甲巯咪唑对硫代酰胺生物活化及毒性的影响。

The effect of methimazole on thioamide bioactivation and toxicity.

作者信息

Ruse M J, Waring R H

机构信息

School of Biochemistry, University of Birmingham, U.K.

出版信息

Toxicol Lett. 1991 Sep;58(1):37-41. doi: 10.1016/0378-4274(91)90188-c.

DOI:10.1016/0378-4274(91)90188-c

PMID:1832793

Abstract

The hepatotoxicity induced by administration of ethionamide and thionicotinamide (TNA) was shown to be decreased by pre-administration of methimazole (MMI). Pre-administration of MMI was also shown to decrease the levels of excretion of TNA S-oxide. This indicates that thioamide S-oxidation, mediated by the flavin-containing mono-oxygenase, may be linked to the initiation of hepatotoxicity induced by these thioamides. SK&F-525-A, the cytochrome P-450 inhibitor, did not affect either thioamide-induced toxicity or levels of excretion of TNA S-oxide; however, the role of the P-450 isoenzymes cannot be totally ruled out.

摘要

给予乙硫异烟胺和硫代烟酰胺（TNA）所诱导的肝毒性经预先给予甲巯咪唑（MMI）后显示降低。预先给予MMI还显示可降低TNA S-氧化物的排泄水平。这表明由含黄素单加氧酶介导的硫酰胺S-氧化可能与这些硫酰胺诱导的肝毒性的起始有关。细胞色素P-450抑制剂SK&F-525-A既不影响硫酰胺诱导的毒性，也不影响TNA S-氧化物的排泄水平；然而，P-450同工酶的作用不能完全排除。