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 wi th 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 t he underlying cause of the changes. TCDD administered to Long-Evans ra ts proved to diminish the maximal binding capacity (B-max) of albumin for tryptophan by ca. 60% without any marked change in the binding aff inity. Of candidate mediating factors, neither TCDD nor bilirubin affe cted the binding equilibrium of tryptophan with albumin in vitro. Howe ver, 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 B-max of albumin in a manner similar to the effect of TCDD administere d in vivo. Extraction of lipid-soluble substances from the plasma with ether was effective in reversing the increase in free tryptophan in t he plasma of TCDD-treated rats while dialysis of water-soluble substan ces was not. Ether extraction also resulted in a decrease in free fatt y acids. We conclude that disturbances in lipid metabolism may be invo lved in the pathogenesis of TCDD-induced alterations in tryptophan bin ding to albumin in vivo.