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链球菌溶血素O、沙培林(OK 432)及干扰素α 2A对大鼠肝脏中细胞色素P - 450依赖性单加氧酶和芳胺N - 乙酰基转移酶的影响。

Effects of streptolysin O, picibanil (OK 432) and interferon alpha 2A on cytochrome P-450-dependent monooxygenases and arylamine N-acetyltransferase in rat liver.

作者信息

Hadasová E, Siegmund W, Walter R, Scheuch E, Franke G

机构信息

Department of Pharmacology, Medical Faculty, Masaryk University, Czech Republic.

出版信息

Immunopharmacol Immunotoxicol. 1995 May;17(2):283-300. doi: 10.3109/08923979509019751.

DOI:10.3109/08923979509019751
PMID:7650291
Abstract

Streptolysin O, a thiol-activated exotoxin from group A beta-haemolytic streptococci, caused a dose-dependent depression of aniline hydroxylase, aminopyrine N-demethylase and ethylmorphine N-demethylase activities when added into the hepatic microsomal mixtures from male rats at concentrations 0.02-0.4 HU/mL in vitro. The activities of 7-ethoxycoumarin O-deethylase, 7-ethylresorufin O-deethylase and 7-pentylresorufin O-depentylase were not altered with the used concentrations of the toxin. Specific antibody against haemolytic action of streptolysin O added to incubation mixtures in vitro was not able to protect streptolysin-sensitive monooxygenases from the inhibition. The addition of streptolysin O (0.01-0.8 HU/mL) into the cytosol-containing medium did not significantly influence the activity of procainamide N-acetyltransferase. Immunomodulators picibanil (OK 432) and human recombinant interferon alpha 2A which are known to suppress oxidative metabolism in vivo in humans and animals, were without effect either on the cytochrome P-450-dependent monooxygenases or on the N-acetyltransferase activity when administered in vitro at the doses real in their clinical application (0.001-0.1 KE/mL of picibanil and 10-500 U/mL of alpha-interferon).

摘要

链球菌溶血素O是一种来自A组β溶血性链球菌的硫醇激活外毒素,当以0.02 - 0.4 HU/mL的浓度在体外添加到雄性大鼠的肝微粒体混合物中时,它会导致苯胺羟化酶、氨基比林N - 脱甲基酶和乙基吗啡N - 脱甲基酶的活性呈剂量依赖性降低。在所使用的毒素浓度下,7 - 乙氧基香豆素O - 脱乙基酶、7 - 乙基试卤灵O - 脱乙基酶和7 - 戊基试卤灵O - 脱戊基酶的活性没有改变。在体外孵育混合物中添加针对链球菌溶血素O溶血作用的特异性抗体,无法保护对链球菌溶血素敏感的单加氧酶免受抑制。将链球菌溶血素O(0.01 - 0.8 HU/mL)添加到含有胞质溶胶的培养基中,对普鲁卡因酰胺N - 乙酰转移酶的活性没有显著影响。免疫调节剂沙培林(OK 432)和人重组干扰素α2A在体内已知可抑制人和动物的氧化代谢,当以其临床应用中的实际剂量(0.001 - 0.1 KE/mL的沙培林和10 - 500 U/mL的α干扰素)在体外给药时,对细胞色素P - 450依赖性单加氧酶或N - 乙酰转移酶活性均无影响。

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