Fumonisin B(1) increases serum sphinganine concentration but does not alter serum sphingosine concentration or induce cardiovascular changes in milk-fed calves

Toxicol Sci. 2001 Apr;60(2):379-84. doi: 10.1093/toxsci/60.2.379.

Abstract

Fumonisin B(1) 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 B(1) (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 B(1) 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 B(1) 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 micromol/l; baseline, 0.010 +/- 0.007 micromol/l; mean +/- SD), whereas, serum sphingosine concentration was unchanged (day 7, 0.044 +/- 0.065 micromol/l; baseline, 0.021 +/- 0.025 micromol/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 Po(2), 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 B(1) cardiovascular toxicity than pigs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acidosis, Respiratory / chemically induced
  • Animals
  • Animals, Suckling / blood*
  • Animals, Suckling / physiology
  • Carboxylic Acids / administration & dosage
  • Carboxylic Acids / toxicity*
  • Cattle
  • Fumonisins*
  • Heart Ventricles / drug effects
  • Heart Ventricles / metabolism
  • Hematologic Tests
  • Hemodynamics / drug effects*
  • Hemodynamics / physiology
  • Injections, Intravenous
  • Male
  • Milk
  • Mycotoxins / administration & dosage
  • Mycotoxins / toxicity*
  • Myocardium / metabolism
  • Sphingosine / analogs & derivatives*
  • Sphingosine / blood*

Substances

  • Carboxylic Acids
  • Fumonisins
  • Mycotoxins
  • fumonisin B1
  • Sphingosine
  • safingol