Effects of fumonisin B1 treatment on blood-brain barrier transfer in developing rats.
Fumonisin B1 (FB1), a toxic metabolite of the fungus Fusarium moniliforme found in contaminated corn, is considered an etiologic agent of equine leukoencephalomalacia. Because FB1 exposure is associated with alteration of sphingolipid metabolism, the purpose of this study was to elucidate whether blood sphinganine (Sa) levels affect brain Sa levels. Sa and sphingosine (So) levels in brain tissue and plasma were analyzed by HPLC. Area under the curve (AUC0-20h) ratios of brain Sa to plasma Sa levels were about 40 after a single 0.8 or 8 mg/kg SC dose of FB1. The AUC0-12h ratio of brain FB1 to plasma FB1 was 0.02. The fact that FB1 alters brain Sa levels and Sa/So ratios indicates that sphingolipid metabolism in the central nervous system of developing rats is vulnerable to FB1 exposure. These data support our hypothesis that alterations of the brain Sa levels are related to the direct action of FB1 on the brain rather than transport of peripheral Sa to the brain.
Kwon
O S
OS
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Sandberg
J A
JA
Slikker
W
W
D000818:Animals; D019540:Area Under Curve; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D002264:Carboxylic Acids / Q000097:blood / Q000633:toxicity*; D002274:Carcinogens, Environmental / Q000032:analysis / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D037341:Fumonisins; D008297:Male; D011247:Pregnancy; D016548:Prosencephalon / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
D002264:Carboxylic Acids; D002274:Carcinogens, Environmental; D037341:Fumonisins; C056933:fumonisin B1; D013110:Sphingosine; C005682:safingol