Abstract
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. 10μg/kg) and Han/Wistar (H/W, Kuopio; LD50 over 10,000 μg/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.
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Unkila, M., Pohjanvirta, R., Tuomisto, J. (1999). Dioxin-Induced Perturbations in Tryptophan Homeostasis in Laboratory Animals. In: Huether, G., Kochen, W., Simat, T.J., Steinhart, H. (eds) Tryptophan, Serotonin, and Melatonin. Advances in Experimental Medicine and Biology, vol 467. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4709-9_55
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