide (CMHP) to primary hepatocytes exposed to FB1 for 44 h, enhanced the CMHP-induced TBARS release suggesting that the hepatocytes exposed to FB1 are more susceptible to chemically-induced oxidative stress. Free radical production could result in excessive cellular damage and/or metabolic abnormalities that are likely to be involved in FB1-induced altered growth responses and cell death in primary hepatocytes. The hepatotoxic effects and resultant oxidative damage induced by FB1 may be important during cancer induction in rat liver by this apparently non-genotoxic compound.

Topics: Animals; Carboxylic Acids; Cells, Cultured; Fumonisins; L-Lactate Dehydrogenase; Lipid Peroxidation; Liver; Male; Mycotoxins; Organ Size; Rats; Rats, Inbred F344; Vitamin E; Weight Gain

The individual and combined effects of feeding diets containing 300 mg fumonisin B1 (FB1), and 4 mg diacetoxyscirpenol (DAS) or 3 mg ochratoxin A (OA) were evaluated in two experiments using female turkey poults (Nicholas Large Whites) from day of hatch to 3 wk of age. When compared with controls, body weight gains were reduced 30% (Study 1) and 24% (Study 2) by FB1, 30% by DAS, 8% by OA, 46% by the FB1 and DAS combination, and 37% by the FB1 and OA combination. The efficiency of feed utilization was adversely affected by all treatments except FB1 in Experiment 2. Relative weights of the liver were significantly increased by all treatments except the DAS treatment. Serum concentrations of cholesterol were decreased and activities of aspartate aminotransferase and lactate dehydrogenase were increased and several hematological values were altered in poults fed FB1 alone and in combination with either DAS or OA. Results indicate additive or less than additive toxicity, but not toxic synergy, when poults are fed diets containing 300 mg FB1, and 4 mg DAS or 3 mg OA/kg of diet. The likelihood of encountering FB1, DAS, or OA at these concentrations in finished feed is small. However, under field conditions, other stress factors could alter the impact of these mycotoxins on the health and performance of poultry.

Topics: Animal Feed; Animals; Aspartate Aminotransferases; Body Weight; Carboxylic Acids; Cholesterol; Drug Interactions; Energy Metabolism; Erythrocyte Count; Female; Fumonisins; Fusarium; Hematocrit; L-Lactate Dehydrogenase; Liver; Mycotoxins; Ochratoxins; Organ Size; Trichothecenes; Triglycerides; Turkeys; Weight Gain

The individual and combined effects of feeding diets containing 300 mg fumonisin B1 (FB1), and 5 mg T-2 toxin (T-2)/kg of diet, or 15 mg/kg deoxynivalenol (DON, vomitoxin) from naturally contaminated wheat were evaluated in two studies in male broiler chicks from day of hatch to 19 or 21 d of age in Experiments 1 and 2, respectively. When compared with controls, body weight gains were reduced 18 to 20% by FB1, 18% by T-2, 2% by DON, 32% by the FB1 and T-2 combination, and 19% by the FB1 and DON combination. The efficiency of feed utilization was adversely affected by FB1 with or without T-2 or DON. Mortality ranged from none for the controls to 15% for the FB1 and T-2 combination. Relative weights of the liver and kidney were significantly increased by FB1 with or without T-2 or DON. Serum concentrations of cholesterol were increased in chicks fed FB1 with or without T-2 or DON. Activities of aspartate aminotransferase, lactate dehydrogenase, and gamma glutamyltransferase were increased in chicks fed FB1 at 300 mg/kg alone and in combination with T-2 or DON, indicating possible tissue damage and leakage of the enzymes into the blood. Results indicate additive toxicity when chicks were fed diets containing 300 mg FB1 and 5 mg T-2/kg of diet and less than additive toxicity when chicks were fed 300 mg FB1 and 15 mg DON/kg of diet. Of importance to the poultry industry is the fact that toxic synergy was not observed for either of these toxin combinations and the likelihood of encountering FB1 at this concentration in finished feed is small. However, under field conditions with additional stress factors, the toxicity of these mycotoxins could be altered to adversely affect the health and performance of poultry.

Topics: Animals; Blood Urea Nitrogen; Body Weight; Calcium; Carboxylic Acids; Carcinogens, Environmental; Chickens; Cholesterol; Diet; Drug Combinations; Fumonisins; Fusarium; gamma-Glutamyltransferase; Gizzard, Avian; Kidney; L-Lactate Dehydrogenase; Liver; Male; Organ Size; Serum Albumin; T-2 Toxin; Trichothecenes; Triticum; Weight Gain

To investigate the neurobehavioral and developmental effects of the mycotoxin, FB1, Sprague-Dawley rats were treated with FB1 on gestational days 13-20. In Experiment 1, FB1 was obtained from culture material and pregnant rats were gavaged with 0, 0.8 or 1.6 mg/kg. In Experiment 2, pregnant rats were gavaged with purified FB1 at doses of 0, 1.6 or 9.6 mg/kg. Offspring were evaluated on a battery of behavioral tests as well as measures of whole and regional brain weight. There were no effects on maternal weight gain, reproductive outcomes, or offspring body weight through adulthood in either experiment. Complex maze performance, open field and running wheel activity were not altered by prenatal FB1 treatment. In Experiment 2, acoustic startle response was depressed at two ages during the first or second block of 9 trials in males treated with purified FB1. Females exhibited no such alterations. Play behavior at PND 33, but not PND 26, was increased in males prenatally treated with 9.6 mg/kg relative to those treated with 1.6 mg/kg. There were no substantive treatment effects on regional brain weight. These results suggest that doses of < or = 9.6 mg purified FB1/kg and/or < or = 1.6 mg FB1/kg obtained from culture material cause minimal maternal toxicity and produce few development functional alterations. In addition, potential FB1-related functional alterations were evident only in males providing further support for a mild sex-specific effect for fumonisin.

Topics: Animals; Behavior, Animal; Carboxylic Acids; Eating; Female; Fetal Diseases; Fumonisins; Growth; Male; Maze Learning; Motor Activity; Mycotoxins; Nervous System Diseases; Pregnancy; Pregnancy, Animal; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Smell; Weight Gain

Objectives of this study were to test the hypothesis that fumonisin B1 (FB1) alters sphinganine (Sa) levels and myelin synthesis in the central nervous system of developing rats. FB1 (subcutaneous, 0.4 or 0.8 mg/kg/day) from postnatal days (PND) 3 to PND 12 resulted in a significant reduction of body weight gain and decreased survival rates. Both Sa levels and Sa/sphingosine (So) ratios were significantly increased in the brain of rats given 0.8 mg FB1/kg/day. To confirm the effect of limited nutrition on changes in the Sa levels and myelinogenesis, rats given 0.8 mg FB1/kg/day or treated by limited nutrition (temporary removal from dam during postnatal period) were compared to those in saline controls. Sa levels and Sa/So ratios were increased significantly in the 0.8 FB1-treated, but were not altered in the limited nutrition group. Myelin deposition in the corpus callosum and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) activities were decreased significantly in both nutritionally limited and FB1-exposed rats. These data indicate that sphingolipid metabolism in the central nervous system of developing rats is vulnerable to FB1 exposure. The hypomyelination associated with FB1-treatment may be mediated by limited nutrition.

Topics: Animal Nutritional Physiological Phenomena; Animals; Brain; Brain Chemistry; Carboxylic Acids; Chromatography, High Pressure Liquid; Enzyme Inhibitors; Female; Fumonisins; Histocytochemistry; Mycotoxins; Myelin Sheath; Pregnancy; Protein Kinase C; Rats; Rats, Sprague-Dawley; Sphingosine; Weight Gain

The modulating role of fumonisin B1 (FB1) on lipid biosynthesis was evaluated in a short-term (21 day) experiment using male Fischer rats fed high dietary levels (50, 100 and 250 mg FB1/kg) and in a long-term (2 yr) experiment using male BD IX rats fed low dietary levels (1, 10 and 25 mg FB1/kg) of FB1. The total serum and liver cholesterol was significantly (P < 0.01) increased in the rats fed 250 mg FB1/kg diet for 21 days, while the liver phospholipids, sphingomyelin and phosphatidylethanolamine (PE) were significantly decreased (P < 0.01) and increased (P < 0.05), respectively. In the long-term study, only PE was significantly (P < 0.05) increased in all the FB1-treated animals. Fatty acid (FA) analysis of PE indicated that C18:2n-6 was significantly increased (P < 0.05 to P < 0.01) in the FB1-treated rats of the short-term study, while it was markedly (not significantly) increased in phosphatidylcholine (PC). The same pattern was observed in the PC and PE fractions of the liver of the FB1-treated rats from the long-term studies, but the changes were not significant due to the small number (three rats per group) of rats analysed. The levels of C22:5n-6 and C22:6n-3 were also markedly decreased and increased respectively in the 10 and 25 mg FB1/kg-treated groups. When the FAs were determined in the total lipids in a larger number of rats (four to six animals per group) the level of C18:2n-6 was significantly increased in the 10 (P < 0.01) and 25 (P < 0.05) mg FB1/kg-treated groups. Similar effects were noticed in plasma PC with respect to the C18:5n-6 and C22:55n-6 in both the long- and short-term treated groups, except that C20:4n-6 was also lower in both cases. The total n-6 FAs and polyunsaturated FAs were significantly (P < 0.01) and markedly reduced in PC and PE, respectively, of the rats fed the 250 mg FB1/kg diet. In the long-term experiment the n-6/n-3 ratio was significantly (P < 0.01) decreased in PE and markedly lowered in PC due to a significant (P < 0.05) increase in the n-3 FAs of both phospholipid fractions. The sphinganine/sphingosine ratio was significantly (P < 0.05) altered in the liver of the rats fed the 100 and 250 mg FB1/kg diets for 21 days, while in the long-term study no significant changes were noticed in either the liver or sera. The present data indicate that FB1 affects lipid biosynthesis in rat liver and plasma differently, depending on the dietary level and duration of treatment. Alterations to the n-3 and n-6 FA biosynt

Topics: Animals; Carboxylic Acids; Carcinogens, Environmental; Cholesterol; Diet; Dose-Response Relationship, Drug; Fatty Acids; Fumonisins; Liver; Male; Organ Size; Phospholipids; Rats; Rats, Inbred F344; Weight Gain

Consumption of corn or corn-based products contaminated with Fusarium moniliforme/fumonisins has been associated with a variety of animal and human diseases and is a major food/feed safety issue. This study focused on the clinical toxicity and performance parameters in growing swing exposed to low to moderate levels of pure fumonisin B1 (FB.) for 8 weeks. Male (castrated) and female pigs were fed diets containing 0,0.1,1.0, and 10 mg FB1/kg diet (ppm). Weight gains and feed consumption were measured weekly. Blood samples were collected throughout the study, and various clinical and hematological parameters were measured. Because fumonisins are potent inhibitors of sphingolipid biosynthesis, sphinganine and sphingosine concentrations were determined in the liver, lung, and kidney. Organ weights and carcass quality were measured at the end of the trial. In general, male pigs were more adversely affected by FB1 in the diet than females. The average daily gain for males decreased by 8% for pigs fed 1.0 ppm and by 11% at 10.0 ppm, when compared to the control (0 ppm). Males fed 0.1 ppm showed an erratic growth pattern during the first 5 weeks of the experiment. Feed consumption for the same animals was somewhat higher than that of the controls during each of the first 4 weeks but thereafter was 6-7% lower each week as compared to controls. Female pigs fed FB1-diets showed a general enhancement of feed consumption until week 4. Among clinical chemistry parameters, cholesterol increased in males for the 1.0 and 10.0 ppm diets as compared to controls after 2 weeks, while the levels in both sexes were elevated for the 1.0 ppm diet only by the end of the experiment. Serum liver enzyme concentrations were altered during week 2 only. Changes were observed in the weight of the pancreas and adrenals for male pigs fed FB1 diets as compared to controls. The free sphinganine to free sphingosine ratio (biomarker of exposure in FB1-consuming animals) increased in all three organs for the 10 ppm diet, regardless of sex. The study indicated that FB1 can cause different effects at each dose level, at concentrations as low as 0.1 ppm (showing erratic growth) followed by a reduced growth and biochemical abnormalities in blood (1.0 ppm) and sphingolipid alterations in tissues (10.0 ppm). Some of these effects occurred below the exposure level that caused alteration in sphingolipid metabolism.

Topics: Adrenal Glands; Animal Feed; Animals; Biomarkers; Carcinogens, Environmental; Cholesterol; Diet; Female; Fumonisins; Kidney; Liver; Lung; Male; Mycotoxins; Organ Size; Pancreas; Sex Factors; Sphingosine; Swine; Tissue Distribution; Weight Gain

Male rats were gavaged with fumonisin B1 (FB1) once daily for 11 consecutive days at doses of 0, 1, 5, 15, 35, and 75 mg FB1/kg body weight. Urine osmolality (at 5-75 mg FB1/kg) and organic ion transport in kidney slices (at 5-75 mg FB1/kg) were reduced. Urinary excretion of protein (at 15-75 mg FB1/kg) and of the enzymes LDH (at 5-75 mg FB1/kg), NAG (at 5-75 mg FB1/kg) and GGT (at 15-75 mg FB1/kg) were increased. These findings were indicative of glomerular and tubular toxicity. Histopathologic changes in the kidney consisted of necrosis of tubular epithelia of variable extent accentuated in the inner cortex. These changes were present at 1 and 5 mg FB1/kg and were more pronounced at 15-75 mg FB1/kg. Serum enzymes indicative of hepatotoxicity (ALT, GGT) were elevated compared to controls at 75 mg FB1/kg only. There were noticeable increases in mitotic figures in hepatocytes at 35-75 mg FB1/kg, while single cell necroses were increasingly numerous from 15-75 mg FB1/kg. The kidneys were considered to be the primary target organs in this study.

Topics: Acetylglucosaminidase; Animals; Creatinine; Fumonisins; gamma-Glutamyltransferase; Kidney; Kidney Diseases; L-Lactate Dehydrogenase; Leukocyte Count; Liver; Male; Mycotoxins; Osmolar Concentration; Proteinuria; Rats; Rats, Sprague-Dawley; Transaminases; Urine; Weight Gain

The presence of mycotoxins in grains and feedstuffs causes not only animal health problems, but also a valid concern about the transmission of potentially toxic residues into animal-derived products intended for human consumption. In a series of studies at Agriculture and Agri-Food Canada, we investigated the biological fate of fumonisin B1 (FB1) in several food-producing animals (grower pigs, laying hens, dairy cattle), as well as monitored various parameters for evidence of toxicity in these species. In several experiments involving either single-dose protocols (iv, po) or longer-term feeding trials, the pharmacokinetic profiles of FB1 (purity > 95%) in these species were determined, including tissue accumulation and transmission of residues. Toxicological (and economical) implications such as performance (feed consumption, growth), productivity, and carcass quality were also measured when appropriate.

Topics: Absorption; Animal Feed; Animals; Body Burden; Cattle; Chickens; Eating; Female; Food Contamination; Fumonisins; Kinetics; Mycotoxins; Organ Specificity; Swine; Weight Gain

To examine the toxic effects of fumonisin B1 (FB1)-containing culture material and deoxynivalenol (DON)-contaminated wheat diets on barrows.. 24, 7-week-old crossbred barrows allotted to 4 equal groups of 3 replicates of 2 barrows/replicate.. Barrows were fed diets for 28 days that were formulated as follows: no additional FCM or DON/kg of feed (control); 100 mg FB1/kg of feed; 5 mg DON/kg of feed; or 100 mg FB1 plus 5 mg DON/kg of feed. Body weight and feed consumption were monitored weekly. On day 28, blood samples were obtained for serum biochemical, hematologic, and immunologic measurements. On day 29, barrows were euthanatized and necropsies were performed.. Analyzed mycotoxin content of diets were: none detected (control); 47 mg of FB1/kg of feed (FB1 diet); 4.5 mg of DON/kg of feed (DON diet); and 56 mg of FB1 and 3.7 mg of DON/kg of feed (FB1 plus DON diet). Differences were detected among groups of barrows for clinical performance, serum biochemical analytes, immunologic response, and histopathologic lesions.. Combining FB1-containing material and DON-contaminated wheat in the diets of growing barrows induces a more toxic response than that induced by either toxin singly. For many variables, the response could be described as additive; however, for some variables, responses were interactive in a greater-than-additive manner.. Caution should be exercised when formulating swine diets that could contain FB1 and DON, because the condition induced by their combination is more severe than that predicted for each mycotoxin's toxicity.

Topics: Animal Feed; Animals; Body Weight; Carboxylic Acids; Diet; Food Contamination; Fumonisins; Liver; Lung; Male; Mycotoxins; Orchiectomy; Organ Size; Swine; Triticum; Weight Gain

The effects of feeding Fusarium moniliforme culture material, containing known concentrations of fumonisin B1 (FB1), were studied in turkey poults. Day-old poults were allotted randomly to dietary treatments containing 0, 0.41, 0.82, 1.23, 1.64. 2.87, 4.10, 5.33, 6.56, and 7.79% fumonisin culture material (FCM). These levels of FCM supplied 0, 25, 50, 75, 100, 175, 250, 325, 400, and 475 mg FB1/kg of feed. Each dietary treatment was fed to six pen replicates of six poults each for 21 d. Poults fed FCM that supplied 325 to 475 mg FB1/kg diet had lower (P < 0.05) feed intakes and BW gains. Increased (P < 0.05) liver and pancreas weights were observed in poults fed FCM that supplied > or = to 175 mg FB1/kg. Poults fed FCM that supplied 400 and 475 mg FB1/kg diet had increased (P < 0.05) red blood cell counts and increased (P < 0.05) serum concentrations of gamma glutamyl transferase and aspartate aminotransferase. Compared with controls, poults fed FCM that supplied 25, and 75 to 475 mg FB1/kg had increased (P < 0.05) liver sphinganine:sphingosine ratios. Hepatocellular hyperplasia was mild at 75 and 100 mg FB1/kg diet, moderate to severe at 250 mg/kg FB1, and severe at 325 to 475 mg FB1/kg. Multifocal to generalized loss of cross striations and thinning of cardiomyocytes was observed in poults fed FCM that supplied 475 mg FB1/kg diet. Results indicated that diets containing < or = to 1.23% FCM that supplied > or = to 75 mg FB1 /kg are toxic to young turkeys.

Topics: Animals; Carboxylic Acids; Carcinogens, Environmental; Diet; Dose-Response Relationship, Drug; Energy Metabolism; Feeding Behavior; Female; Fumonisins; Fusarium; Hematocrit; Liver; Organ Size; Pancreas; Proventriculus; Turkeys; Weight Gain

Diets containing 300 mg fumonisin B1 (FB1)/kg of feed and 5 mg T-2 toxin/kg of feed singly or in combination were fed to female turkey poults (Nicholas Large White) from day of hatch to 21 d of age. When compared with controls, 21-d body weight gains were reduced 21% by FB1, 26% by T-2, and 47% by the combination. the efficiency of feed utilization was adversely affected by FB1 and the combination of FB1 and T-2. Relative weights (grams/100 g BW) of the liver and gizzard were increased in poults fed the FB1 and the combination diets; whereas, the relative weight of the pancreas was increased in all treated groups. All poults were scored for oral lesions using a scale of 1 to 4 (1 = no visible lesions, 4 = severe lesions). Oral lesions were present in all poults fed the T-2 diet (average score of 3.29) or the combination diet (average score of 3.54). Serum concentration of cholesterol was decreased and lactate dehydrogenase activity was increased in poults fed the FB1 and combination diets. The activity of aspartate aminotransferase and the values for red blood cells, hemoglobin, and hematocrit were increased only in poults fed the combination diet. Inorganic phosphorus concentration was decreased only in poults fed the combination diet. The increased toxicity in poults fed the combination diet for most variables can best be described as additive, although some variables not altered by FB1 or T-2 singly were significantly affected by the combination, indicating that the combination may pose a potentially greater problem to the turkey industry than either of the mycotoxins individually.

Topics: Animals; Aspartate Aminotransferases; Female; Fumonisins; L-Lactate Dehydrogenase; Mouth Diseases; Mycotoxins; Organ Size; T-2 Toxin; Turkeys; Weight Gain

Aflatoxin (AF)-contaminated and fumonisin B1 (FB1)-contaminated (culture material from Fusarium moniliforme) diets were fed singly and in combination to growing cross-bred barrows. Six barrows (3 replicates of 2 each; mean body weight, 17.5 kg) per group were fed: 0 mg of AF and 0 mg of FB1/kg of feed (control); 2.5 mg of AF/kg of feed; 100 mg of FB1/kg of feed; or 2.5 mg of AF plus 100 mg of FB1/kg of feed for 35 days. The effects on production performance, serum biochemical, hematologic, immunologic, and pathologic measurements were evaluated. Body weight, gain, and feed consumption were significantly (P < 0.05) decreased by AF and AF plus FB1 diets. The FB1 diet decreased feed consumption, and although body weight was numerically decreased, it was not statistically significant. Aflatoxin increased serum gamma-glutamyltransferase (GGT) activity and total iron concentration and decreased urea nitrogen concentration and unsaturated iron-binding capacity. The FB1-alone diet increased serum GGT activity, whereas the AF plus FB1 diet increased serum aspartate transaminase, cholinesterase, alkaline phosphatase, and GGT activities, increased RBC count, triglycerides, and total iron concentrations, and decreased unsaturated iron-binding capacity and urea nitrogen concentration. For the most part, the effects of the AF plus FB1 diet on body weight and hematologic measurements could be considered additive. However, the effect of the AF plus FB1 diet on cholinesterase and alkaline phosphatase activities was greater than additive and was a synergistic response. One pig in the FB1-diet group and 2 pigs in the combination-diet group died. Postmortem lesions in pigs of the FB1-diet group consisted of ascites and increased liver weight. Observations at necropsy for pigs of the AF plus FB1-diet group consisted of hydrothorax, ascites, pulmonary edema, gastric erosions and ulceration, and increased liver and spleen weights. The AF diet increased relative liver weight and resulted in liver that was pale, rubbery, and resistant to cutting. Histologic lesions consisted of hepatic necrosis or degeneration, or both, with variable degrees of bile duct proliferation in barrows of the AF-diet groups. Renal tubular nephrosis was observed in barrows of the FB1-diet group, but this was not consistent in the AF plus FB1-diet group. Cell-mediated immunity, as measured by mitogen-induced lymphoblastogenic stimulation index, was decreased in barrows of the AF and FB1-diet groups, and v

Topics: Aflatoxins; Alkaline Phosphatase; Animal Feed; Animals; Aspartate Aminotransferases; Blood Urea Nitrogen; Body Weight; Carcinogens; Carcinogens, Environmental; Cholinesterases; Chromatography, High Pressure Liquid; Erythrocyte Count; Fumonisins; Fusarium; gamma-Glutamyltransferase; Iron; Liver; Lung; Male; Mycotoxins; Organ Size; Random Allocation; Spleen; Swine; Weight Gain

The individual and combined effects of fumonisin B1 (FB1) and aflatoxin B1 (AF) were evaluated using a 2 x 2 factorial with treatments of 0 and 75 mg FB1/kg feed and 0 and 200 micrograms AF/kg feed. Each of the four diets was fed to eight pen replicates of six poults from Day 1 to 21. Body weight gain was reduced (P < .05) by AF and the FB1-AF combination. Poults fed AF or the FB1-AF combination were less efficient (P < .05) in converting feed to gain. Fumonisin B1 increased (P < .05) liver weights whereas AF and the FB1-AF combination increased (P < .05) spleen weights. The AF and the FB1-AF combination decreased (P < .05) serum concentrations of albumin, total protein, and cholesterol. Fumonisin B1 and the FB1-AF combination increased (P < .05) serum sphinganine:sphingosine (SA:SO) ratios. Treatment-associated lesions were observed only in the liver. Hepatocellular hyperplasia and biliary hyperplasia were seen in poults fed 75 mg FB1/kg and 200 micrograms AF/kg, respectively. The combination of FB1 and AF caused an increased primary immune response to sheep red blood cells. However, the phytohemagglutinin delayed hypersensitivity response was not affected by dietary treatment. These data indicate that FB1 and AF, alone and in combination, can adversely affect poult performance and health at these dietary concentrations.

Topics: Aflatoxin B1; Animals; Eating; Food Contamination; Fumonisins; Fusarium; Hyperplasia; Liver; Mycotoxins; Organ Size; Sphingolipids; Turkeys; Weight Gain; Zea mays

The purpose of this study was to investigate potential detrimental effects of fumonisin B1 on the developing hamster. In experiments 1 and 2, timed-bred hamsters were dosed with 0.0 to 12.0 mg fumonisin B1/kg from day 8 to day 10 or day 12 of gestation. Clinical signs of material toxicity were not observed. Pregnant animals had reduced weight gains and lower total bilirubin levels than nonpregnant females. Hamsters were euthanized on day 15 of gestation. Histologic evaluation revealed autolytic placental changes expected in terminal gestation, as well as more advanced placental necrosis in association with fetal resorptions. Mean fetal weights and crown-rump lengths of living term fetuses on a per-litter basis did not differ between untreated controls and treated animals given 6.0 mg fumonisin B1/kg or less. However, at higher doses of fumonisin B1, there was an increased incidence of prenatal losses (deaths and resorptions). A greater percentage of litters had 1 or more fetuses affected, and a greater percentage of total fetuses were lost/litter as the fumonisin dosage increased. At 12.0 mg/kg, all litters were affected and 100% of the fetuses were dead and resorbing. Fumonisin B1 appears a developmental toxicant in hamsters. Toxicity is manifest by increased numbers of prenatal deaths and resorptions at doses that do not induce clinicopathologic evidence of maternal toxicity.

Topics: Animal Feed; Animals; Carcinogens, Environmental; Cricetinae; Embryonic and Fetal Development; Female; Fetal Resorption; Fetus; Food Microbiology; Fumonisins; Fusarium; Gestational Age; Liver; Liver Function Tests; Mesocricetus; Mycotoxins; Pregnancy; Weight Gain; Zea mays

Two hundred twenty-eight male chicks (Columbia x New Hampshire) were given feed amended with autoclaved culture material (CM) of Fusarium proliferatum Containing fumonisin B1 (FB1), fumonisin B2 (FB2) and moniliformin in 3 separate feeding trials. Purified FB1 and moniliformin were given separately and in combination in a fourth feeding trial. Birds were given amended rations at day 1 (Trial 1 and 4), day 7 (Trial 2), and day 21 (Trial 3) and their respective ration was given for 28 days (Trial 1), 21 days (Trial 2), 7 days (Trial 3), and 14 days (Trial 4). FB1 concentrations were 546, 193, and 61 ppm; FB2 were 98, 38 and 14 ppm; and moniliformin were 367, 193, and 66 ppm in the first 3 feeding trial regimens. Chicks in Trial 4 were given dietary concentrations of purified FB1 at 274 and 125 ppm, and moniliformin at 154 and 27 ppm. FB1 and moniliformin, both alone and in combination, produced dose-responsive clinical signs, reduced weight gains and mortality in chicks. Age of birds given amended feeds had little difference in the clinical response; however, those given the rations from days 7 or 21 were slightly less susceptible than those given rations beginning at 1 day of age. Additive effects were noted when the toxins were given in combination. When toxins were given separately, adverse effects took longer to occur. A system to monitor pattern and rate of defecation (RD) was developed for assessing the chicks' approach to feed, water and heat source as illness progressed. Our results indicate that chicks fed corn heavily infected with F. proliferatum under field conditions could suffer acute death similar to that described for 'spiking mortality syndrome' during the first 3 weeks of age.

Topics: Animal Feed; Animals; Chickens; Culture Media, Conditioned; Cyclobutanes; Fumonisins; Fusarium; Male; Mycotoxins; Poultry Diseases; Weight Gain

The effects of dietary fumonisin B1 were evaluated in young turkey poults. The experimental design consisted of 3 treatments, with 24 female turkey poults allotted randomly per treatment. Day-old poults were fed diets containing 0 mg (feed control), 100 mg, and 200 mg fumonisin B1/kg feed for 21 days. Body weight gains and efficiency of feed conversion decreased linearly with increasing dietary fumonisin. Liver, kidney, and pancreas weights increased linearly with increasing dietary fumonisin, and spleen and heart weights decreased. Serum aspartate aminotransferase levels increased with increasing dietary fumonisin, and serum cholesterol; alkaline phosphatase, mean cell volume, and mean cell hemoglobin all decreased. Biliary hyperplasia, hypertrophy of Kupffer's cells, thymic cortical atrophy, and moderate widening of the proliferating and degenerating hypertrophied zones of tibial physes were present in poults fed diets containing fumonisin B1. Results indicate that fumonisin B1, from Fusarium moniliforme culture material, is toxic in young poults, and the poult appears to be more sensitive to fumonisin than the broiler chick.

Topics: Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Atrophy; Body Weight; Carcinogens, Environmental; Cholesterol; Female; Fumonisins; Heart; Kidney; Liver; Mycotoxins; Myocardium; Organ Size; Pancreas; Spleen; Thymus Gland; Turkeys; Weight Gain

Fumonisin B1 (FB1), a recently identified mycotoxin produced by Fusarium moniliforme in corn, has been shown to cause death in swine due to pulmonary edema, an apparently species specific effect, and to interfere with sphingolipid metabolism in vitro. Here we characterize the toxicity of fumonisins, using female cross-bred swine weighing 6 to 13 kg, and present a hypothesis regarding the mechanism of fumonisin-induced pulmonary edema in swine. FB1 was given daily intravenously (IV) to pig 1 for 9 days for a total of 72 mg (7.9 mg/kg) and to pig 2 for 4 days for a total of 67 mg (4.6 mg/kg). Pig 3 (control) was given saline IV for 9 days. Corn screenings naturally contaminated with FB1 (166 ppm) and FB2 (48 ppm) were fed to pigs 4, 5, and 6, and ground corn was fed to pigs 7 and 8 (controls). Pigs 4 and 7 were killed on day 5; pig 5 was found dead on day 6; and pigs 6 and 8 were killed on day 15. Pigs 4 and 5 had ingested 187 and 176 mg total fumonisins, respectively, while pig 6 had ingested 645 mg. Feed consumption had decreased in pigs fed corn screenings, with an additional sharp decrease prior to onset of clinical signs. Increases in serum liver enzymes, total bilirubin, and cholesterol were present, but electrocardiograms, heart rate, and body temperature were unaffected. Pigs dosed IV with FB1, developed mild intermittent respiratory abnormalities, while those fed screenings developed respiratory distress within 5 days. Mild interstitial pulmonary edema was observed in pig 1. Severe interstitial pulmonary edema, pleural effusion, and increased lung wet/dry weight ratio were observed in pigs 4 and 5. All pigs given fumonisin (either IV or orally) had hepatic changes characterized by hepatocyte disorganization and necrosis; pancreatic acinar cell degeneration was also observed. Ultrastructural changes in orally dosed swine included loss of sinusoidal hepatocyte microvilli; membranous material in hepatic sinusoids; and multilamellar bodies in hepatocytes, Kupffer cells, pancreatic acinar cells and pulmonary macrophages. Pulmonary intravascular macrophages (PIMs) contained large amounts of membranous material. Thus, the target organs of fumonisin in the pig are the lung, liver, and pancreas. At lower doses, slowly progressive hepatic disease is the most prominent feature, while at higher doses, acute pulmonary edema is superimposed on hepatic injury and may cause death. We hypothesize that altered sphingolipid metabolism causes hepatocellular damage res

Topics: Administration, Oral; Animal Feed; Animals; Catheters, Indwelling; Eating; Female; Fumonisins; Heart Rate; Infusions, Intravenous; Liver; Lung; Microscopy, Electron; Mycotoxins; Pancreas; Respiration; Specific Pathogen-Free Organisms; Swine; Weaning; Weight Gain