伊维菌素对细胞色素P450同功酶活动的影响在欧洲盘羊(羊属musimon)和小鹿(Dama Dama)。

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Skalova L, Szotakova B, Machala M, Neca J, Soucek P, Havlasova J, Wsol V, Kridova L, Kvasnickova E, Lamka J

伊维菌素对细胞色素P450同功酶活动的影响在欧洲盘羊(羊属musimon)和小鹿(Dama Dama)。

化学生物相互作用。2001年8月31日,137 (2):155 - 67。doi: 10.1016 / s0009 - 2797 (01) 00227 - 7。

PubMed ID

11551531 (在PubMed

]

文摘

伊维菌素是一种抗寄生虫药物广泛应用于兽医和人类医学。早些时候我们发现,重复治疗的大鼠高剂量的这种药物导致显著增加细胞色素P450-dependent 7-methoxyresorufin O-demethylase (MROD)和7-ethoxyresorufin O-deethylase在肝微粒体(EROD)活动。在目前的研究中,伊维菌素对细胞色素P450 (CYP)活动的影响研究在欧洲盘羊(羊属musimon)和小鹿(Dama Dama)。该研究还指出普遍缺乏信息基底CYP酶水平和他们的可诱导性的兽药野生反刍动物。肝微粒体由控制动物,摩弗伦羊,后单或重复(6剂量连续六天)治疗与治疗剂量的伊维菌素(0.5毫克公斤体重的(1)),和小鹿暴露在相同的条件下重复剂量的伊维菌素。Alkyloxyresorufins,睾丸激素和chlorzoxazone被用作特定底物探针CYP同功酶的活动。单一的伊维菌素治疗剂量显著诱导(300 - 400%的对照组)所有的活动alkyloxyresorufin dealkylases测试摩弗伦羊肝微粒体。重复剂量的伊维菌素也增加了这些活动,但由于公平inter-individual差异,增加不显著。伊维菌素的管理导致感应(170 - 210%的控制)的睾丸激素6β,16α-羟化酶活动在摩弗伦羊肝,但没有明显的调制chlorzoxazone羟化酶(CZXOH)活动中发现摩弗伦羊肝。在肝微粒体CYP-dependent活动在小鹿一般都高于摩弗伦羊。 However, with the exception of slight increase in the 7-benzyloxyresorufin O-dealkylase (BROD) activities, no significant modulation of the other activities was observed. The induction of CYP3A-like isoenzyme was confirmed by immunoblotting only in the microsomes from mouflons administered with repeated doses of ivermectin; however, no significant increase of CYP1A isoenzymes was observed due to a weak cross-reactivity of anti-rat CYP1A1/2 polyclonal antibodies used in the study. The results indicate that ivermectin should be considered as an inducer of several cytochrome P450 isoenzymes, including CYP1A, 2B and 3A subfamilies, in mouflons. The comparison of induction effect of ivermectin in rat, mouflon and fallow deer also demonstrates the inter-species differences in inducibility of CYP enzymes.

DrugBank数据引用了这篇文章

药物酶

药物	酶	类	生物	药理作用	行动
伊维菌素	细胞色素P450 3 a4	蛋白质	人类	没有	底物	细节