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Title: TIME- AND DOSE-DEPENDENT CHANGES IN SPHINGOID BASE 1-PHOSPHATES IN TISSUES FROM RATS FED DIETS CONTAINING FUMONISINS

Author
item Riley, Ronald
item Showker, Adele
item Voss, Kenneth

Submitted to: Toxicological Sciences
Publication Type: Abstract Only
Publication Acceptance Date: 1/30/2005
Publication Date: 3/15/2005
Citation: Riley, R.T., Showker, A.J., Voss, K.A. 2005. Time- and dose-dependent changes in sphingoid base 1-phosphates in tissues from rats fed diets containing fumonisins [abstract]. Toxicological Sciences. 84(S1):284-285.

Interpretive Summary: abstract - no summary

Technical Abstract: Fumonisins (FB) are mycotoxins found in corn. They are inhibitors of ceramide synthase (CS), a key enzyme in de novo sphingolipid biosynthesis. Inhibition of CS results in a marked increase in free sphinganine (Sa), an intermediate in de novo biosynthesis, in rat liver and kidney; the primary target organs in FB fed rats. There is a close correlation between elevation in Sa and the extent and severity of toxicity in rodent liver and kidney. Sa is toxic to cultured cells and is believed to contribute to the liver and kidney toxicity of FB, however, inhibition of CS also decreases ceramide formation and potentially, increases levels of Sa-1-phosphate (Sa-1-P) and sphingosine (So)-1-phosphate (So-1-P). The present study was conducted to quantify the time- and dose dependent changes in Sa, So, Sa-1-P and So-1-P in kidney and liver of male Sprague-Dawley rats fed diets containing 0, 5 ppm and 50 ppm FB1 for 10 days. These tissues were microscopically examined for increased apoptosis and other FB-induced toxicity. At 50 ppm FB1, renal toxicity was first evident on day 3 and was maximal on day five, whereas, Sa and Sa-1-P were first elevated at day 1 and maximally elevated at day 5 to similar levels. So-1-P was first elevated on day 3 and maximally elevated on day 5, however, the level of elevation was 50 fold less than Sa-1-P. Neither So-1-P nor Sa-1-P was detected in control kidney. At 5 ppm FB1, renal toxicity was first evident on day 5 and was more severe on day 10, whereas, Sa was first elevated on day 1 and increased throughout the 10 day study. Sa-1-P and So-1-P were first elevated at days 3 and 5, respectively, and were further increased on day 10. Compared to kidney, liver toxicity was much more subtle, with an obvious but moderate effect only being seen in the high dose group on days 5 and 10 and was preceded by increases in Sa on day 3. There was no So-1-P or Sa-1-P detected in liver from control or FB1-fed animals. The high level of Sa-1-P in kidney from FB-treated rats suggests its involvement in FB-induced renal toxicity.