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喹乙醇对雄性大鼠肾上腺中醛固酮、皮质酮及五种类固醇生成酶mRNA的长期剂量依赖性反应

Long-term dose-dependent response of Mequindox on aldosterone, corticosterone and five steroidogenic enzyme mRNAs in the adrenal of male rats.

作者信息

Huang Xian-Ju, Ihsan Awais, Wang Xu, Dai Meng-Hong, Wang Yu-Lian, Su Shi-Jia, Xue Xi-Juan, Yuan Zong-Hui

机构信息

National Reference Laboratory of Veterinary Drug Residues (HZAU), Huazhong Agriculture University, Wuhan 430070, PR China.

出版信息

Toxicol Lett. 2009 Dec 15;191(2-3):167-73. doi: 10.1016/j.toxlet.2009.08.021. Epub 2009 Sep 4.

Abstract

Mequindox (MEQ) is a synthetic quinoxaline 1,4-dioxides (QdNOs) derivative which can effectively improve growth and feed efficiency in animals. This study was to investigate the dose-dependent long-term toxicity in the adrenal of male rats exposed to 180 days of MEQ feed. Our data demonstrated that high doses of MEQ in the diet for 180 days led to adrenal damage and steroid hormone decrease, combined with sodium decrease and potassium increase in rat plasma. Significant changes of GSH and SOD in plasma were observed in the high doses (110, 275 mg/kg) groups. At the same doses, MEQ treatment down-regulated the mRNA levels of CYP11A1, CYP11B1 and CYP11B2 which located in mitochondria, but up-regulated mRNA levels of CYP21 and 3beta-HSD which located in endoplasmic reticulum. In conclusion, we reported the dose-dependent long-term toxicity of MEQ on adrenal gland in male rats, which raise awareness of its toxic effects to animals and consumers, and its mechanism may involve in oxidative stress and steroid hormone biosynthesis pathway.

摘要

喹乙醇(MEQ)是一种合成的喹喔啉-1,4-二氧化物(QdNOs)衍生物,能有效提高动物的生长性能和饲料效率。本研究旨在探讨雄性大鼠经180天MEQ饲料喂养后,其肾上腺的剂量依赖性长期毒性。我们的数据表明,高剂量MEQ饲料喂养180天会导致肾上腺损伤和类固醇激素减少,同时大鼠血浆中钠减少、钾增加。在高剂量(110、275mg/kg)组中观察到血浆中谷胱甘肽(GSH)和超氧化物歧化酶(SOD)有显著变化。在相同剂量下,MEQ处理下调了位于线粒体中的CYP11A1、CYP11B1和CYP11B2的mRNA水平,但上调了位于内质网中的CYP21和3β-羟基类固醇脱氢酶(3β-HSD)的mRNA水平。总之,我们报道了MEQ对雄性大鼠肾上腺的剂量依赖性长期毒性,这提高了人们对其对动物和消费者毒性作用的认识,其机制可能涉及氧化应激和类固醇激素生物合成途径。

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