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United States Department of Agriculture

Agricultural Research Service

Title: Persistence and Reversibility of the Elevation in Free Sphingoid Bases Induced by Fumonisin Inhibition of Ceramide Synthase

Authors
item Enongene, E - FDA, WASHINGTON, DC
item Sharma, R - PHY/PHARM/VET MED, UGA
item Bhandari, N - PHY/PHARM/VET MED, UGA
item Miller, J - CHEM/CARLETON U,OT,CANADA
item Meredith, Filmore
item Voss, Kenneth
item Riley, Ronald

Submitted to: Toxicological Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 14, 2002
Publication Date: N/A

Interpretive Summary: Fumonisins are toxic chemicals produced by molds that contaminate US corn. The presence of fumonisin in US corn can reduce the value of the corn. The Food and Drug Administration has published guidelines for fumonisins in corn and corn products. The guidelines are based on what is known about the levels of fumonisin in food that can cause harm to animals. Because fumonisins are potentially harmful to humans and because the level at which they are harmful to animals is used as the basis for setting guidelines by CODEX, the levels which can cause harm in animals and humans must be established as accurately as possible. One way to determine if humans are affected by fumonisins is to use markers that indicate that exposure to fumonisins has occurred. One such marker is a chemical called sphinganine. Sphinganine is an unusual fat that accumulates when animals are exposed to fumonisin. The present study was designed to determine how little fumonisin could cause a change in the marker sphinganine in mice and how persistent is the change in the marker. The study found that very low exposure could prolong the time that the marker was increased after animals were exposed to high levels. The work also shows that the length of time that the marker is increased is different for different organs. This is important because in order to predict if exposure has occurred, it is necessary to know how long the marker stays elevated after the exposure is over.

Technical Abstract: These studies determined: 1) the time course for sphingoid base elevation in the small intestines, liver and kidney of mice following a single 25 mg/kg bw oral dose (high dose) of FB1, 2) the minimum threshold dose of FB1 that would prolong the elevated sphingoid base concentration in kidney following the single high dose, and 3) the importance of the balance between the rate of sphingoid base biosynthesis and degradation in the persistence of sphingoid base accumulation. Following the high dose of FB1, there was an increase in sphinganine in intestinal cells and liver that peaked at 4 to 12 h and declined to near the control level by 48 h. In kidney, sphinganine peaked at 6-12 h but remained elevated until 72 h, approaching control levels at 96-120 h. Oral administration of 0.03 mg FB1/kg bw (low dose) for 5 days had no effect on the sphingoid bases in kidney. However, following an initial high dose, daily administration of the low dose prolonged the elevation in kidney sphinganine compared to mice receiving a single high dose. Thus, a single exposure to a high dose of FB1 followed by daily exposure at low levels will prolong the elevation of sphinganine in kidney. In cultured renal cells FB1 was rapidly eliminated, but elevated sphinganine was persistent. This persistence in renal cells was rapidly reversed in the presence of ISP-1, indicating that the persistence was due to differences in the rates of sphinganine biosynthesis and degradation. The in vivo persistence in kidney may be due to similar differences.

Last Modified: 7/30/2014
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