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首页> 外文期刊>Journal of biochemical and molecular toxicology >Induction of drug metabolizing enzymes by 1,7-phenanthroline and oltipraz in mice is unrelated to Ah-responsiveness.
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Induction of drug metabolizing enzymes by 1,7-phenanthroline and oltipraz in mice is unrelated to Ah-responsiveness.

机译：1,7-菲咯啉和oltipraz在小鼠中诱导药物代谢酶与Ah反应无关。

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摘要

The protective effect of several classes of compounds against the toxic and neoplastic effects of xenobiotics has been attributed to the induction of noncytochrome P450 (P450) drug metabolizing enzymes. Glutathione S-transferases (GST), NAD(P)H: quinone oxidoreductase (QOR), and UDP-glucuronosyltransferases (UGT) play a prominent role in detoxification and can be induced by oltipraz and other N-heterocyclic compounds in rats. In contrast to the induction of these enzymes by aryl hydrocarbon (Ah)-receptor agonists, induction by oltipraz and 1,7-phenanthroline is not accompanied by CYP1A induction. This study investigated the induction of drug metabolizing enzymes following administration of oltipraz and 1,7-phenanthroline in four mouse strains (C57B6A-J, Frings x C57B6J, Frings, CF-1) exhibiting varying degrees of responsiveness to an Ah-receptor agonist. The relative Ah responsiveness was determined in all strains by the induction of hepatic Cypla after three daily doses of 3-methylcholanthrene (20 mg/kg). After treatment with 1,7-phenanthroline and oltipraz (150 mg/kg i.g.) daily for 3 days, all strains showed similar induction of GST and QOR activities for each inducer. Both compounds were equally effective in elevating GST activity, but 1,7-phenanthroline was more effective than oltipraz in elevating QOR activity. In addition to GST and QOR changes, 1,7-phenanthroline significantly elevated UGT (1-naphthol) activity in the Frings strain. Neither compound produced significant changes in Cypla parameters. The independence of 1,7-phenanthroline and oltipraz induction of GST and QOR from Cypla-responsiveness is in line with the concept that N-heterocycle-containing inducers act by mechanisms other than an Ah-receptor-dependent pathway in which the P450 response has been masked or prevented.
机译：几类化合物对异种生物的毒性和肿瘤作用的保护作用已归因于非细胞色素P450（P450）药物代谢酶的诱导。谷胱甘肽S-转移酶（GST），NAD（P）H：醌氧化还原酶（QOR）和UDP-葡糖醛酸糖基转移酶（UGT）在解毒中起着重要作用，并且可由大鼠oltipraz和其他N-杂环化合物诱导。与由芳烃（Ah）-受体激动剂诱导这些酶相反，由oltipraz和1,7-菲咯啉诱导不伴随CYP1A诱导。这项研究调查了在四只小鼠品系（C57B6A-J，Frings x C57B6J，Frings，CF-1）中施用oltipraz和1,7-菲咯啉后对药物代谢酶的诱导作用，这些菌株对Ah受体激动剂的反应程度不同。每天三剂3-甲基胆碱（20 mg / kg）后，通过诱导肝Cypla来确定所有菌株中的相对Ah反应。每天用1,7-菲咯啉和oltipraz（150 mg / kg i.g.）处理3天后，所有菌株对每种诱导剂均表现出相似的GST和QOR活性诱导。两种化合物在提高GST活性方面均同样有效，但1,7-菲咯啉在提高QOR活性方面比oltipraz更有效。除了GST和QOR的变化，Frings菌株中的1,7-菲咯啉还显着提高了UGT（1-萘酚）的活性。两种化合物均未产生Cypla参数的显着变化。 1，7-菲咯啉和吡虫啉对GST和QOR的诱导与Cypla反应无关，这与含有N杂环的诱导物通过除Ah受体依赖性途径（其中P450反应具有其他途径）以外的机制起作用的概念一致。被掩盖或预防。

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