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Development of Fumonisin-Induced Hepatotoxicity and Pulmonary Edema in Orally Dosed Swine: Morphological and Biochemical Alterations

Department of Veterinary Pathobiology, University of Illinois, Urbana, Illinois 61802

Val R. Beasley

Department of Biosciences, University of Illinois, Urbana, Illinois 61802

Ronald M. Weigel

Department of Veterinary Pathobiology, University of Illinois, Urbana, Illinois 61802

Helen M. Parker

Department of Veterinary Pathobiology, University of Illinois, Urbana, Illinois 61802

Mike E. Tumbleson

Department of Biosciences, University of Illinois, Urbana, Illinois 61802

Charles W. Bacon

Toxicology and Mycotoxin Research Unit, Agricultural Research Service, U.S. Department of Agriculture, Athens, Georgia 30604

Filmore I. Meredith

Toxicology and Mycotoxin Research Unit, Agricultural Research Service, U.S. Department of Agriculture, Athens, Georgia 30604

Wanda M. Haschek

Department of Veterinary Pathobiology, University of Illinois, Urbana, Illinois 61802, whaschek{at}uiuc.edu

The fumonisin (FB) mycotoxins induce liver injury in all species but induce fatal pulmonary edema (PE) only in pigs. They inhibit ceramide synthase in the sphingolipid biosynthetic pathway. To study the pathogenesis of PE, we examined the early events in the development of FB-induced PE and hepatotoxicity in pigs. Pigs were fed FB-contaminated culture material at 20 mg fumonsin B₁ (FB ₁)/kg body weight/day. Groups of 4 pigs were to be euthanatized on 0, 1, 2, 3, 4, or 5 days after initial exposure to FB or when PE developed. Pigs developed PE beginning on day 3; none survived beyond day 4. Progressive elevations in hepatic parameters, including serum enzymes, bile acids, total bilirubin, and histologic changes, began on day 2. Early histologic changes in the lung (day 2) consisted of perivascular edema followed by interlobular and peribronchial edema. Ultrastructurally, alveolar endothelial cells contained unique accumulations of membranous material in the cytocavitary network beginning on day 2. Marked elevations in sphinganine, sphingosine, and their ratio began on day 1 for all tissues whether affected morphologically (lung, liver) or not (kidney, pancreas). The membranous material in endothelial cells may be accumulations of sphingoid bases with damage to the cytocavitary network. Thus, FB induces early elevations in sphingolipids and hepatic injury, followed by alveolar endothelial damage, which may be the critical event in the pathogenesis of PE in pigs.

Key Words: Fusarium moniliforme • sphinganine • sphingosine • liver • lung • sphingolipids • endothelial cells • ultrastructure

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Toxicologic Pathology, Vol. 26, No. 6, 777-788 (1998)
DOI: 10.1177/019262339802600610


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