4.5 Article

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

Journal

TOXICOLOGY LETTERS
Volume 191, Issue 2-3, Pages 167-173

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2009.08.021

Keywords

Mequindox; Aldosterone; Corticosterone; CYPs; Adrenal

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Funding

  1. National Basic Research Program of China [2009CB118800]
  2. China Postdoctoral Science Foundation [20080440949]

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Mequindox (MEQ) is a synthetic quinoxalme 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 3 beta-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. (C) 2009 Elsevier Ireland Ltd All rights reserved.

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