Effects of halogenated dibenzo-p-dioxins on plasma disappearance and biliary excretion of ouabain in rats☆

Add time:08/18/2019    Source:sciencedirect.com

A single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7-tribromodibenzo-p-dioxin (2,3,7-TBDD), 1,2,3,7,8,9-hexachlorodibenzo-p-dioxin (1,2,3,7,8,9-HCDD), 1,2,4,6,7,9-hexachlorodibenzo-p-dioxin (1,2,4,6,7,9-HCDD), or 1,3,6,8-tetrachlorodibenzo-p-dioxin (1,3,6,8-TCDD) was given to male rats (25 μgkg, p.o.) and plasma concentration and biliary excretion of ouabain assessed 10 days later. Treatment of TCDD, 2,3,7-TBDD and to a lesser extent 1,2,3,7,8,9-HCDD increased the plasma concentration of ouabain and decreased its excretion into bile. Two other compounds 1,2,4,6,7,9-HCDD and 1,3,6,8-TCDD had no effect on biliary excretion of ouabain. TCDD, 2,3,7-TBDD and to a lesser extent, 1,2,3,7,8,9-HCDD decreased the bile flow. Liver wet weight was increased in TCDD and 2,3,7-TBDD treated rats. The magnitude of depression in ouabain excretion by those compounds was closely related to the reported relative binding affinity of the compound to liver cytosol and their induction potency of aryl hydrocarbon hydroxylase activity.

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