Document Detail

Dioxin-induced perturbations in tryptophan homeostasis in laboratory animals.
MedLine Citation:
PMID:  10721086     Owner:  NLM     Status:  MEDLINE    
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.
M Unkila; R Pohjanvirta; J Tuomisto
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Advances in experimental medicine and biology     Volume:  467     ISSN:  0065-2598     ISO Abbreviation:  Adv. Exp. Med. Biol.     Publication Date:  1999  
Date Detail:
Created Date:  2000-05-09     Completed Date:  2000-05-09     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  0121103     Medline TA:  Adv Exp Med Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  433-42     Citation Subset:  IM    
University of Kuopio, Department of Pharmacology and Toxicology, Finland.
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MeSH Terms
Animals, Laboratory
Body Weight / drug effects
Brain / drug effects,  metabolism*
Dioxins / pharmacology*
Homeostasis / drug effects
Hydroxyindoleacetic Acid / metabolism
Rats, Long-Evans
Rats, Wistar
Serotonin / metabolism
Tetrachlorodibenzodioxin / toxicity*
Tryptophan / metabolism*
Reg. No./Substance:
0/Dioxins; 1746-01-6/Tetrachlorodibenzodioxin; 50-67-9/Serotonin; 54-16-0/Hydroxyindoleacetic Acid; 73-22-3/Tryptophan

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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