Validation of fumonisin biomarkers in F344 rats.
Fumonisins (FNs) are ubiquitous contaminants of cereal grains. Fumonisin B(1) (FB(1)) was linked to several animal and human diseases. To validate FB(1) biomarkers for studying human disease risks, F344 rats were administered by gavage with either a single dose of 0, 10 or 25 mg FB(1)/kg body weight (BW) or repeated doses of 0, 1.0, or 2.5 mg FB(1)/kg BW/day for 5 weeks. FB(1) excretion and FB(1)-induced metabolic alterations of sphingolipids in rat urine, feces and serum were assessed. Dose-dependent urinary and fecal excretion of free FB(1) 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 FB(1) 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 FB(1), Sa/So and SaP/SoP as biomarkers of exposure to FNs.
Cai
Qingsong
Q
Department of Environmental Toxicology, The Institute of Environmental and Human Health, Box 41163, Texas Tech University, Lubbock, TX 79409-1163, USA.
Tang
Lili
L
Wang
Jia-Sheng
JS
D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002274:Carcinogens, Environmental / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005506:Food Contamination; D037341:Fumonisins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D009183:Mycotoxins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D013110:Sphingosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D013997:Time Factors
D015415:Biomarkers; D002274:Carcinogens, Environmental; D037341:Fumonisins; D008246:Lysophospholipids; D009183:Mycotoxins; C060504:dihydrosphingosine 1-phosphate; C060506:sphingosine 1-phosphate; C056933:fumonisin B1; D013110:Sphingosine; C005682:safingol