Dioxin-induced perturbations in tryptophan homeostasis in laboratory animals.
Polychlorinated dioxins (PCDD) are widespread environmental contaminants. The most potent and the general model compound for dioxins is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Our laboratory has developed a new model for studies of dioxin toxicity based on totally disparate sensitivity to the lethal action of TCDD between Long-Evans (L-E, Turku AB; LD50 ca. 10 micrograms/kg) and Han/Wistar (H/W, Kuopio; LD50 over 10,000 micrograms/kg) rat strains. We have shown that body weight regulation is differentially regulated by TCDD in these rat strains: body weight gain is permanently reduced in the sensitive L-E but not in the resistant H/W strain. In concert with reduced body weight, TCDD increased brain TRP concentration, 5-HT synthesis and its metabolism to 5-HIAA at lethal doses in TCDD-susceptible L-E rats, and almost not at all in resistant H/W rats in which lethal dose levels were not reached. Further studies showed that TCDD indirectly increases free TRP concentration in the circulation in TCDD-susceptible L-E rats. Blood free fatty acids seem to be involved in the latter phenomenon. It is not likely that the enhanced serotonergic tone in the CNS is a causative factor in TCDD-induced anorexia. However, the present results may open up an interesting avenue to better understand physiology of TRP and the complex regulation of energy balance.
Unkila
M
M
University of Kuopio, Department of Pharmacology and Toxicology, Finland. mtu@po.cwru.edu
Pohjanvirta
R
R
Tuomisto
J
J
D000818:Animals; D000830:Animals, Laboratory; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004147:Dioxins / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism*
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan