4-氨基联苯在大鼠体内的代谢。IV. 4-氨基联苯代谢产物形成高铁血红蛋白的过程。

The metabolism of 4-aminobiphenyl in rat. IV. Ferrihaemoglobin formation by 4-aminobiphenyl metabolites.

Karreth S, Lenk W

Walther Straub-Institut für Pharmakologie und Toxikologie, LM-Universität München, Germany.

Xenobiotica. 1991 Jul;21(7):971-7. doi: 10.3109/00498259109039536.

Abstract

Rats dosed with nitrosobenzene (56 mumol/kg), 4-chloronitrosobenzene (53 mumol/kg), 3,4-dichloronitrosobenzene (53 mumol/kg), 4-ethoxynitrosobenzene (86 mumol/kg), 4-nitrosobiphenyl(nitroso-BP, 55 mumol/kg) or 2-nitrosofluorene (256 mumol/kg) had maximal ferrihaemoglobin (HbFe3+) concn of 69, 68, 69, 67, 55 and 42% after 15, 25, 48, 35, 80 and 115 min, respectively, indicating differences in solubility of the nitrosoarenes in body fluids. 2. Nitroso-BP and 3-hydroxy-4-aminobiphenyl (3-hydroxy-ABP) catalytically oxidized HbFe2+ in bovine erythrocytes in vitro; nitroso-BP was three times as active as 3-hydroxy-ABP. 3',4'-Dihydroxy-4-aminobiphenyl (3',4'dihydroxy-ABP) showed only low catalytic activity, and seven other ABP metabolites exhibited only marginal activity. 3. Nitroso-BP was inactive in solutions of purified human Hb, but 3-hydroxy-ABP catalytically oxidized HbFe2+, indicating that nitrosoarenes oxidize HbFe2+ in erythrocytes in vitro and in vivo by a mechanism different from that of o-aminophenols. The second-order rate constant for HbFe2+ oxidation by 3-hydroxy-ABP at 37 degrees C was k2 = 19.1 +/- 1.31/mol per s.

摘要

给大鼠分别注射亚硝基苯（56微摩尔/千克）、4-氯亚硝基苯（53微摩尔/千克）、3,4-二氯亚硝基苯（53微摩尔/千克）、4-乙氧基亚硝基苯（86微摩尔/千克）、4-亚硝基联苯（亚硝基-BP，55微摩尔/千克）或2-亚硝基芴（256微摩尔/千克）后，分别在15、25、48、35、80和115分钟时，高铁血红蛋白（HbFe3+）的最大浓度分别为69%、68%、69%、67%、55%和42%，这表明亚硝基芳烃在体液中的溶解度存在差异。2. 亚硝基-BP和3-羟基-4-氨基联苯（3-羟基-ABP）在体外能催化氧化牛红细胞中的HbFe2+；亚硝基-BP的活性是3-羟基-ABP的三倍。3',4'-二羟基-4-氨基联苯（3',4'-二羟基-ABP）仅表现出较低的催化活性，其他七种ABP代谢产物仅表现出微弱活性。3. 亚硝基-BP在纯化的人血红蛋白溶液中无活性，但3-羟基-ABP能催化氧化HbFe2+，这表明亚硝基芳烃在体外和体内通过与邻氨基酚不同的机制氧化红细胞中的HbFe2+。37℃时，3-羟基-ABP氧化HbFe2+的二级反应速率常数为k2 = 19.1±1.3升/摩尔·秒。