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感染(胸膜肺炎放线杆菌)介导的猪肝脏氧化药物代谢及细胞色素P4503A mRNA水平的抑制

Infection (Actinobacillus pleuropneumoniae)-mediated suppression of oxidative hepatic drug metabolism and cytochrome P4503A mRNA levels in pigs.

作者信息

Monshouwer M, Witkamp R F, Nijmeijer S M, Van Leengoed L A, Verheijden J H, Van Miert A S

机构信息

Department of Veterinary Basic Sciences, University of Utrecht, The Netherlands.

出版信息

Drug Metab Dispos. 1995 Jan;23(1):44-7.

PMID:7720523
Abstract

The effect of Actinobacillus pleuropneumoniae infection, a well-characterized pig infection model, on both phase I (oxidative) and phase II (conjugative) microsomal enzyme activities was investigated in castrated male conventional pigs. A. pleuropneumoniae infection resulted after 24 hr in a significant suppression of 33% or more of all oxidative enzyme activities determined. After 40 hr, the activities were still suppressed, but did not differ from the results after 24 hr. On the contrary, all glucuronosyltransferase activities measured were not affected by A. pleuropneumoniae infection after both 24 and 40 hr. To elucidate further the mechanism of the suppression of oxidative enzyme activities, analysis of mRNA were conducted by dot-blot analysis using a human cytochrome P4503A4 cDNA probe. The results indicated that A. pleuropneumoniae infection suppressed oxidative enzyme activities. The reduction in cytochrome P4503A activity, specific for 6 beta-hydroxylation of testosterone is at a pretranslational level as measured by a decrease in the amount of mRNA.

摘要

在去势雄性普通猪中研究了胸膜肺炎放线杆菌感染(一种特征明确的猪感染模型)对I期(氧化)和II期(结合)微粒体酶活性的影响。胸膜肺炎放线杆菌感染24小时后,所测定的所有氧化酶活性均受到显著抑制,抑制率达33%或更高。40小时后,这些活性仍然受到抑制,但与24小时后的结果无差异。相反,在24小时和40小时后,所测定的所有葡萄糖醛酸转移酶活性均未受到胸膜肺炎放线杆菌感染的影响。为了进一步阐明氧化酶活性受抑制的机制,使用人细胞色素P4503A4 cDNA探针通过斑点印迹分析对mRNA进行了分析。结果表明,胸膜肺炎放线杆菌感染抑制了氧化酶活性。睾酮6β-羟基化特异性的细胞色素P4503A活性降低,通过mRNA量的减少测定,表明处于翻译前水平。

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