Elevation of sphinganine 1-phosphate as a predictive biomarker for fumonisin exposure and toxicity in mice.
Fumonisins are specific inhibitors of ceramide synthase in sphingolipid metabolism. An alteration in sphingolipid metabolism as a result of fumonisin B1 (FB1) exposure is related to cell death, and sphinganine/sphingosine ratio has been used as an indicator of fumonisin exposure in animals. The objective of this study was to investigate a new biochemical marker for the prediction of fumonisin-induced toxicity. When mice were treated with FB1 (10 mg/kg ip/d) for 5 d, the serum levels of sphingoid bases and their 1-phosphate were markedly elevated. The accumulation of sphingosine 1-phosphate (So-1-P) and sphinganine 1-phosphate (Sa-1-P) in serum following FB1 treatment was more apparent than elevated levels of sphingosine (So) and sphinganine (Sa). Sa-1-P/So-1-P ratio in serum was more elevated than Sa/So ratio following fumonisin B1 treatment, indicating that phosphorylation of sphingoid bases may be a sensitive biomarker for fumonisin exposure. In addition, the tissue levels of Sa and Sa-1-P were also significantly elevated in kidneys, liver, heart, lung and brain. FB1-induced toxicity was confirmed microscopically in both liver and kidneys. Liver lesions consisted of centrilobular hypertrophy and cytoplasmic vacuolization. In addition, hepatic binucleated cells were increased and acidophilic body was observed in FB1-treated mice. Kidney lesions were consistent with tubular nephrosis, and tubules were dilated and contained cell debris in FB1-exposed mice. These results suggested that the elevation of Sa-1-P as well as Sa in serum would be a specific biomarker for predicting FB1 exposure, and elevated tissue levels of Sa-1-P may be related to fumonisin toxicity in animals.
Kim
Dong-Hyun
DH
College of Pharmacy, Chungbuk National University, Cheongju, Korea.
Yoo
Hwan-Soo
HS
Lee
Yong-Moon
YM
Kie
Jeong-Hae
JH
Jang
Soyong
S
Oh
Seikwan
S
D000818:Animals; D015415:Biomarkers / Q000097:blood; D037341:Fumonisins / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010088:Oxidoreductases; D011237:Predictive Value of Tests; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood
D015415:Biomarkers; D037341:Fumonisins; C060504:dihydrosphingosine 1-phosphate; C056933:fumonisin B1; D010088:Oxidoreductases; C108138:dihydroceramide desaturase; D013110:Sphingosine