Alteration of tissue and serum sphinganine to sphingosine ratio: An early biomarker of exposure to fumonisin-containing feeds in pigs

Ronald T. Riley, Nyeon Hyoung An, Jency L. Showker, Hwan Soo Yoo, William P. Norred, William J. Chamberlain, Elaine Wang, Alfred H. Merrill, Gideon Motelin, Val Richard Beasley, Wand M. Haschek

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Abstract

Fumonisins are a group of naturally occurring compounds produced by the fungus Fusarium moniliforme. They are believed to be the etiologic agent of several animal diseases associated with consumption of corn-based feeds including porcine pulmonary edema. Recently it was shown in vitro that fumonisins are specific inhibitors of sphingosine and sphinganine N-acyltransferases. Inhibition of these enzymes in cultured cells results in the accumulation of free long chain sphingoid bases, specifically sphingosine and sphinganine, and the depletion of complex sphingolipids. In this study, tissues and serum from male SPF pigs fed a nutritionally balanced diet containing corn or corn screenings naturally contaminated with fumonisins for up to 14 days were analyzed for free sphingoid bases and complex sphingolipids. Total fumonisins (B1 and B2) in the diets were analyzed at 0 (<1), 5, 23, 39, 101, and 175 ppm. Pulmonary edema only occurred at 175 ppm, while histologic liver damage was present at ≥23 ppm, and serum liver enzymes were significantly elevated at ≥ 101 ppm. The results of this study show that free sphinganine is elevated in liver, lung, and kidney, from pigs consuming feeds containing fumonisins at total fumonisin concentrations of 23 ppm or greater. Sphingosine is also elevated in a dose-dependent manner, but to a lesser extent than sphinganine. The consequence of this differential inhibition is that the ratio of sphinganine to sphingosine increases, suggesting that sphinganine N-acyltransferase is the preferred target for fumonisins. Elevation of free sphinganine and free sphingosine in serum paralleled the increases in tissues. Statistically significant increases in the ratio were observed at feed concentrations as low as 5 ppm total fumonisins and in pigs (at higher concentrations) in which other serum biochemistry parameters and tissue morphology were not altered. Elevated ratios were also observed in serum from pigs fed pure fumonisin B1. The sensitivity of the ratio indicates that it could serve as an effective biomarker for consumption of fumonisin-containing feeds. In addition, the data supports the hypothesis that inhibition of sphingosine and sphinganine N-acyltransferase plays an important role in the pathogenesis of animal diseases associated with consumption of feed containing fumonisins.

Original languageEnglish (US)
Pages (from-to)105-112
Number of pages8
JournalToxicology and Applied Pharmacology
Volume118
Issue number1
DOIs
StatePublished - Jan 1 1993

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Fumonisins
Sphingosine
Biomarkers
Swine
Tissue
Serum
Acyltransferases
Sphingosine N-Acyltransferase
Liver
Zea mays
Animal Diseases
Sphingolipids
Pulmonary Edema
Nutrition
Animals
Diet
safingol
Biochemistry
Fusarium
Enzymes

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

Cite this

Riley, Ronald T. ; An, Nyeon Hyoung ; Showker, Jency L. ; Yoo, Hwan Soo ; Norred, William P. ; Chamberlain, William J. ; Wang, Elaine ; Merrill, Alfred H. ; Motelin, Gideon ; Beasley, Val Richard ; Haschek, Wand M. / Alteration of tissue and serum sphinganine to sphingosine ratio : An early biomarker of exposure to fumonisin-containing feeds in pigs. In: Toxicology and Applied Pharmacology. 1993 ; Vol. 118, No. 1. pp. 105-112.
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title = "Alteration of tissue and serum sphinganine to sphingosine ratio: An early biomarker of exposure to fumonisin-containing feeds in pigs",
abstract = "Fumonisins are a group of naturally occurring compounds produced by the fungus Fusarium moniliforme. They are believed to be the etiologic agent of several animal diseases associated with consumption of corn-based feeds including porcine pulmonary edema. Recently it was shown in vitro that fumonisins are specific inhibitors of sphingosine and sphinganine N-acyltransferases. Inhibition of these enzymes in cultured cells results in the accumulation of free long chain sphingoid bases, specifically sphingosine and sphinganine, and the depletion of complex sphingolipids. In this study, tissues and serum from male SPF pigs fed a nutritionally balanced diet containing corn or corn screenings naturally contaminated with fumonisins for up to 14 days were analyzed for free sphingoid bases and complex sphingolipids. Total fumonisins (B1 and B2) in the diets were analyzed at 0 (<1), 5, 23, 39, 101, and 175 ppm. Pulmonary edema only occurred at 175 ppm, while histologic liver damage was present at ≥23 ppm, and serum liver enzymes were significantly elevated at ≥ 101 ppm. The results of this study show that free sphinganine is elevated in liver, lung, and kidney, from pigs consuming feeds containing fumonisins at total fumonisin concentrations of 23 ppm or greater. Sphingosine is also elevated in a dose-dependent manner, but to a lesser extent than sphinganine. The consequence of this differential inhibition is that the ratio of sphinganine to sphingosine increases, suggesting that sphinganine N-acyltransferase is the preferred target for fumonisins. Elevation of free sphinganine and free sphingosine in serum paralleled the increases in tissues. Statistically significant increases in the ratio were observed at feed concentrations as low as 5 ppm total fumonisins and in pigs (at higher concentrations) in which other serum biochemistry parameters and tissue morphology were not altered. Elevated ratios were also observed in serum from pigs fed pure fumonisin B1. The sensitivity of the ratio indicates that it could serve as an effective biomarker for consumption of fumonisin-containing feeds. In addition, the data supports the hypothesis that inhibition of sphingosine and sphinganine N-acyltransferase plays an important role in the pathogenesis of animal diseases associated with consumption of feed containing fumonisins.",
author = "Riley, {Ronald T.} and An, {Nyeon Hyoung} and Showker, {Jency L.} and Yoo, {Hwan Soo} and Norred, {William P.} and Chamberlain, {William J.} and Elaine Wang and Merrill, {Alfred H.} and Gideon Motelin and Beasley, {Val Richard} and Haschek, {Wand M.}",
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Riley, RT, An, NH, Showker, JL, Yoo, HS, Norred, WP, Chamberlain, WJ, Wang, E, Merrill, AH, Motelin, G, Beasley, VR & Haschek, WM 1993, 'Alteration of tissue and serum sphinganine to sphingosine ratio: An early biomarker of exposure to fumonisin-containing feeds in pigs', Toxicology and Applied Pharmacology, vol. 118, no. 1, pp. 105-112. https://doi.org/10.1006/taap.1993.1015

Alteration of tissue and serum sphinganine to sphingosine ratio : An early biomarker of exposure to fumonisin-containing feeds in pigs. / Riley, Ronald T.; An, Nyeon Hyoung; Showker, Jency L.; Yoo, Hwan Soo; Norred, William P.; Chamberlain, William J.; Wang, Elaine; Merrill, Alfred H.; Motelin, Gideon; Beasley, Val Richard; Haschek, Wand M.

In: Toxicology and Applied Pharmacology, Vol. 118, No. 1, 01.01.1993, p. 105-112.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Alteration of tissue and serum sphinganine to sphingosine ratio

T2 - An early biomarker of exposure to fumonisin-containing feeds in pigs

AU - Riley, Ronald T.

AU - An, Nyeon Hyoung

AU - Showker, Jency L.

AU - Yoo, Hwan Soo

AU - Norred, William P.

AU - Chamberlain, William J.

AU - Wang, Elaine

AU - Merrill, Alfred H.

AU - Motelin, Gideon

AU - Beasley, Val Richard

AU - Haschek, Wand M.

PY - 1993/1/1

Y1 - 1993/1/1

N2 - Fumonisins are a group of naturally occurring compounds produced by the fungus Fusarium moniliforme. They are believed to be the etiologic agent of several animal diseases associated with consumption of corn-based feeds including porcine pulmonary edema. Recently it was shown in vitro that fumonisins are specific inhibitors of sphingosine and sphinganine N-acyltransferases. Inhibition of these enzymes in cultured cells results in the accumulation of free long chain sphingoid bases, specifically sphingosine and sphinganine, and the depletion of complex sphingolipids. In this study, tissues and serum from male SPF pigs fed a nutritionally balanced diet containing corn or corn screenings naturally contaminated with fumonisins for up to 14 days were analyzed for free sphingoid bases and complex sphingolipids. Total fumonisins (B1 and B2) in the diets were analyzed at 0 (<1), 5, 23, 39, 101, and 175 ppm. Pulmonary edema only occurred at 175 ppm, while histologic liver damage was present at ≥23 ppm, and serum liver enzymes were significantly elevated at ≥ 101 ppm. The results of this study show that free sphinganine is elevated in liver, lung, and kidney, from pigs consuming feeds containing fumonisins at total fumonisin concentrations of 23 ppm or greater. Sphingosine is also elevated in a dose-dependent manner, but to a lesser extent than sphinganine. The consequence of this differential inhibition is that the ratio of sphinganine to sphingosine increases, suggesting that sphinganine N-acyltransferase is the preferred target for fumonisins. Elevation of free sphinganine and free sphingosine in serum paralleled the increases in tissues. Statistically significant increases in the ratio were observed at feed concentrations as low as 5 ppm total fumonisins and in pigs (at higher concentrations) in which other serum biochemistry parameters and tissue morphology were not altered. Elevated ratios were also observed in serum from pigs fed pure fumonisin B1. The sensitivity of the ratio indicates that it could serve as an effective biomarker for consumption of fumonisin-containing feeds. In addition, the data supports the hypothesis that inhibition of sphingosine and sphinganine N-acyltransferase plays an important role in the pathogenesis of animal diseases associated with consumption of feed containing fumonisins.

AB - Fumonisins are a group of naturally occurring compounds produced by the fungus Fusarium moniliforme. They are believed to be the etiologic agent of several animal diseases associated with consumption of corn-based feeds including porcine pulmonary edema. Recently it was shown in vitro that fumonisins are specific inhibitors of sphingosine and sphinganine N-acyltransferases. Inhibition of these enzymes in cultured cells results in the accumulation of free long chain sphingoid bases, specifically sphingosine and sphinganine, and the depletion of complex sphingolipids. In this study, tissues and serum from male SPF pigs fed a nutritionally balanced diet containing corn or corn screenings naturally contaminated with fumonisins for up to 14 days were analyzed for free sphingoid bases and complex sphingolipids. Total fumonisins (B1 and B2) in the diets were analyzed at 0 (<1), 5, 23, 39, 101, and 175 ppm. Pulmonary edema only occurred at 175 ppm, while histologic liver damage was present at ≥23 ppm, and serum liver enzymes were significantly elevated at ≥ 101 ppm. The results of this study show that free sphinganine is elevated in liver, lung, and kidney, from pigs consuming feeds containing fumonisins at total fumonisin concentrations of 23 ppm or greater. Sphingosine is also elevated in a dose-dependent manner, but to a lesser extent than sphinganine. The consequence of this differential inhibition is that the ratio of sphinganine to sphingosine increases, suggesting that sphinganine N-acyltransferase is the preferred target for fumonisins. Elevation of free sphinganine and free sphingosine in serum paralleled the increases in tissues. Statistically significant increases in the ratio were observed at feed concentrations as low as 5 ppm total fumonisins and in pigs (at higher concentrations) in which other serum biochemistry parameters and tissue morphology were not altered. Elevated ratios were also observed in serum from pigs fed pure fumonisin B1. The sensitivity of the ratio indicates that it could serve as an effective biomarker for consumption of fumonisin-containing feeds. In addition, the data supports the hypothesis that inhibition of sphingosine and sphinganine N-acyltransferase plays an important role in the pathogenesis of animal diseases associated with consumption of feed containing fumonisins.

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