Aflatoxin B1 alters central and systemic tryptophan and tyrosine metabolism: influence of immunomodulatory drugs.
Semi-chronic exposure of ICR male Mice to Aflatoxin B1 (AFB1) in non-toxic doses results in elevated lung tryptophan (TRP) levels without change in serotonin (5-HT) or 5-hydroxyindole-3-acetic acid (5-HIAA) levels. This change is organ specific in that TRP levels are not altered in spleen, duodenum, heart or central nervous system (CNS). Acute (48 hour) flunixin treatment decreases lung TRP levels and reverses the AFB1 mediated increase in lung TRP levels. On the other hand, flunixin treatment decreases CNS TRP levels in control mice but not in AFB1 treated mice. Aflatoxin B1 treated mice have an increase in splenic serotonin (5-HT) content. Acute (48 hour) treatment of mice with E. coli lipopolysaccharide (LPS) also increases splenic 5-HT, and AFB1 treatment followed by LPS have a slightly additive effect on spleen 5-HT content. Treatment of mice with LPS increases heart 5-HT, an effect which is not altered in AFB1 pretreated mice. Both LPS and AFB1 per se increases lung TYR levels although the combination of treatments is not significantly different from the control value. Flunixin treatment increases lung tyrosine (TYR) levels, an effect which is not altered by AFB1 pretreatment. Acute treatment with either LPS or flunixin decreases the CNS TRP/TYR ratio; pretreatment with AFB1 prevents those changes in the CNS TRP/TYR ratio. Central nervous system catecholamines are reduced in AFB1 pretreated mice. However, CNS catecholamine changes in AFB1 treated mice are normalized by vitamin E supplementation during the treatment period.
Weekley
L B
LB
Department of Biomedical Sciences, College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg 24061.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002273:Carcinogens; D003002:Clonixin / Q000031:analogs & derivatives / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000378:metabolism; D009928:Organ Specificity; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D014810:Vitamin E / Q000494:pharmacology
D000348:Aflatoxins; D002273:Carcinogens; D008070:Lipopolysaccharides; D014810:Vitamin E; C014557:flunixin; D014443:Tyrosine; D014364:Tryptophan; D016604:Aflatoxin B1; D003002:Clonixin