Validation of fumonisin biornarkers in F344 rats

Fumonisins (FNs) are ubiquitous contaminants of cereal grains. Fumonisin B, (FBI) was linked to several animal and human diseases. To validate FBI biomarkers for studying human disease risks, F344 rats were administered by gavage with either a single dose of 0, 10 or 25 mgFB(1)/kg body weight (BW) or repeated doses of 0, 1.0, or 2.5 mg FB1/kg BW/day for 5 weeks. FB1 excretion and FB1-induced metabolic alterations of sphingolipids in rat urine, feces and serum were assessed. Dose-dependent urinary and fecal excretion of free FBI were found in both single-dose and repeat-dose-treated rats. In the single-dose study, urinary sphinganine (Sa) to sphingosine (So) ratio (Sa/So) reached a maximum at day 7 for the high-dose group and at day 5 for the low-dose group, whereas serum Sa/So showed only marginal changes. In the repeat-dose study, urinary Sa/So was persistently elevated at 2 weeks, while serum Sa/So was unchanged. Time course changes of sphinganine 1-phosphate (SaP) and sphingosine 1-phosphate (SoP) were also examined. Although serum Sa/So and SaP/SoP ratios showed no signs of time- or dose-dependent changes, a 10-fold increase in urinary SaP/SoP was observed, suggesting that urinary SaP/SoP is a more sensitive biomarker for FB1 exposure. The accumulation of SaP and SoP was evident in the time course of SaP/Sa and SoP/So, which may reflect activity changes of enzymes closely related to the metabolism and catabolism of SaP and SoP. These results provide concrete evidence towards the practical use of excreted FBI, Sa/So and SaP/SoP as biomarkers of exposure to FNs. (c) 2007 Elsevier Inc. All rights reserved.