Antinutritional effects of fumonisin B1 and pathophysiological consequences.
Due to its structural similarity with sphingosine, fumonisin B(1) (FB(1)) inhibits ceramide synthase (a key enzyme of sphingolipid biosynthesis) leading to an intracellular accumulation of sphingoid bases with a consequent increase of sphinganine/sphingosine (SA/SO) ratio. In adult male rats, dietary exposure to fumonisin induces a significant increase in both SA concentrations and SA/SO ratio in kidney, but not in liver and brain, as well as a significant reduction of body weight gain. Regarding the brain, the developing rat is more sensitive to FB(1) than the adult rat. FB(1) treatment produces in the forebrain and brainstem: (i) an increase in SA levels and SA/SO ratio, (ii) a reduction in myelin deposition, and (iii) an impairment of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) activity. FB(1) effects on myelin are similar to those produced by starvation (temporary removal of pups from dam during postnatal period), thus suggesting that hypomyelination could be due, at least partly, to a nutritional deficiency. Finally, FB(1) reduces the uptake of folate in different cell lines. The resulting folate deficiency could explain the association of FB(1) exposure with neural tube defects.
Carratù
M R
MR
Department of Pharmacology and Human Physiology, Medical School, University of Bari, Policlinico, Piazza G. Cesare, 70124, Bari, Italy. mrc@farmacol.uniba.it
Cassano
T
T
Coluccia
A
A
Borracci
P
P
Cuomo
V
V
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004032:Diet; D005494:Folic Acid Deficiency / Q000139:chemically induced / Q000503:physiopathology; D037341:Fumonisins / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D051381:Rats; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism
D037341:Fumonisins; C092631:fumonisin A1; D010088:Oxidoreductases; C108138:dihydroceramide desaturase; D013110:Sphingosine; C005682:safingol