Fumonisin B1 in developing rats alters brain sphinganine levels and myelination.
Objectives of this study were to test the hypothesis that fumonisin B1 (FB1) alters sphinganine (Sa) levels and myelin synthesis in the central nervous system of developing rats. FB1 (subcutaneous, 0.4 or 0.8 mg/kg/day) from postnatal days (PND) 3 to PND 12 resulted in a significant reduction of body weight gain and decreased survival rates. Both Sa levels and Sa/sphingosine (So) ratios were significantly increased in the brain of rats given 0.8 mg FB1/kg/day. To confirm the effect of limited nutrition on changes in the Sa levels and myelinogenesis, rats given 0.8 mg FB1/kg/day or treated by limited nutrition (temporary removal from dam during postnatal period) were compared to those in saline controls. Sa levels and Sa/So ratios were increased significantly in the 0.8 FB1-treated, but were not altered in the limited nutrition group. Myelin deposition in the corpus callosum and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) activities were decreased significantly in both nutritionally limited and FB1-exposed rats. These data indicate that sphingolipid metabolism in the central nervous system of developing rats is vulnerable to FB1 exposure. The hypomyelination associated with FB1-treatment may be mediated by limited nutrition.
Kwon
O S
OS
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Schmued
L C
LC
Slikker
W
W
D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development*; D001923:Brain Chemistry / Q000187:drug effects*; D002264:Carboxylic Acids / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005260:Female; D037341:Fumonisins; D006651:Histocytochemistry; D009183:Mycotoxins / Q000633:toxicity*; D009186:Myelin Sheath / Q000187:drug effects*; D011247:Pregnancy; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D037341:Fumonisins; D009183:Mycotoxins; C056933:fumonisin B1; D011493:Protein Kinase C; D013110:Sphingosine; C005682:safingol