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3,4,3',4'-四氯联苯对雌性斯普拉格-道利大鼠血浆视黄醇及肝脏视黄醇棕榈酸酯水解酶活性的影响

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

作者信息

Powers R H, Gilbert L C, Aust S D

出版信息

Toxicol Appl Pharmacol. 1987 Jul;89(3):370-7. doi: 10.1016/0041-008x(87)90156-6.

DOI:10.1016/0041-008x(87)90156-6
PMID:3111014
Abstract

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.

摘要

3,4,3',4'-四氯联苯对雌性斯普拉格-道利大鼠血浆视黄醇及肝脏视黄醇棕榈酸酯水解酶活性的影响。鲍尔斯,R.H.,吉尔伯特,L.C.,及奥斯特,S.D.(1987年)。《毒理学与应用药理学》89卷,370 - 377页。对雌性斯普拉格-道利大鼠单次腹腔注射1、5或15毫克/千克的3,4,3',4'-四氯联苯(TCB)后24小时,可导致血浆视黄醇水平呈剂量依赖性降低。血浆视黄醇的减少似乎是视黄醇-视黄醇结合蛋白(RBP)-转甲状腺素蛋白三元复合物水平降低的结果。在处理过的动物血浆中未观察到游离的视黄醇-RBP。肝脏视黄醇棕榈酸酯水解酶(RPH)活性也降低,且与血浆视黄醇水平高度正相关。已确定TCB是部分纯化的RPH的非竞争性抑制剂,抑制常数(KI)为91微摩尔。TCB与肝微粒体及NADPH共同孵育可降低对RPH的抑制作用。与15毫克/千克TCB剂量等摩尔的2,4,5,2',4',5'-六氯联苯(HCB)或3,4,5,3',4',5'-六氯联苯剂量,未能使处理过的雌性大鼠血浆视黄醇出现类似降低。我们得出结论,与其他多氯联苯同系物不同,TCB通过抑制肝脏RPH导致血浆视黄醇降低。

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