Tissue distribution and proinflammatory cytokine gene expression following acute oral exposure to deoxynivalenol: comparison of weanling and adult mice.
The frequent presence of deoxynivalenol (DON) in cereal-based foods and the high intake of these foods by children raises particular concerns about the relative susceptibility of this subpopulation to adverse effects evoked by this mycotoxin. We tested the hypothesis that both toxicokinetics and proinflammatory cytokine gene expression following a oral DON exposure at 5mg/kg bw differ between weanling (3-4 wk) and young adult (8-10 wk) female mice. DON was rapidly taken up with maximum plasma concentrations reaching 1.0 microg/ml in adult mice at 15 min, whereas DON levels were approximately twice as much in weanling mice at these times. DON was rapidly cleared in both weanling and adult mice with concentrations being reduced by 78% and 81% of the peak levels, respectively, after 2h. DON accumulation and clearance in spleen, liver, lung and kidney followed similar kinetics to that of plasma with tissue burdens also reaching twice that of adult mice. When TNF-alpha, IL-1beta and IL-6 mRNAs in spleens (a primary source of systemic proinflammatory cytokines) were used as biomarkers of the DON's effects, expression of these mRNAs was two to three times greater in weanling than adult mouse. However, differences in proinflammatory cytokine expression were less robust or not apparent in the liver or lung. Taken together, these data suggest that young mice are modestly more susceptible than adult mice to the adverse effects of DON and that this might result from a greater toxin tissue burden.
Pestka
James J
JJ
Department of Food Science and Human Nutrition, 234 G.M. Trout Building, Michigan State University, East Lansing, MI 48824-1224, United States. pestka@msu.edu
Amuzie
Chidozie J
CJ
D000375:Aging / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007249:Inflammation / Q000378:metabolism*; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D009183:Mycotoxins / Q000633:toxicity*; D010599:Pharmacokinetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution; D014255:Trichothecenes / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D015415:Biomarkers; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D009183:Mycotoxins; D012333:RNA, Messenger; D014255:Trichothecenes; D014409:Tumor Necrosis Factor-alpha; C007262:deoxynivalenol