Long-term dose-dependent response of Mequindox on aldosterone, corticosterone and five steroidogenic enzyme mRNAs in the adrenal of male rats.
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.
Huang
Xian-Ju
XJ
National Reference Laboratory of Veterinary Drug Residues (HZAU), Huazhong Agriculture University, Wuhan 430070, PR China. huangxj554@sohu.com
Ihsan
Awais
A
Wang
Xu
X
Dai
Meng-Hong
MH
Wang
Yu-Lian
YL
Su
Shi-Jia
SJ
Xue
Xi-Juan
XJ
Yuan
Zong-Hui
ZH
D000307:Adrenal Gland Diseases / Q000139:chemically induced / Q000473:pathology; D000311:Adrenal Glands / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013256:Steroids / Q000096:biosynthesis*; D013482:Superoxide Dismutase / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000187:drug effects
C545385:Mequindox; D011810:Quinoxalines; D012333:RNA, Messenger; D013256:Steroids; D000450:Aldosterone; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D005978:Glutathione; D003345:Corticosterone