The effect of 3,4,3',4'-tetrachlorobiphenyl on plasma retinol and hepatic retinyl palmitate hydrolase activity in female Sprague-Dawley rats.

The Effect of 3,4,3',4'-Tetrachlorobiphenyl on Plasma Retinol and Hepatic Retinyl Palmitate Hydrolase Activity in Female Sprague-Dawley Rats. Powers, R.H., Gilbert, L.C., and Aust, S.D. (1987). Toxicol Appl. Pharmacol. 89, 370-377. A single ip dose of 1, 5, or 15 mg/kg 3,4,3',4'-tetrachlorobiphenyl (TCB) caused a dose-dependent depression of plasma retinol levels 24 hr after treatment of female Sprague-Dawley rats. The loss of plasma retinol appeared to be a function of depressed levels of the retinol-retinol-binding protein (RBP)-transthyretin ternary complex. No free retinol-RBP was observed in plasma from treated animals. Hepatic retinyl palmitate hydrolase (RPH) activity was also depressed and highly and positively correlated to the plasma retinol levels. TCB was determined to be a noncompetitive inhibitor of partially purified RPH with a KI of 91 microM. Incubation of TCB with liver microsomes and NADPH decreased the inhibition of RPH. Doses of either 2,4,5,2',4',5'-hexachlorobiphenyl (HCB) or 3,4,5,3',4',5'-HCB equimolar to the 15 mg/kg TCB dose failed to cause a similar depression of plasma retinol in treated female rats. We conclude that, unlike other polychlorinated biphenyl congeners, TCB causes a depression of plasma retinol by inhibition of hepatic RPH.