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Toxicological Sciences 60, 379-384 (2001)
Copyright © 2001 by the Society of Toxicology

SYSTEMS TOXICOLOGY

Fumonisin B1 Increases Serum Sphinganine Concentration but Does Not Alter Serum Sphingosine Concentration or Induce Cardiovascular Changes in Milk-Fed Calves

Sheerin Mathur*, Peter D. Constable*,1, Robert M. Eppley{dagger}, Mike E. Tumbleson{ddagger}, Geoffrey W. Smith*, William J. Tranquilli*, Dawn E. Morin* and Wanda M. Haschek§

* Departments of Veterinary Clinical Medicine, {ddagger} Veterinary Biosciences, and § Veterinary Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana, Illinois 61802; and {dagger} U.S. Food and Drug Administration, Washington, DC

Fumonisin B1 is the most toxic and commonly occurring form of a group of mycotoxins that alter sphingolipid biosynthesis and induce leukoencephalomalacia in horses and pulmonary edema in pigs. Purified fumonisin B1 (1 mg/kg, iv, daily) increased serum sphinganine and sphingosine concentrations and decreased cardiovascular function in pigs within 5 days. We therefore examined whether the same dosage schedule of fumonisin B1 produced a similar effect in calves. Ten milk-fed male Holstein calves were instrumented to obtain blood and cardiovascular measurements. Treated calves (n = 5) were administered purified fumonisin B1 at 1 mg/kg, iv, daily for 7 days and controls (n = 5) were administered 10 ml 0.9% NaCl, iv, daily. Each calf was euthanized on day 7. In treated calves, serum sphinganine concentration increased from day 3 onward (day 7, 0.237 ± 0.388 µmol/l; baseline, 0.010 ± 0.007 µmol/l; mean ± SD), whereas, serum sphingosine concentration was unchanged (day 7, 0.044 ± 0.065 µmol/l; baseline, 0.021 ± 0.025 µmol/l). Heart rate, cardiac output, stroke volume, mean arterial pressure, mean pulmonary artery pressure, pulmonary artery wedge pressure, central venous pressure, plasma volume, base-apex electrocardiogram, arterial Po2, and systemic oxygen delivery were unchanged in treated and control calves. Fumonisin-treated calves developed metabolic acidosis (arterial blood pH, 7.27 ± 0.11; base excess, –9.1 ± 7.6 mEq/l), but all survived for 7 days. We conclude that calves are more resistant to fumonisin B1 cardiovascular toxicity than pigs.

Key Words: fumonisin; sphingosine; sphinganine; sphingolipid; cardiovascular toxicity; metabolic acidosis.


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S. Mathur, P. D. Constable, R. M. Eppley, A. L. Waggoner, M. E. Tumbleson, and W. M. Haschek
Fumonisin B1 Is Hepatotoxic and Nephrotoxic in Milk-Fed Calves
Toxicol. Sci., April 1, 2001; 60(2): 385 - 396.
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