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甲苯胺对大鼠肝脏、肾脏和肺脏中药物代谢酶的影响。

Effect of toluidines on drug metabolizing enzymes in rat liver, kidney and lung.

作者信息

Gnojkowski J, Baer-Dubowska W, Klimek D, Chmiel J

出版信息

Toxicology. 1984 Sep 28;32(4):335-42. doi: 10.1016/0300-483x(84)90085-4.

DOI:10.1016/0300-483x(84)90085-4
PMID:6435287
Abstract

The effect of pretreatment with o-, m- and p-toluidine on the drug-metabolizing enzymes of liver, kidney and lung in rats were investigated. The activities of microsomal aryl hydrocarbon hydroxylase (AHH), aminopyrine demethylase, NADPH-cytochrome c reductase, epoxide hydrolase, cytosolic glutathione S-transferase as well as the concentrations of cytochrome P-450 and cytochrome b5 were determined. The obtained results showed that o-toluidine increased the activity of AHH in all tested organs; a particularly marked increase was observed in the kidney. The activity of NADPH-cytochrome c reductase and the content of cytochrome b5 were enhanced by o-toluidine only in the liver. m-Toluidine enhanced the glutathione S-transferase activity while the p-isomer increased both the epoxide hydrolase and the glutathione S-transferase activities. p-Toluidine decreased the AHH and aminopyrine demethylase activities and the cytochrome P-450 content. These results may explain in part the previously reported observations on carcinogenic activity of o-toluidine.

摘要

研究了邻甲苯胺、间甲苯胺和对甲苯胺预处理对大鼠肝脏、肾脏和肺脏药物代谢酶的影响。测定了微粒体芳烃羟化酶(AHH)、氨基比林脱甲基酶、NADPH-细胞色素c还原酶、环氧化物水解酶、胞质谷胱甘肽S-转移酶的活性以及细胞色素P-450和细胞色素b5的浓度。所得结果表明,邻甲苯胺增加了所有受试器官中AHH的活性;在肾脏中观察到特别显著的增加。仅在肝脏中,邻甲苯胺增强了NADPH-细胞色素c还原酶的活性和细胞色素b5的含量。间甲苯胺增强了谷胱甘肽S-转移酶的活性,而对异构体增加了环氧化物水解酶和谷胱甘肽S-转移酶的活性。对甲苯胺降低了AHH和氨基比林脱甲基酶的活性以及细胞色素P-450的含量。这些结果可能部分解释了先前报道的关于邻甲苯胺致癌活性的观察结果。

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