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苄基甲苯的研究。I. 四氯苄基甲苯及其缩合物对微粒体细胞色素P-450和UDP-葡萄糖醛酸基转移酶的诱导作用。

Investigations on benzyltoluenes. I. Induction of microsomal cytochrome P-450 and UDP-glucuronosyltransferase by tetrachlorobenzyltoluenes and by the condensate.

作者信息

von Meyerinck L, Hufnagel B, Schmoldt A, Benthe H F

机构信息

Abteilung Pharmakologie für Pharmazeuten, Universitäts-Krankenhaus Eppendorf, F.R.G.

出版信息

Toxicol Lett. 1990 Apr;51(2):163-74. doi: 10.1016/0378-4274(90)90208-4.

Abstract

Tetrachlorobenzyltoluene (TCBT) (Ugilec 141) was investigated in induction experiments in male and female Wistar rats with long-term (50, 100 and 300 mg/kg p.o. daily for 28 days) and short-term administration (300 mg/kg once and 100 mg/kg daily for 4 days). The increase in total cytochrome P-450 did not exceed the factor of 1.9 compared to controls, while benzphetamine N-demethylase rose up to 3.5-fold the levels measured in controls, with very low induction of benzo(a)pyrene hydroxylase or ethoxyresorufin O-deethylase. Parallel investigations of UDP-glucuronosyltransferase showed induction of testosterone glucuronidation (1.7-fold). Administration (300 mg/kg body wt. once) of a pyrolysate of TCBT resulted in a marked increase in cytochrome P-450c dependent reactions (benzo(a)pyrene hydroxylase, ethoxyresorufin O-deethylase).

摘要

在雄性和雌性Wistar大鼠中进行了四氯苄基甲苯(TCBT)(Ugilec 141)的诱导实验,采用长期给药(每天口服50、100和300 mg/kg,持续28天)和短期给药(一次300 mg/kg以及每天100 mg/kg,持续4天)。与对照组相比,总细胞色素P-450的增加不超过1.9倍,而苄非他明N-脱甲基酶的水平升至对照组所测水平的3.5倍,苯并(a)芘羟化酶或乙氧异吩恶唑酮O-脱乙基酶的诱导作用非常低。对尿苷二磷酸葡萄糖醛酸基转移酶的平行研究显示睾酮葡萄糖醛酸化有诱导作用(1.7倍)。给予一次TCBT热解产物(300 mg/kg体重)会导致细胞色素P-450c依赖性反应(苯并(a)芘羟化酶、乙氧异吩恶唑酮O-脱乙基酶)显著增加。

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