Temporal and dose-response features in swine fed corn screenings contaminated with fumonisin mycotoxins.

Fumonisin B1 (FB1), a mycotoxin produced by Fusarium moniliforme and F. proliferatum, induces liver damage and pulmonary edema in swine. We examined the temporal and dose-response features of FB1 toxicosis in male weanling crossbred pigs fed nutritionally balanced diets, containing corn screenings naturally contaminated with fumonisins, for 14 days. Total fumonisins (FB1 and FB2) in diets 1 through 6 were assayed at 175, 101, 39, 23, 5, and < 1 ppm (below detectable concentrations), respectively. Clinical signs, serum biochemical alterations, and morphologic changes were evaluated. Pigs were weighed, and bled for hematologic and clinical chemistry evaluation on days 5 and 14. They were euthanized on day 14, or earlier if respiratory distress was observed. Respiratory distress developed in 3/5 pigs fed diet 1 between days 4 and 6 due to severe pulmonary edema and pleural effusion. Histologic evidence of hepatic injury was present in all pigs fed diets 1 and 2, 3/5 on diet 3, and 1/5 on diet 4. Serum bilirubin and cholesterol concentrations, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and arginase (ARG) activities were elevated in pigs fed diets 1 and 2. Based on liver histopathology, the no observed adverse effect level (NOAEL) for fumonisin toxicity in swine was < 23 ppm total fumosins for the 14-day period. Based on regression analyses of the clinical chemistry profiles at 14 days, the NOAEL was < 12 ppm, with ALP being the most sensitive parameter. In conclusion, pulmonary edema occurred only at the highest fumonisin concentration (175 ppm), while liver damage occurred at much lower concentrations with a NOAEL of < 12 ppm.

Retina, brain and blood cholinesterase levels in cats treated with oral dichlorvos.

Dichlorvos (DDVP) is used as an antihelmetic, principally in dogs, cats, pigs and horses. Retina, whole blood, erythrocyte, plasma and brain cholinesterase (ChE) activities were monitored following DDVP exposure in cats to establish their use as indicators of exposure to a ChE inhibitor. Following DDVP exposure, whole blood ChE activity was 16.8% of preexposure, erythrocyte ChE activity was 33% of preexposure, and plasma ChE was 19% of preexposure values. Brain and retinal ChE activities were reduced to 45% and 43% of control values. Retinal ChE paralleled brain activity.

Characterization of fumonisin toxicity in orally and intravenously dosed swine.

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 resulting in release of membranous material into the circulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Relationship between fumonisin contamination of feed and mystery swine disease. A case-control study.

Fumonisin is a recently identified mycotoxin that has been shown to be the cause of pulmonary edema disease in swine and leukoencephalomalacia in horses. Mystery Swine Disease (MSD), is an economically devastating disease complex of unknown etiology that has been reported to have occurred in several swine producing states since 1988. To determine the relationship between MSD and fumonisin, a case-control study was carried out in Illinois in mid-1990. Feed samples collected from 12 case and 9 control farms were analyzed for fumonisin. Sera from swine on all farms was screened for titers against encephalomyocarditis (EMC) virus and concentrations of alpha-1 acid glycoprotein (an acute phase reactive protein). Fumonisin concentrations greater than or equal to 20 ppm were found on 1 control farm (1/9) and 8 case farms (8/12). Titers against EMC virus (greater than or equal to 1:16) were found on 5 control farms (5/9) and on 6 case farms (6/12). Farms with greater than or equal to 20 ppm fumonisin in the feed were at significantly increased risk (OR = 11.2, Fisher's exact test p = 0.037) for MSD. Furthermore, the pi2 test for trend was (p = 0.017), meaning that as the level of fumonisin in the feed increased, the risk of MSD also increased. The presence of EMC virus titers in the sow herd was not a significant risk for MSD (OR = 1.25, Fisher's exact test p = 0.75). Alpha-1 acid glycoprotein concentrations obtained from a 2-week old nursing pigs differed significantly (p = 0.0005) between MSD case and control herds.

Reversal of cholinesterase inhibition and clinical signs and the postmortem findings in mice after intraperitoneal administration of anatoxin-a(s), paraoxon or pyridostigmine.

The reversibility of inhibition of plasma, red blood cell (RBC), and diaphragm cholinesterase (ChE) and clinical signs in mice given anatoxin-a(s) [antx-a(s)], a ChE inhibitor from Anabaena flos-aquae NRC-525-17, were characterized and compared with the effects of 2 known ChE inhibitors, the organophosphorus compound paraoxon and the carbamate pyridostigmine bromide. To follow recovery of ChE activity, mice were given either a control solution or an LD40 dose of one of the toxicants ip and killed at time points up to 8 d postdosing. After dosing, mice were monitored for diarrhea, fasciculations, respiratory difficulty, salivation, and tremors. In general, clinical signs in mice given antx-a(s) persisted longer than in mice given pyridostigmine and were more similar in duration to the clinical signs in mice given paraoxon. Histologic lesions were not detected in tissues of mice killed after administration of antx-a(s). Anatoxin-a(s) inhibited lesions were diaphragm ChE for greater than 1 but less than 2 d and RBC ChE for 8 d. The time required for recovery from Antx-a(s)-induced inhibition of ChE in plasma, RBC, and diaphragm was similar to or longer than that with paraoxon and longer than that with pyridostigmine. Based on the duration of antx-a(s) induced clinical signs and ChE inhibition in mice, antx-a(s) appears to be an in vivo irreversible inhibitor of ChE.

Enzymatic-spectrophotometric method for determination of cholinesterase activity in whole blood: collaborative study.

Ten collaborating laboratories assayed 4 blind duplicate pairs of whole bovine blood for cholinesterase activity. The 4 sample pairs ranged from normal (100%) to severely organo-phosphorus-inhibited (less than 10%) activity. Collaborators also received commercially available human lyophillized serum as an external control and a chromate solution to evaluate spectrophotometer performance. The Ellman kinetic assay was performed on a 1:1000 dilution of the whole blood in pH 8.0 phosphate buffer. The method monitors the increase in absorbance at 412 nm caused by formation of 5-thio-2-nitrobenzoic acid (yellow reaction product). Repeatability standard deviations (RSDr) ranged from 4.30 to 14.2%; reproducibility standard deviations (RSDR) ranged from 6.99 to 19.3%. The lower limit of detection was estimated to be 0.10 mumole/mL/min. The method has been approved interim official first action by AOAC.

Comparison of effects of anatoxin-a(s) and paraoxon, physostigmine and pyridostigmine on mouse brain cholinesterase activity.

Anatoxin-a(s), an alkaloid neurotoxin from the freshwater cyanobacterium, Anabaena flos-aquae NRC-525-17, was compared to paraoxon, physostigmine and pyridostigmine for effects on brain cholinesterase after i.p. injection into Balb/c mice. The duration of clinical signs in mice injected with anatoxin-a(s) persisted longer than in mice given the carbamates and was comparable with that of paraoxon. Anatoxin-a(s) did not inhibit brain cholinesterase activity suggesting that this toxin is unable to cross the blood-brain barrier.