title: Characterization of fumonisin toxicity in orally and intravenously dosed swine.
abstract: 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)
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana 61801.
authors.forename: W M
authors.initials: WM
authors.lastname: Haschek
authors.forename: G
authors.initials: G
authors.lastname: Motelin
authors.forename: D K
authors.initials: DK
authors.lastname: Ness
authors.forename: K S
authors.initials: KS
authors.lastname: Harlin
authors.forename: W F
authors.initials: WF
authors.lastname: Hall
authors.forename: R F
authors.initials: RF
authors.lastname: Vesonder
authors.forename: R E
authors.initials: RE
authors.lastname: Peterson
authors.forename: V R
authors.initials: VR
authors.lastname: Beasley
mesh_terms: D000284:Administration, Oral; D000821:Animal Feed / Q000633:toxicity; D000818:Animals; D002408:Catheters, Indwelling / Q000662:veterinary; D004435:Eating / Q000187:drug effects; D005260:Female; D037341:Fumonisins; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous / Q000662:veterinary; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008168:Lung / Q000187:drug effects* / Q000648:ultrastructure; D008854:Microscopy, Electron; D009183:Mycotoxins / Q000008:administration & dosage / Q000633:toxicity*; D010179:Pancreas / Q000187:drug effects / Q000648:ultrastructure; D012119:Respiration / Q000187:drug effects; D013047:Specific Pathogen-Free Organisms; D013552:Swine / Q000097:blood / Q000502:physiology*; D014886:Weaning; D015430:Weight Gain / Q000187:drug effects
chemical_list: D037341:Fumonisins; D009183:Mycotoxins; C056933:fumonisin B1