Alterations in plasma tryptophan binding to albumin in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated Long-Evans rats.
We have previously shown that the wasting syndrome in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) administration is associated with a specific increase in free tryptophan (unbound to albumin) in rats. The present series of experiments was undertaken to characterize how the binding of tryptophan to albumin is altered by TCDD and to find the underlying cause of the changes. TCDD administered to Long-Evans rats proved to diminish the maximal binding capacity (Bmax) of albumin for tryptophan by ca. 60% without any marked change in the binding affinity. Of candidate mediating factors, neither TCDD nor bilirubin affected the binding equilibrium of tryptophan with albumin in vitro. However, a mixture of free fatty acids greatly increased the proportion of free tryptophan at physiologically relevant concentrations. Similarly, the free fatty acid mixture added to plasma in vitro decreased only Bmax of albumin in a manner similar to the effect of TCDD administered in vivo. Extraction of lipid-soluble substances from the plasma with ether was effective in reversing the increase in free tryptophan in the plasma of TCDD-treated rats while dialysis of water-soluble substances was not. Ether extraction also resulted in a decrease in free fatty acids. We conclude that disturbances in lipid metabolism may be involved in the pathogenesis of TCDD-induced alterations in tryptophan binding to albumin in vivo.
Unkila
M
M
National Public Health Institute, Department of Toxicology, Kuopio, Finland.
Pohjanvirta
R
R
Tuomisto
J T
JT
Tuomisto
J
J
D000818:Animals; D001663:Bilirubin / Q000378:metabolism; D003956:Dialysis; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D007700:Kinetics; D008024:Ligands; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011485:Protein Binding; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism*; D014364:Tryptophan / Q000097:blood*
D005230:Fatty Acids, Nonesterified; D008024:Ligands; D000072317:Polychlorinated Dibenzodioxins; D012709:Serum Albumin; D014364:Tryptophan; D001663:Bilirubin