Effect of T-2 toxin on blood-brain barrier permeability monoamine oxidase activity and protein synthesis in rats.
Systemic exposure to T-2 toxin disrupts brain biogenic monoamine metabolism. Although the mechanisms underlying these neurochemical perturbations are unclear, we have suggested that they are a reflection of increased blood-brain barrier (BBB) permeability, or altered protein synthesis that affects brain enzyme activities. Accordingly, BBB permeability, in vitro protein synthesis and in vitro monoamine oxidase (MAO) activity were examined in rats after either acute, or 7-day exposure to T-2. Membrane permeability was assessed from the recovery of systemically administered [14C]mannitol and [14C]dextran with [3H]water as the diffusible reference, either 2 hr post-intraperitoneal (i.p.) injections of 0, 0.2 and 1 mg T-2/kg body weight or following a 7-day exposure to diets containing 0 and 10 ppm T-2. Protein synthesis, determined by [14C]leucine incorporation, and MAO activity, determined by H2O2 production, were observed either 2 hr post-ip injection of 0 and 1 mg T-2/kg body weight or following a 7-day exposure to diets containing 0, 2.5 and 10 ppm T-2. Permeability increases were observed in all brain regions examined for mannitol, but not for dextran following T-2 i.p. The effect of dietary T-2 was more modest, affecting mannitol uptake in two brain regions, the cerebellum and pons plus medulla regions. Protein synthesis was significantly decreased by i.p. administration of T-2, while dietary treatment significantly reduced MAO enzyme activity. Collectively, the effect of T-2 toxin on BBB permeability, protein synthesis and MAO enzyme activity may account for the neurochemical imbalance observed in T-2 intoxication.
Department of Foods and Nutrition, University of Manitoba, Winnipeg, Canada.
J
J
Wang
D W
DW
Fitzpatrick
J R
JR
Wilson
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002250:Carbon Radioisotopes; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D003911:Dextrans; D004058:Diffusion; D006861:Hydrogen Peroxide / Q000032:analysis / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007930:Leucine; D008297:Male; D008353:Mannitol / Q000378:metabolism; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism*; D011149:Pons / Q000187:drug effects* / Q000378:metabolism; D014176:Protein Biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013605:T-2 Toxin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D014316:Tritium
D015306:Biogenic Monoamines; D002250:Carbon Radioisotopes; D003911:Dextrans; D014316:Tritium; D008353:Mannitol; D006861:Hydrogen Peroxide; D008995:Monoamine Oxidase; D007930:Leucine; D013605:T-2 Toxin