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 withE. 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 AFB₁per 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 catecho lamine changes in AFB₁ treated mice are normalized by vitamin E supplementation during the treatment period.