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A blood spot method for detecting fumonisin-induced changes in putative sphingolipid biomarkers in LM/Bc mice and humans

Author:
Riley, Ronald T., Showker, Jency L., Lee, Christine M., Zipperer, Cody E., Mitchell, Trevor R., Voss, Kenneth A., Zitomer, Nicholas C., Torres, Olga, Matute, Jorge, Gregory, Simon G., Ashley-Koch, Allison E., Maddox, Joyce R., Gardner, Nicole, Gelineau-Van Waes, Janee B.
Source:
Food additives & contaminants 2015 v.32 no.6 pp. 934-949
ISSN:
1944-0057
Subject:
absorbance, animal models, biomarkers, blood, blood volume, ceramides, corn, formic acid, fumonisins, half life, humans, males, mice, neural tube defects, paper, protein content, risk factors, tissues, urine
Abstract:
Fumonisins (FB) are mycotoxins found in maize. They are hypothesised risk factors for neural tube defects (NTDs) in humans living where maize is a dietary staple. In LM/Bc mice, FB ₁-treatment of pregnant dams induces NTDs and results in increased levels of sphingoid base 1-phosphates in blood and tissues. The increased level of sphingoid base 1-phosphates in blood is a putative biomarker for FB ₁ inhibition of ceramide synthase in humans. Collection of blood spots on paper from finger sticks is a relatively non-invasive way to obtain blood for biomarker analysis. The objective of this study was to develop and validate in an animal model, and ultimately in humans, a method to estimate the volume of blood collected as blood spots on absorbent paper so as to allow quantification of the molar concentration of sphingoid base 1-phosphates in blood. To accomplish this objective, blood was collected from unexposed male LM/Bc and FB ₁-exposed pregnant LM/Bc mice and humans and applied to two types of absorbent paper. The sphingoid base 1-phosphates, absorbance at 270 nm (A ₂₇₀), and total protein content (Bradford) were determined in the acetonitrile:water 5% formic acid extracts from the dried blood spots. The results show that in both mouse and human the A ₂₇₀, total protein, and blood volume were closely correlated and the volume of blood spotted was accurately estimated using only the A ₂₇₀ of the extracts. In mouse blood spots, as in tissues and embryos, the FB ₁-induced changes in sphingolipids were correlated with urinary FB ₁. The half-life of FB ₁ in the urine was short (<24 h) and the elevation in sphingoid base 1-phosphates in blood was also short, although more persistent than the urinary FB ₁.
Agid:
1328508