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多卤代联苯和苯巴比妥:作为羊头鲷(Archosargus probatocephalus)药物代谢酶诱导剂的评估

Polyhalogenated biphenyls and phenobarbital: evaluation as inducers of drug metabolizing enzymes in the sheepshead, Archosargus probatocephalus.

作者信息

James M O, Little P J

出版信息

Chem Biol Interact. 1981 Aug;36(2):229-48. doi: 10.1016/0009-2797(81)90022-3.

DOI:10.1016/0009-2797(81)90022-3
PMID:6268313
Abstract

Several doses of Aroclor 1254 (polychlorinated biphenyl (PCB) mixture), Firemaster FF1 (polybrominated biphenyl (PBB) mixture), 2,2',4,4',5,5'-hexabromobiphenyl (HBB), 3,3',4,4',5,5'-hexachlorobiphenyl (HCB) and phenobarbital (PB) were administered to the marine fish sheepshead (Archosargus probatocephalus). The PCB and PBB mixtures caused induction of hepatic microsomal benzo[a]pyrene hydroxylase (AHH), 7-ethoxycoumarin O-deethylase (7-EC) and 7-ethoxyresorufin O-deethylase (ERF) activities, but not benzphetamine N-demethylase (BND), epoxide hydrolase (EH) or glutathione S-transferase (GSH-T) activities. This induction pattern is typical of that caused by polycyclic aromatic hydrocarbons (PAH) in fish and mammals or by tetrachlorodibenzo-p-dioxin (TCDD) in mammals. The extent of induction of AHH-activity and cytochrome P-450 content was higher when experiments were carried out in summer (water temperature 25 +/- 4 degrees C) than in winter (water temperature 11 +/- 3 degrees C). Firemaster FF1 (15 mg/kg) induced fish for at least 56 days in both summer and winter at which time the liver concentrations of PBB were in the ppm range. PCB concentrations in the ppm range have been found in fish from polluted lakes and seas, thus we may expect that environmental exposure to PCB is sufficient to induce hepatic mixed function oxidase (MFO) activities. The PCB isomer 3,3'4,4'5,5'-HCB, which induces the same spectrum of hepatic drug-metabolizing activities as TCDD and PAH in rats, had a broadly similar effect in the sheepshead. Another purified isomer, 2,2',4,4',5,5'-HBB, which induces the same enzymes as PB in rats, had no effect on drug-metabolizing activities in sheepshead. PB was also without effect on sheepshead hepatic drug-metabolizing enzymes, although a typical narcotic effect was produced in PB-treated sheepshead. Our studies provide further evidence that drug-metabolizing activities in fish liver are readily induced by chemicals like TCDD or PAH, but we fail to demonstrate induction after treatment of sheepshead with inducers of the PB type.

摘要

向海洋鱼类羊头鲷(Archosargus probatocephalus)投喂了几剂Aroclor 1254(多氯联苯(PCB)混合物)、Firemaster FF1(多溴联苯(PBB)混合物)、2,2',4,4',5,5'-六溴联苯(HBB)、3,3',4,4',5,5'-六氯联苯(HCB)和苯巴比妥(PB)。PCB和PBB混合物可诱导肝微粒体苯并[a]芘羟化酶(AHH)、7-乙氧基香豆素O-脱乙基酶(7-EC)和7-乙氧基试卤灵O-脱乙基酶(ERF)的活性,但不诱导苄非他明N-脱甲基酶(BND)、环氧化物水解酶(EH)或谷胱甘肽S-转移酶(GSH-T)的活性。这种诱导模式是鱼类和哺乳动物中多环芳烃(PAH)或哺乳动物中四氯二苯并对二恶英(TCDD)所引起的典型模式。当在夏季(水温25±4℃)进行实验时,AHH活性和细胞色素P-450含量的诱导程度高于冬季(水温11±3℃)。Firemaster FF1(15毫克/千克)在夏季和冬季均可诱导鱼类至少56天,此时肝脏中PBB的浓度处于ppm范围。在受污染湖泊和海洋的鱼类中已发现ppm范围内的PCB浓度,因此我们可以预期环境中接触PCB足以诱导肝混合功能氧化酶(MFO)的活性。PCB异构体3,3'4,4'5,5'-HCB在大鼠中诱导的肝脏药物代谢活性谱与TCDD和PAH相同,在羊头鲷中也有大致相似的作用。另一种纯化的异构体2,2',4,4',5,5'-HBB在大鼠中诱导的酶与PB相同,但对羊头鲷的药物代谢活性没有影响。PB对羊头鲷肝脏药物代谢酶也没有影响,尽管在经PB处理的羊头鲷中产生了典型的麻醉作用。我们的研究进一步证明,鱼肝中的药物代谢活性很容易被TCDD或PAH等化学物质诱导,但在用PB类诱导剂处理羊头鲷后未能证明有诱导作用。

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