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The induction and persistence of altered sphingolipid biosynthesis in rats treated with fumonisin B1
L Garren1, D Galendo, C P Wild
1Unit of Gene-Environment Interactions, International Agency for Research on Cancer, Lyon, France.
Abstract:
The fumonisins produced by Fusarium spp. are carcinogenic in rodents and possibly carcinogenic to humans. One action of fumonisins is to inhibit the enzyme ceramide synthase and as a consequence disrupt de novo sphingolipid biosynthesis. Measurement of the ratio of sphinganine (Sa) to sphingosine (So) in urine, serum and tissues has thus been made in various animal species as a marker of exposure to this mycotoxin. In this study in male BDIV rats, the effect of increasing daily gavage doses (0.01-5 mg/kg b.w.) of fumonisin B1 (FB1) on the Sa/So ratio in various tissues and urine was examined as was the persistence of the effects after cessation of treatment. The lowest dose of FB1 which induced an alteration of Sa/So in any tissue was 1 mg/kg b.w. The tissue most affected was the kidney, with the liver affected to a much lesser extent and the lung and oesophagus not at all. Only a modest indication of an alteration in Sa/So ratio was obtained in the urine. The large interindividual variations in urinary Sa and So in this strain of rat, even in the absence of FB1 treatment, made interpretation of these data difficult. After cessation of treatment, the Sa/So ratio returned to normal in kidney after a period of 1-3 weeks. These data suggest that altered Sa/So ratios reflect recent exposure to FB1 in the rat.
Insights
Fumonisin B1 exposure in rats alters the sphinganine (Sa) to sphingosine (So) ratio, particularly in kidneys. This ratio returns to normal within weeks after exposure stops, indicating recent fumonisin B1 intake.
Area of Science:
- Toxicology
- Biochemistry
- Mycotoxicology
Background:
- Fumonisins, produced by Fusarium species, are carcinogenic and inhibit ceramide synthase, disrupting sphingolipid biosynthesis.
- The sphinganine (Sa) to sphingosine (So) ratio is used as a biomarker for fumonisin exposure.
- Understanding the dose-response and persistence of these effects is crucial for risk assessment.
Purpose of the Study:
- To investigate the effect of varying fumonisin B1 (FB1) doses on the Sa/So ratio in male BDIV rats.
- To determine the persistence of FB1-induced alterations in the Sa/So ratio after treatment cessation.
Main Methods:
- Male BDIV rats were gavaged with daily doses of FB1 ranging from 0.01 to 5 mg/kg body weight.
- The Sa/So ratio was measured in various tissues (kidney, liver, lung, oesophagus) and urine.
- Tissue and urine samples were analyzed post-treatment to assess the duration of altered Sa/So ratios.
Main Results:
- The lowest effective dose of FB1 altering the Sa/So ratio was 1 mg/kg body weight.
- Kidneys showed the most significant alterations, followed by the liver; lungs and oesophagus were unaffected.
- Urinary Sa/So ratio changes were modest and difficult to interpret due to high interindividual variability.
- Altered Sa/So ratios in the kidney normalized within 1-3 weeks after FB1 treatment stopped.
Conclusions:
- Altered Sa/So ratios serve as a sensitive indicator of recent fumonisin B1 exposure in rats.
- Kidney tissue is a primary target for FB1 toxicity, reflected by changes in the Sa/So ratio.
- The reversibility of the Sa/So ratio suggests its utility in monitoring exposure cessation.
